Zhou Xuedong


Dental Caries
Principles and


Dental Caries

Zhou Xuedong Editor Dental Caries Principles and Management .

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. . . . . . . . . . . . . . . . Xu Hockin H. . . . Wang Shuang. . . . .Contents 1 Tooth Development: Embryology of the Craniofacial Tissues . . . . . . 91 Hong Xiao 7 Clinical Management of Dental Caries . Liu Yaling. . . . . . . . . Shi Wenyuan. . . . . . . Li Yuqing. . . . . . . . . . . . . . . . . . . . . . . . and Zhou Xuedong 5 The Diagnosis for Caries . . . . . . . . . . . . . Zhou Yuan. . . . . 157 Huang Xuelian. . . Zhang Yaru. . . . . . . . Guo Qiang. . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . .K. . . . . Li Jiyao. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Ren Biao. . . . and Zhou Xuedong 3 Saliva and Dental Caries . . . . . . 59 Wang Renke 4 Demineralization and Remineralization . 71 Cheng Lei. . . . . . . . . . . . . . . . . . . and Peng Li 6 Dental Caries: Disease Burden Versus Its Prevention . . . . . . . . . . . . and Ye Ling 2 Biofilm and Dental Caries . . . . 175 v . 85 Yang Liu. 107 Li Jiyao 8 Dental Caries and Systemic Diseases . . . . . . . . . . Li Boer. . . . . . . . . and Zhou Xuedong Index . . . . . . . . 27 Xu Xin. . . . . . . . 129 Zou Ling and Hu Tao 9 Models in Caries Research . . . . . . . . . Wang Chenglin. . . . . . . . . . . . . . . . . 1 Zheng Liwei. . . .


People’s Republic of China Wang Chenglin State Key Laboratory of Oral Diseases. University of Maryland Dental School.Contributors Ren Biao State Key Laboratory of Oral Diseases. People’s Republic of China Cheng Lei State Key Laboratory of Oral Diseases. Sichuan University. Chengdu. Chengdu. Chengdu. West China Hospital of Stomatology. China Zou Ling Department of Conservation Dentistry and Endodontics. Chengdu. People’s Republic of China Li Boer State Key Laboratory of Oral Diseases. Sichuan University. West China Hospital of Stomatology. Sichuan University. Sichuan University. West China Hospital of Stomatology. China Xu Hockin H. Chengdu. Sichuan University. Chengdu. Biomaterials & Tissue Engineering Division. Baltimore. Sichuan University. USA Li Jiyao State Key Laboratory of Oral Diseases. Sichuan University. Chengdu. West China Hospital of Stomatology. Chengdu. West China Hospital of Stomatology. Department of Endodontics. West China Hospital of Stomatology. K. Sichuan University. People’s Republic of China Ye Ling State Key Laboratory of Oral Diseases. Sichuan University. Chengdu. People’s Republic of China vii . People’s Republic of China Department of Operative Dentistry and Endodontics. West China Hospital of Stomatology. People’s Republic of China Peng Li State Key Laboratory of Oral Diseases. Sichuan University. People’s Republic of China Department of Operative Dentistry and Endodontics. Chengdu. West China Hospital of Stomatology. Sichuan University. MD. Prosthodontics and Operative Dentistry. Chengdu. People’s Republic of China Yang Liu State Key Laboratory of Oral Diseases.

Chengdu. Sichuan University. Los Angeles. People’s Republic of China Huang Xuelian State Key Laboratory of Oral Diseases. People’s Republic of China Zhou Yuan State Key Laboratory of Oral Diseases. Chengdu. West China Hospital of Stomatology. Sichuan University. People’s Republic of China Department of Oral Biology. Sichuan University. Chengdu. China Guo Qiang State Key Laboratory of Oral Diseases. Sichuan University. People’s Republic of China . Sichuan University. FL. Sichuan University. People’s Republic of China Department of Operative Dentistry and Endodontics. Sichuan University. USA Hong Xiao Department of Preventive Dentistry. West China Hospital of Stomatology. West China Hospital of Stomatology. West China Hospital of Stomatology. University of Florida. People’s Republic of China Zhou Xuedong State Key Laboratory of Oral Diseases. Chengdu. Chengdu. Sichuan University.viii Contributors Zheng Liwei State Key Laboratory of Oral Diseases. Sichuan University. People’s Republic of China Department of Operative Dentistry and Endodontics. Chengdu. Chengdu. Chengdu. Chengdu. USA Zhang Yaru State Key Laboratory of Oral Diseases. Chengdu. West China Hospital of Stomatology. China Xu Xin State Key Laboratory of Oral Diseases. West China Hospital of Stomatology. Sichuan University. CA. People’s Republic of China Li Yuqing State Key Laboratory of Oral Diseases. People’s Republic of China Wang Shuang State Key Laboratory of Oral Diseases. Chengdu. Chengdu. West China Hospital of Stomatology. Sichuan University. West China Hospital of Stomatology. Chengdu. People’s Republic of China Hu Tao Department of Preventive Dentistry. People’s Republic of China Wang Renke West China Hospital of Stomatology. Sichuan University. Sichuan University. West China Hospital of Stomatology. University of California-Los Angeles. Chengdu. West China Hospital of Stomatology. People’s Republic of China Shi Wenyuan School of Dentistry. Sichuan University. Chengdu. Gainesville. Sichuan University. West China Hospital of Stomatology. College of Dentistry. China Liu Yaling State Key Laboratory of Oral Diseases.

1. which is the fusion of spermatozoa and ova to Next. © Springer-Verlag Berlin Heidelberg 2016 1 Z. Liwei • W. The embryonic disk becomes the the proliferative 2-week period. ectodermal layer. which is termed “proliferative period” [1]. Implantation takes place. China These folds in turn encompass and fuse so that neu- e-mail: zhenglw399@hotmail.2 The Neural Crest The nervous system begins with a specification of the neural plate. which will extends from the second to the eighth weeks. A small disk (the embryonic human prenatal development. including oral form a zygote. Wang Chenglin.com ral tube forms and separates from the ectoderm. when cell divi.1007/978-3-662-47450-1_1 . West China the neural plate develops raised folds at its margins. and form the outer body covering (epithelium). allowing 1. Hospital of Stomatology. Ling (*) within the anterior ectodermal layer. meanwhile. two small The development of craniofacial tissues is part of cavities are formed. called the fetal period. which develops as a thickening Z. On either side of the inner cell mass. One sion is prevalent.). uterine endometrium is digested. Chengdu. DOI 10. Generally. Then the zygote moves to the uter. and Ye Ling 1. the embryonic period. State Key Laboratory of Oral Diseases. embryo. the uterus and. two-layered embryonic 1. When this blastocyst attaches to the sticky wall of the body of the uterus. and folding of the embryo.1. This configuration is completed in the first 2 weeks.1 Origin of Human Tissue disk is converted to a three-layered disk. dermal layers become the mesodermal layer. human body forms stepwise. major tissues and organs. and the ectoderm. which layer is lined with ectodermal cells. differentiate from these three layers [2]. 610041 Sichuan. Dental Caries: Principles and Management. composed of two layers of cells. where they reach prenatal development goes through three stages: each other. human disk) develops in the center.1 Embryology blastocyst embedded in its surface and then of the Craniofacial Tissues deeper penetration. During the third week. Cells that develop between the ectodermal and endo- The origin of tissue begins with fertilization. maxillofacial tissue such as tooth and facial ine cavity where it will implant into the wall of bones. small inner cell mass. Xuedong (ed. Sichuan University. from eighth week to birth [1]. Meanwhile. termed blastocyst. The cells on the ventral aspect With normal accomplishment of the develop. undergoes a series of Key events are the development of the nervous rapid divisions that lead to the formation of a system. are endodermal cells. Chenglin • Y. Tooth Development: Embryology of the Craniofacial Tissues 1 Zheng Liwei. differentiation of neural crest tissue from fluid filled hollow ball. layer. forming the endodermal ment.

2. the head and neck region. can be distinguished from the round inter- endoderm. dentin. which is in contact with sev- ral crest. and neural crest cells have an important role in the head development. shape development.1). Experiment approaches sug- gested that Wnt/Shh interactions may regulate the delimitation between the dental epithelium and 1. Although the neural occurs in the early tooth initiation.2 Z.1 Histogenesis tive tissue of facial region. his- and differentiation. 1. This chapter will provide a population of cells known as neural crest cells brief overview in different aspects of tooth enamel separate from the lateral aspect of the neural development with a particular emphasis on the plate.1. embryonic connective tissue in the The consecutive phases during tooth morphologic head is termed as ectomesenchyme. and cementum. When the stomatodeum first forms. Nevertheless. They contribute to most of the embryonic connec. they cates that a local epithelial thickening corresponds exhibit properties of mesenchyme [2. Liwei et al. cells are evident in changes of the expression of Laterally the somatodeum becomes delimited by different molecules.3 Head Formation the oral ectoderm. which forms the basal epithe- a bilaminar structure consisting of ectoderm and lium. The histogenesis of the crystal initiation. ing teeth. lia. cap. and cytodifferentiation. whereas connective tis. 1. including γ-catenin. as well as mor. in the composition of the basement membrane. are characterized by epithelial histogene- sue elsewhere is derived from the mesoderm and sis. And it is separated From the bud stage. to the dental lamina. the round cells. oral cavity. crystal growth. both with primary enamel knot. including lamina. internal differentiation of the tooth-specific cell types. 1. which indi- crest tissues arise from neural ectoderm. Upon closure of the neural tube. The mechanisms of outer enamel epithelium. and survival or compartmentalization of different cial and produces the primitive stomatodeum or elements is still poorly understood (Fig. enamel epithelium becomes discernible from the apatite crystals. and P. it is surrounded by frontal prominence rostrally and 1. and bell origin from the ectoderm. Depending on the position.1. the stellate reticulum. including peripheral cells. the thickened presumptive from the foregut by buccopharyngeal membrane.and E-cadherins.1 Bud Stage by the cardiac bulge caudally. At this time.2 Enamel Development During the cap stage. a unique epithelial ameloblasts. inner dental epithelium is coordinated by a change phology are related to amelogenesis. The segmentation of the dental epithelium is known as mesenchyme. glein. These cells have the capability of migration current knowledge of enamel morphogenesis. The head fold of the three-layered embryo is cru. stages.1. This is especially obvious in togenesis. 3]. which breaks down soon so that the nal cells. epithelial stomatodeum communicates with the foregut. reflecting its changes.2. the dental epithelium becomes the enamel organ which consists of four Fully mature enamel comprises 80–90 % (v/v) different cell types: inner and outer dental epithe- carbonated calcium hydroxyapatite crystals. desmo- the first pair of pharyngeal arches [1. as well as transiently the which is in contrast to bone and dentin. and basement membrane cells. which derive from the cranial neu. dental epithelium. In develop. bud. Consequently. the molecules intervene in regulating epithelial cell apoptosis.2. sequential and reciprocal interactions The enamel knot is a dynamic transient struc- occur between the epithelium and the underlying ture and appears at the onset of mammalian tooth mesenchyme. Enamel formation associates with the eral cells. which includes dental and Morphogenesis tissues such as the pulp. . the inner 10 % and 13 % (v/v) carbonated calcium hydroxy. respectively.2 Cap Stage 1. 2].

the pri. From the lamina stage to the bell stage. changes mary enamel knot starts to extend in anterior and in reorganization of the epithelium compartment posterior directions. known as presecretory. ary enamel knots. by a reaction–diffusion-related mechanism. cap stage. The first step creates partially mouse strains or measuring stages of embryos. mineralized enamel (about 30 %). the programmed cell death is also accompanied It has been suggested that the structure and by the regulation of cell number in the inner den- organization of primary enamel knot rapidly tal epithelium. secretory. The dif- dental papilla and starts to form cusps. consists mechanism is still not known due to differences in of two main steps. the underlying Amelogenesis. and secretion of of the forming cusps at the bell stage.2 Cytodifferentiation internal cells begin apoptosis. some of 1. The that occur in time and involve growth. suggesting its role in determining change during the time.2. zation of inner dental epithelium. polarization. These epithelial cells exhibit a tionship between primary and secondary enamel unique character of progressively changed pheno- knots has been suggested in several models. which loblast cells includes several morphologic changes only precede cusp formation by a few hours. represents a signaling center in formatting cusps. within the enamel organ. the shape of the crown is determined.2. The second step involves extreme influx of additional mineral 1.2). The growth which may lead to unequal growth of the enamel of crown results from cell division and reorgani- epithelium and induce the formation of second. elongation secondary enamel knots are taken place at the tips of the cytoplasm. it appears as a long cylindrical shape and the shape will extend along the mesial–distal axis of the first lower molar. Furthermore.1. However.3 Bell Stage while removing organic material and water to At the bell stage. or enamel formation. Amelogenesis has been described in as gene expression patterns elucidated the primary many as six stages but generally is divided into enamel knot induces the secondary enamel knots three functional phases. At the beginning of the the final number of functional ameloblast cells. the secondary enamel knots form. matrix protein. . The type. At this ferentiation of epithelial cells into functional ame- time. Soon after. They not only regulate his- primary enamel knot. The rela. It is suggested that in the can be distinguished.1 Tooth Development: Embryology of the Craniofacial Tissues 3 a b c d Fig. 1. most cells do not divide and togenesis but also determine the final number and its proliferation needs the recruitment of cells specific positioning of functional ameloblasts. While the first lower molar grows during cap formation. the enamel organ delimitates the form more than 96 % mineral contents. and maturation stages (Fig.1 (a–d) Morphogenesis of the tooth development (from bud to bell stage) Studies indicated that the primary enamel knot During the bell stage of tooth development. 1.

2. During the secretory Golgi elements increase and migrate distally. compartmentalizing the plex is intense and forms a cylindrical organelle ameloblast cells into a body and a distal exten. At this time.2. a sec. The fine structure of secretion of enamel proteins.2. the cytoplasm becomes filled with polarized morphology and secrete an extracellu- organelles which are needed for the synthesis and lar protein-rich matrix. Fig. the cells of the plex or attachment specializations [2]. genesis determine what may pass between cells to inner enamel epithelium cells are cuboidal or low enter or leave the enamel at different times. surrounded by many cisternae of rough endoplas- sion called Tomes’ process. Liwei et al. The Golgi com- extremity of the cell.4 Z. Ameloblast cells are aligned closely of the process against the newly formed mantle . Tomes’ pro- secretion starts much earlier. against which enamel mic reticulum. columnar. and the rodless enamel matrix. these cells elongate. At the morphogenetic phase. The aration between pre-ameloblasts and pre. once The newly formed ameloblasts near the dental stimulated. During differentiation phase. researches demonstrate that the enamel protein When enamel formation begins. which means the secretion is successively. 1. cess comprises only a proximal portion.1 Presecretory Stage with each other due to the tight junctional com- During the presecretory phase. Although the pre-ameloblasts have been and the secretory granules are not stored for pro- regarded as nonsecreting cells. tive. stage. Ameloblast secretion is constitu- develops. These inner enamel epithelium start to differentiate into junctional complexes greatly involved in amelo- ameloblast cells. secretory granules are released along the surface odontoblasts. even before the sep. their nuclei shift papilla are flat and the matrix secreted is called distally toward the stratum intermedium. the ameloblasts exhibit a tall columnar and Moreover.2.2 Secretory Stage of the cells. secretory stage ameloblasts indicated their strong ond junctional complex forms at the distal synthetic and secretory activity. more and more longed periods of time. with large centrally located nuclei and poorly formed organelles in the proximal portion 1.2 Ameloblast differentiation 1.

eventually forming the enamel. Finally. Enamel rods cross one It is believed that the stratum intermedium another and follow an undulating course as they cells are also related to secretory and absorptive progress from the DEJ toward the enamel surface. stop- ameloblast cells undergo several morphologic ping at the final layer of aprismatic enamel [4].2. 1. The enamel rods run nearly After immature enamel has fully formed. the initial. morphologic and functional changes. indeed. phases of proliferation. Following plex to the enamel layer surface [2]. at resorbing much of the water and organic matrix from the enamel in order to allow enough space 1. At without enamel rods. ameloblasts It is believed that the distal portion of Tomes’ deposit enamel in the form of rods or prisms that process progressively lengthens as the enamel become highly mineralized. form a continuum [2]. the ameloblasts aim other [7] (Fig. differentiation. The very first hydroxyapatite this time. blasts and Tomes’ process. the deposition of a layer of enamel. Notably. This change Using the scanning electron microscope and fol- results from the thickness and width growth of lowing a short etching part. some ameloblast cells undergo form the distal portion of Tomes’ process as an programmed apoptosis. the enamel consists of highly crystal- line nanorod-like calcium hydroxyl apatite crys- 1. The arrangement of layer thickens and gradually turns to be thinner as ameloblasts with their Tomes’ process plays a the rod developing in diameter presses it against critical role in the formation of enamel rods.3). perpendicular to all parts of tooth surface. between the enamel rod and interrod enamel. incisal or cuspal order.3. dur- crystals formed interdigitate with the dentin crys. At the loblast cells migrate from the dentin surface and maturation stage. roughly about half of the outgrowth of the proximal portion. nanoscale. When the outer layer of enamel is being formed. the of mineral and organic phases. with stratum intermedium cells appear less active as the convex surface of the arcades oriented in an enamel maturation is near completion [4]. 6]. leading to slightly dif- ference of enamel rods in the outer third of layer The enamel is a composite structure consisting with a more rectilinear trajectory.1 Enamel Rod for the growing enamel crystals [2]. ameloblasts arise from the inner initial layer of enamel. When the arcades connect to each other.3 Microstructure of the Enamel orientation also changed. interrod. enamel epithelial cells and experience multiple tion penetrates from the distal junctional com. while the proximal por. The the wall of the interrod cavity. row area which is filled with organic materials and maturation. The distal ameloblasts is reduced during amelogenesis. After forming the initial enamel layer. a short transitional stage appears. The enamel formative stage. secretion. the final enamel and surface features [5. On the tory surface and. and the enamel consists of highly organized architec- final enamels are developed by the same secre.2.1 Tooth Development: Embryology of the Craniofacial Tissues 5 dentin to create an initial layer of the enamel changes in preparing maturing the enamel. the distal portion of Tomes’ process is altered and 1.3 Maturation Stage tallites that are arranged roughly parallel to each During the maturation stage. enamel rods can be preexisting crystals seeded during amelogenesis observed in ground or fractured teeth. volume and organelle content decrease. enamel itate their close contact with ameloblast cells. ame. Eventually. the process of amelogenesis is a series of successive process is squeezed out of existent. not due to additional crystal rod represents the mineralized progress of amelo- accumulation. On the microscale. At the nanometer ameloblasts become the same overall appearance scale.2. portion extends into and interdigitates beyond the In summary. ing which ameloblasts become shorter and their tals. dental enamel has hierarchical structures distal portion of Tomes’ process. The rods have the features of keyholes or paddles. leaving a nar. like most other naturally mineralized tis- as when initial enamel was forming. tural units known as enamel prisms. functions of amelogenesis and desmosomes facil. Without the sues. has no rods.2. .

The compara- enamel is formed.3.3.6 Z.2 Enamel Spindle 1. to be removed.2.6 Functional Aspects of Enamel section and usually appear as artifacts during Structure teeth processing. which enamel of the enamel rod.2. It has a microporous structure. The secretory product is released from the ame- entiation stage of amelogenesis.4 Enamel Tufts parallel formation of crystals perpendicular to the Enamel tufts originate from the DEJ and extend surface of the teeth brings about the best way for 1/3 to 1/2 of the thickness of the enamel matrix. The second 1. Although single crystal is too . building open-sided and exhibit vertical orientation from incisal or prism boundaries. In many circum- enamel. When the initial loblast cells at two preferred sites.3. The 1. the need to nucleate new crystals during enamel ment and also during the elaboration of the initial maturation. allows extra mineral flow in the crystals for fur- rich regions that failed to mature in the enamel ther growth while degrading matrix components matrix. 1.3 Enamel structures 1.5 Interpit Continuum Enamel spindles are generated during the differ. cuspal regions to cervical area. the enamel spindles become tively superficial site forms the majority parts of terminal extensions of the primary dentinal all developing enamel surfaces.3. The particular organization of the enamel serves as enhancing hardness and wear resistance.2. lamellae include thin sheets of organic materials crystals may have orientations that merge with that extend throughout the enamel mineralization those from the interpit stage. the interpit phase is continuous through- out vast parts of the tissue [8]. At these sites. Spindles exhibit ameloblastic and the product determines pits.2. stances. Enamel which aims at filling in the pit. Liwei et al. dense packing of the crystals as well as obviates They are formed during Tomes’ process develop.3 Enamel Lamellae and Cracks location at which the enamel matrix is released is It is believed that enamel lamellae are the result from the secretory pole of Tomes’ process proper.3. of local failure of the maturation process. They represent protein. Fig.2. This site is inter- tubule into the enamel matrix. bulbous structures at DEJ region in mature tooth naming interpit for this stage. Cracks share some similar characters with lamellae in ground 1.

secreting. amelogenin protein secretion. proline. pal variation of sequence homology occurring ing that the disruption of synthesizing. allowing ing an autosomal-dominant AI phenotype [13]. such as elastin. 1. Studies provide functional data show. The initial enamel layer is dominated by Enamel formation requires a remarkable orches. amino-terminal. During in vivo enamel feature of enamelin proteins has been reported to formation. 20].2. the amelogenin nanosphere also can be be in line with its capability to bind to enamel observed adjacent to HAP crystallites [21]. amelogenin genes have 7 exons. . indicating amelogenin proteins play a phenotype are associated with aberrations of major role in the regulation of enamel thickness enamel. broken tips of incisors enamel developing and maturing stages [10].2. teins of those two AIH1 point mutations have been tein that has been postulated to play an essential compared with wild-type amelogenin. In human. The mutations mineral component. absent. Several studies have and organization of crystal pattern [24] (Fig. Enamel crystals are the largest crystals found and easily abraded [10]. within exon 6. The recombinant pro- [10.4. nization and mineralization. including amelogenin. Enamelin is a novel acidic enamel pro. Human enamelin. tyrosine-rich amelogenin peptide tin–enamel junction (DEJ) region is enamelin (TRAP) segment [17. In the crystals form into larger domains to be stron. causing AIH2. 18]. the perpendicular positions enable the described the mutations of enamelin gene caus- growth of long whisker-like crystals. tuftelin.2 Amelogenin involved in maintaining structural properties of The amelogenin proteins of developing dental enamel. The crust over the dentin is thin. the enamel layer is completely ger and stiffer. The and molars. the tration of diverse and essential enamel-secreted amelogenin gene has been shown to be located proteins.1 Enamelin Two human pedigrees with an X-linked AI (AIH1) A number of studies have suggested that the first phenotype both share the same mutation in the protein to be secreted by ameloblasts at the den. Enamelin is rich It has been found that human-inherited enamel in aspartic acid and could be arranged in β-sheet defect AI often associates with alterations in ame- conformation that results in nucleation of the logenin X chromosome gene [22]. the supramolecular assembly of amelo- sition and maturation [9].4). in amelogenin are known to hypoplastic or hypo- The enamelin proteins initially secreted at the mineralized enamel [22. appear as a functional structural protein during enamel formation [16]. ameloblastin.2. spheres. which codes for most amelogenin and processing these genes can cause different core and the C-terminus [15]. which is formed by the secre. indi. Enam−/− mice. 11]. dentin sialoprotein. on both X and Y chromosomes [14]. ame- 1. with the princi- and apin. the acidic assembly kinetics [19. exhibiting role in enamel mineralization. By high-resolution altered nanosphere dimensions and amelogenin protein-A gold immunocytochemistry. and glutamyl residues. mineral crystallite surfaces [12].4 Enamel Matrix Proteins logenin is the most abundant extracellular pro- tein. These analyses indicate in the body. irregular. histidine.1 Tooth Development: Embryology of the Craniofacial Tissues 7 flexible. Among all the ameloblast-specific proteins. The orientation of crystals and the distribution of organic matrix are 1. It has been shown that the amelogenin nano- cating the indispensable role for enamel compo. subtypes of amelogenesis imperfecta (AI). enamel are tissue-specific components. tory activity of ameloblasts. genin. as well as disorganized hypoplastic mutations of enamelin such as enamelin-null enamel. The primary structural unit of enamel that enamelin is essential for enamel matrix orga- is the enamel rod. 1. rich in leucine. amelotin. 23]. Amelogenin knock- very early phase of enamel formation are strictly out mice also display abnormal teeth with expressed by ameloblasts and persist throughout chalky-white discoloration.4.

resume pro. expressed by secretory ameloblasts.4 Immunostaining of amelogenin 1. 1. tein.5 Tuftelin enamel organ influences enamel crystallite habit Shortly after differentiation. Less bution following the ameloblast cell outline information is available describing whether or appears to be a ‘fishnet’-like partitioning [27]. by binding to ameloblasts dramatic increase from secretory to maturation and by inhibiting their proliferation [26]. and lose polarity. the cells are 9 exons and 8 introns and are located on chromo- detached from the underlying matrix. these data localizes to chromosome 1q21 in human. In secre- all suggest that in the enamel matrix. toward the zone of reduced ameloblast cells. is synthesized and secreted. reversing to undiffer. respectively. Liwei et al. enamelysin) and kallikrein-4 molars. other than the Golgi complex and secretes granules ation sites within the enamel (Fig.4. resulting in a pheno. experiencing a at the secretory stage. It has also demonstrated and then to Tomes’ processes [29]. indicating that ameloblastin expression of amelotin mRNA is essentially lim- maintains the differentiation state of ameloblasts ited in postsecretory ameloblasts. enamel matrix serine proteinase-1.4. Tuftelin gene type characteristic of AI. which are close liferation. The entiated one.8 Z. ine proteinase 17). 1. somes 5 and 4q13. ameloblastin distri. an acidic pro- and enamel rod morphology. Both murine and human amelotin genes contain tal epithelium initial differentiation. phase ameloblasts and subsequently lessening At secretory amelogenesis. and overexpression of ameloblastin in the 1.4 Amelotin 1. However. . expression of amelotin mRNA was (KLK4.6 Proteolytic Enzymes Murine amelotin has been identified recently. either gain of tory stage.2. a cell adhesion molecule.5 Immunostaining of ameloblastin the unique tooth-specific proteins. or ser- restricted to maturation-stage ameloblasts [28]. tuftelin.4. 1. that ameloblastin acts as a nucleator of crystalliza.3. Fig. ameloblastin null mice reveal severe enamel hypo- plasia. There are two major proteinases secreted into the which is the newest described enamel-specific enamel matrix.2.2. to the enamelin and ameloblastin genes.4. 1.2. the secretory pathway of amelogenin to function or loss of function of ameloblastin can the extracellular space is from the Golgi complex cause enamel alterations. in vivo tuftelin accumulates in cytoplasmic area tion because it is expressed at mineralization initi. Shortly after den. Undoubtedly. is one of Fig. in both mineralizing and nonmineralizing tissues. yet the expression decreases during enamel maturation [25]. including matrix metalloprotein- protein.3 Ameloblastin Ameloblastin. The not amelotin is a candidate gene for AI. In developing murine incisors and ase-20 (MMP20.5).

The elasticity of dentin In a mature tooth. most family that had a mutation in the intron 6 splice attentions are focused on the common themes acceptor [13]. ered in the teeth. and soft enamel.1 Dentin toblasts and late-secretory and maturation phase ameloblasts [31]. KLK4 mutation was found in a accounts for 20 % of dentin. their postulated roles in the biomineralization of tle. dentin is a unique. inorganic prostate. The a minor component of type V. and homeostasis of differentiated and undifferen- tiated or stem cell populations can be translated to Kallikrein-4 Human KLK4 gene is located on regenerative approaches targeted at restoring the chromosome 19q13.3. thus indicating it is nec. only the teeth were apparently matter makes up 45 % of dentin. and the theories about the development less radiodense. whose cells migrate from is the presence of tubules. particularly the synthesis and tern [30]. avascular provides flexibility for the overlying brittle enamel. complex.3 Pulpodentin Complex of intact dentin. acidic glycoproteins. 1. it is not sure whether KLK4 has an effect on the growth factors. the homozygous MMP20 secretion of extracellular matrix molecules and mutation family reveals severely pigmented. Organic matrix mineralization. including odon. In porcine teeth. KLK4 was first discov. KLK4 expression during Fully mature dentin is composed of approximately enamel maturation correlates with the degrada. so proteins (Gla-proteins). Dentin and pulp are derived Dentinal Tubules The characteristic of dentin from the dental papilla. In addition. both ameloblast about odontoblast differentiation that have and odontoblast cells express MMP20. while organic altered by the homozygous KLK4 mutation [23]. the affected members are all females. These tubules house the major cell processes of odontoblasts. The mutation of pulpodentin complex.1. molecules and water 33 % and 22 %.1 Structure of Dentin vated and highly vascularized soft connective tis- sue. which host the major the cranial neural crest. In the teeth. Tubules form . During emerged and what is known about the influence of the early stage of enamel formation. respectively. 1. matrix formation. By volume. which is characterized by dentin. KLK4 is secreted by different cell types. The human MMP20 is located on most commonly referred to as the “pulpodentin chromosome 11q22. the dental pulp. tion of enamel proteins. mineralized connective tissue that forms the bulk of the tooth.3.1 Tooth Development: Embryology of the Craniofacial Tissues 9 Matrix Metalloproteinase-20 Human MMP20 closely associated during development and gene consists of 10 exons and is part of the MMP throughout the life of an adult tooth and are hence gene clusters. MMP20 tooth-signaling molecules and transcription fac- activity accounts for virtually all of the known tors on the development and homeostasis of the cleavage sites in amelogenin.” recessive form of AI was recently discovered in a During the process of tooth development. 91 % of organic matrix family with autosomal recessive hypomaturation is collagen. Noncollagenous enamel fractured from the teeth has normal thick. and lipids. The tissues remain cell processes of odontoblasts. and an autosomal.3. The principal inorganic component consists of essary for the enamel to achieve the high level of Ca10(PO4)6(OH)2 (hydroxyapatite). the focus is the MMP20 exhibits hypoplastic enamel with theories about the general principles of dentin improperly processed amelogenin and rod pat. A characteristic of human dentin is the presence of tubules that occupy from 20 to 30 % of the volume 1. teoglycans. 70 % inorganic material and 10 % water by weight. showing yellow-brown discolored teeth. pro- ness but with a decreased mineral content. In addition.41. gamma-carboxyglutamate-containing Notably. integrity of the adult pulpodentin complex. brit. with AI. and dentin encloses a richly inner. but it also expressed in other tissues such as the prostate. and most of the collagen is type I. matrix components include phosphoproteins. However.

dogs. the tubules converge because the sur. their processes and constitutes the bulk of circumpulpal dentin. 1. Intertubular Dentin Intertubular dentin is eral cytoplasmic processes toward the DEJ. Its organic matrix consists mainly of collagen . which leads to a con. 1. This (Fig. fact that during the initial stage of dentinogene- sis. Peritubular Dentin Dentin lining the tubules is verse the entire width of the dentin from the DEJ termed peritubular dentin. The (Fig. the dentinal tubules ramify into openings of the dentinal tubules. monkeys. p. the tubules have a gentle S mation of peritubular dentin. cats. By preferentially remov- that mammalian orthodentin has evolved amaz. thus rats. Fig. 1. peritubular dentin is more quickly different at various distances from the pulp. As they approach The matrix of peritubular dentin differs from that the pulp. fated proteoglycans. process are synthesized by the odontoblast. whereas that between or DCJ to the pulp. acid etching agents used ingly constantly [33].8). thus making the one or more terminal branches. matrix that is deposited around each odontoblast tion of peritubular dentin. figure 2) around the odontoblast processes and thus trans. and released by reverse pinocytosis. the differentiating odontoblasts extended sev. of intertubular dentin in having relatively fewer face of the pulp chamber has a much smaller area collagen fibrils and a higher proportion of sul- than the surface of dentin along the DEJ. ing reduction in the diameter of the process.6) [32]. a ing the difference in size and number of tubules on the occlusal surface of coronal dentin (A and B) and at the cervical region of the root surface (C). Because of its lower content The number and diameter of the tubules are of collagen. and humans. toward the enamel.7). located between the rings of peritubular dentin as the odontoblasts withdrew. converged into one major process (Fig. the mean number and diameter of tubules Peritubular dentin is more highly mineralized decrease following the increased distance and therefore harder than intertubular dentin. there is a correspond- shape as they extend from the DEJ to the pulp. toward the center of the pulp. Investigators found the number hardness of peritubular dentin may provide added and diameter of dentinal tubules to be similar in structural support for the intertubular dentin. This combina- tion is responsible for the b exponential increase in c dentin permeability with depth (From Pashley [32]. The S-shaped curvature is presumably the result Peritubular dentin represents a specialized of the crowding of odontoblasts as they migrate form of orthodentin not common to all mammals. They are slightly tapered in the tubules is known as intertubular dentin the wider portion situated toward the pulp. ing peritubular dentin. 106. 1. trans- tinuous decrease in the diameter of the tubules ported in secretory vesicles out into the process. during dental restorative procedures enlarge the Near the DEJ. Presumably precursors of the dentin tapering is the result of the progressive forma. Liwei et al. With the for- In coronal dentin.10 Z. and dissolved in acid than is intertubular dentin. this is due to the dentin more permeable. but. indicating strengthening the tooth.6 Diagram illustrat.

(C) dentinal tubule A B C fibrils having diameters of 500–1000 Å.7 Diagrammatic representation of the differentiated odontoblast Odontoblast process Rough endoplasmic reticulum Golgi complex Mitochondria Cytoplasm Cytomembrane Nucleus Nucleolus Nerves Capillary Fibre Fig.1 Tooth Development: Embryology of the Craniofacial Tissues 11 Fig. (B) intertubular dentin.8 The cross section of dentinal tubules. 1. (A) Peritubular dentin. 1. These Interglobular Dentin The term interglobular fibrils are oriented approximately at right angles dentin refers to organic matrix that remains to the dentinal tubules. unmineralized because the mineralizing globules .

and lecular constituents include type I and type II radioactive have shown that sclerosis results in trimer collagens. Liwei et al.2 Types of Dentin most numerous near the basal lamina. Spaces between the predentin matrix. decreased permeability of dentin. One form of dentinal sclerosis is thought to Gla-proteins. situated immediately subjacent to the enamel or Apparently matrix vesicles are involved only cementum. These fibrils are closely packed becomes sclerotic. chondroitin-6-sulfate). As the globules expand. As the fan-shaped collagen fibers deposited immedi. process of mineralization progresses. Partial or complete obturation of dentinal tubules stitutes the major part of developmental dentin.. keratan sulfate.1. vitamin D-resistant rickets and vesicles within the predentin [35]. dentin phosphoproteins (DPP). Presumably hypophosphatasia). they fuse with adjacent globules until the matrix Mantle dentin is the first formed dentin and is is completely mineralized.12 Z.3. Its macromo. Dentinal front. This occurs most often in the 1.3 Mineralization of Dentin circumpulpal dentin just below the mantle dentin Mineralization of dentin matrix commences with where the pattern of mineralization is more likely the initial increment of mantle dentin. approximately 500 Å in diameter that surface or dental caries [36]. By limiting the sist of several proteoglycans (dermatan sulfate. and noncollagen elements con. glycosaminoglycans (GAGs). The crystals thus after the root is fully developed is referred to as released mix with crystals from adjoining vesi- the secondary dentin. they are 1. and in tooth development. This form appears to be a physiologic odontoblast cell lineage. the dentin dentinal tubules. solvents. estimated at 80–100 μm [34]. The apatite Developmental dentin is that which forms during crystals grow rapidly within the vesicles. Although matrix vesicles are distributed throughout the predentin. hyaluronate. dentinal sclerosis helps to shield the pulp chondroitin-4-sulfate.g. It is typified by its content of the thick in mineralization of initial layer of dentin. In certain dental phosphate crystals begin to accumulate in matrix anomalies (e.1. response to stimuli such as attrition of the tooth gen fibrils. it odontoblast and transported to the mineralization develops as a function of age [36].1. fail to coalesce. Dentinal sclerosis is easily together and form an interwoven network. and in the apical third of the root. and represent an acceleration of peritubular dentin a tissue-specific molecule which is unique to the formation. are mineralized. glycoproteins. recognized in histologic ground sections because Predentin is the unmineralized organic matrix of its translucency. and it is thought to bind to calcium and tubules can also become blocked by the precipi- play a role in mineralization. tation of hydroxyapatite and whitlockite crystals . cesses of odontoblasts. from irritation. That formed physiologically time. Developmental dentin is cles to form advancing crystal fronts that merge classified as orthodentin. Calcium to be globular than appositional. ing front projects along the collagen fibrils of the tial stages of dentinogenesis. to form small globules.3. tin. large areas of interglobular these vesicles bud off from the cytoplasmic pro- dentin are a characteristic feature. the vesicles rupture. The to grow as mineralization progresses. resulting in width of mantle dentin in human teeth has been an increased mineral content of the dentin. the advanc- ately subjacent to the basal lamina during the ini. diffusion of noxious substances through the den- heparan sulfate. Studies using dyes. which is due to the homoge- of dentin situated between the layer of odonto. may occur as a result of aging or develop in The organic matrix is composed mainly of colla. DPP is produced by the process.3. Circumpulpal dentin is formed after the layer 1. Hydroxyapatite crystals appear fibers are occupied by smaller collagen fibrils on the surface and within the fibrils and continue lying more or less parallel with DEJ or DCJ. When tubules is oriented at right angles to the long axis of the become filled with mineral deposits. neity of the dentin since both matrix and tubules blasts and the mineralized dentin. tin found in the teeth of all dentate mammals. the tubular form of den.4 Dentinal Sclerosis of mantle dentin has been deposited. and it con.

This type occurs in the trans. as in lucent zone of carious dentin and in attrited den. The close relationship enamel and exposes the dentin to the oral envi. In contrast. ally observed in association with marked pulpal however. the repara- tin and has been termed “pathological sclerosis. dentin caused by mechanical trauma or disease. The degree of irregularity of irritation dentin. the extent of cellular injury.5 Dentin Repair On the other hand. no repair is as much a reality in the pulp as in other tubules are formed. the amount of repar. the formation of reparative dentin occurs at the pulpal surface of primary of secondary dentin at 1.. reparative dentin How well it serves this function depends on many is less tubular and the tubules tend to be more factors.” tive dentin formed may resemble primary dentin in terms of tubularity and degree of mineralization.1 Tooth Development: Embryology of the Craniofacial Tissues 13 within the tubules. when a carious lesion has invaded den. the pulp retains its ability to form amount of primary dentin that is destroyed. This enables the vital pulp the formation of reparative dentin allows the pulp to partially compensate for the loss of enamel or to retreat behind a barrier of mineralized tissue. the case of a superficial carious lesion. but the potential for regeneration and irregular with larger lumina. the mature pulp bears a strong resemblance to .3. response to injury and appears to be a component The poorest quality of reparative dentin is usu- of the reparative process. the odonto- communicate with the carious lesion. Following tooth tion of the tooth surface is proportional to the development. In histologic sections. As the still unclear. blasts. Similarly. able. reparative dentin deposited in Dentin that is produced in response to the injury response to a deep carious lesion may be relatively of primary odontoblasts has been known by sev. The primary role of the pulp is to tubules of the primary or secondary dentin which produce dentin. Even which it resembles primary dentin) is quite vari.2 Pulp sites corresponding to areas of irritation. For example. The pulp is a soft tissue of mesenchymal origin tin. the extent to characteristic deserves serious consideration. irregularly formed dentin is reparative dentin. and reparative reparative dentin is probably determined by fac- dentin. In some cases.1. as the pulpodentin complex. The dental pulp is in many ways similar to blasts of the coronal pulp and are often cuboidal. The cells that form reparative connective tissues of the body. other connective tissues of the body. interglobular dentin. products of tis- It will be recalled that secondary dentin is sue degeneration further contribute to the inflam- deposited circumpulpally at a very slow rate matory stimuli assailing the pulp. dentin are not as columnar as the primary odonto. Compared to primary dentin. but its special The quality of reparative dentin (i. tertiary dentin. In fact. ered as a functional entity. It must be recognized. The reasons of within the dentinal matrix. Thus. If irritation to the pulp is relatively mild.3. dentin throughout life. that this type of dentin has also been inflammation. 1. the dentin may be so poorly observed in the pulps of normal unerupted teeth organized that areas of soft tissue are entrapped without any obvious injury [37]. arranged peripherally in direct contact when occlusal wear removes the overlying with dentin matrix. the pulp usually responds by depositing a residing within the pulp chamber and root canals layer of reparative dentin over the dentinal of the teeth. In general. throughout the life of the vital tooth.e. this phenomenon and the difference between the these areas of soft tissue entrapment impart a development and repair of irregular dentin are Swiss cheese appearance to the dentin. The term most commonly applied to tors such as the amount of inflammation present. sometimes referred to ative dentin formed in response to caries or attri. by specialized cells. reparative dentin is deposited over the reasons why dentin and pulp should be consid- exposed tubules. and the state of dif- presumably because it so frequently forms in ferentiation of the replacement odontoblasts. between odontoblasts and dentin is one of several ronment. tubular and poorly mineralized with many areas of eral different names: irregular secondary dentin. entrapped soft tissue degenerates.

help to explain why the electric pulp test tends to cally active odontoblasts. 1.2. the pulp lacks and hot drinks. antigen-presenting cells. and A-8 fiber terminals principally local in via the arterioles. yet. No true arteries or veins enter or ably sensitive to thermal stimuli such an ice cream leave the pulp. lymphatics. At this stage. and the stimula- the apical foramen or foramina in company with tion threshold of A fibers is relatively low con- nerve bundles. which in turn is cov- 1. the pulp. flow is of critical importance. Since the pulp is relative incompressible. The rela- extend into the odontoblast layer. The pulp houses a number of tissue elements. Certain peculiarities capillaries are surrounded by a basement mem- are imposed on the pulp by the rigid mineralized brane. embryonic connective tissue. A-8 and A-5 fibers. and give rise In the human premolar. the number of unmy- to a capillary network in the subodontoblastic elinated axons entering the tooth at the apex region. therefore careful regulation of blood but functionally these fibers are grouped together.14 Z. they fan out aching. Since with age there is a gradual reduc. which foramina and occasional arteriole through a lat. Being encased in a protective layer of dentin. Unlike most tissues. and these vessels pass through region of dentin–pulp junction. eruption [38].3. connective tis. This network provides the odontoblasts reached a maximum number shortly after tooth with a rich source of metabolites. conduction velocity. Moreover. blood flow in the region of the fewer than 100 myelinated axons were present. Approximately 90 % of the A fibers are A-8 Blood from the dental artery enters the tooth fibers. odontoblasts. the pulp is undeni- and venules. The innervation of the pulp a true collateral system and is dependent upon the includes both afferent neurons. it might be expected to be quite The pulp is actually a microcirculatory system unresponsive to stimulation. despite the low whose largest vascular components are arterioles thermal conductivity of dentin. throughout the pulp and feel the pain of burning. thus assuring tively late appearance of A fibers in the pulp may an adequate supply of nutrients for the metaboli. As the arteri.3. A-8 fibers may be slightly venules. ground substance. The pulp is a rather unique sensory organ capable odontoblasts. interstitial fluid. capillaries commonly more than 700 five years after eruption. and autonomic fibers. oles pass into the coronal pulp. including vascular tissues. Thus it is situated observed in capillary walls. myelinated A fibers and cannot be greatly increased. fenestrations (pores) are dentin in which it is enclosed. and occasionally. Liwei et al. ity. an average of 1800 Capillary blood flow in the coronal portion of unmyelinated axons and more than 400 myelin- the pulp is nearly twice that in the root portion ated axons were observed. fibroblasts.1 Vascular Tissues ered with enamel. Smaller vessels may enter the trast with C fibers which is probably distribute pulp via lateral or accessory canals. These fenestrations within a low-compliance environment that limits are thought to provide rapid transport of fluid and its ability to increase in volume during episodes of metabolites from the capillaries to the adjacent vasodilatation and increased vascular permeabil. Nerve fibers are usually classified according the vascular system of pulp decreases progres. and func- sively. tor to the central nervous system. diminish in size. . tion in the luminal diameters of these foramina. In more sensitive to stimulation than the A-5 fibers. fibers. The subodontoblastic be unreliable in young teeth. of transmitting information from its sensory recep- and other minor cellular components. provide neurogenic modulation of the microcircu- eral canal. and extravascular tissue. to their diameter. lation and perhaps regulate dentinogenesis.2. The A fibers include both volume changes can occur between arterioles. tion. toward the dentin.2 Nerve Fibers sues. although in some teeth. nerves. although reciprocal unmyelinated C fibers. which conduct relatively few arterioles entering through the root sensory impulses. [13]. In young teeth. pulp horns is greater than in other areas of the The number of A fibers gradually increased to pulp. In the pulp. there are two main types of sen- the total volume of blood within the pulp chamber sory nerve fibers.

9) and VII collagens are components of basement [39]. Type I is found in the skin. they are glycosylated and packaged in secretory Interestingly. cell-free zones. interstitial tissues. and lysine residues of the polypeptide chains are tain neuropeptides such as neuropeptide Y. 1. antigen-antibody as the telopeptide of the procollagen molecule. thus releasing the resistant to autolysis than other tissue elements. unlike collagen. The release of these pep. tyrosine hydroxy. rior alveolar nerve. procollagen. This may offer an explana- tion as to why instrumentation of the root canals of apparently nonvital teeth sometimes elicits a moderate level of pain. branch into smaller bundles. and substance P. or antidromic stimulation of the infe. V. Type V collagen is a constituent of occur until the final stages of root formation. ten- radicular pulp together with blood vessels. This is apparently due plasma membrane and secreted via exocytosis to the fact that nerve bundles in general are more into the extracellular matrix. fibers leading to the pulp results in depressed In collagen synthesis. Type III is found in most unmineralized the cell-rich zone. Once don. and dentin at top ferent combinations and linkages of chains mak- of the picture (From Avery [39]. they fan out beneath tilage. 208. dentin. product of this assembly is termed procollagen. and VII. 1. Type I collagen is synthesized One study showed that a reduction in pulpal by odontoblasts and osteoblasts. III.2. and the tropo- be able to respond to stimulation. consists of three polypeptide chains. vasoactive chains are assembled into a triple-helix configu- intestinal polypeptide (VIP). 1. Fig. bone. calci. reactions. and fibroblasts blood flow induced by stimulation of sympathetic synthesize types I. Full development of this plexus does not membranes. and pulp. figure 8) ing up the tropocollagen molecule have allowed collagen fibers and fibrils to be classified into a The nerve bundles pass upward through the number of types. tides can be trigged by such things as tissue and it has a terminal unit of amino acids known injury. Elastin fibers are confined to the walls of the arterioles and.3. and the tonin gene-related peptide (CGRP). A single collagen molecule. referred to as tro- pocollagen. C fibers might still cleaved by a hydrolytic enzyme. When these molecules reach the Golgi complex. for C fibers are better able to function in the presence of hypoxia. Furthermore. Type II occurs in car- they reach the coronal pulp. are not a part of the ECM. complement activation. Type IV axons known as the plexus of Raschkow (Fig. the protein portion of excitability of pulpal A fibers. The excitability of the molecule is formed by the polyribosomes of C fibers is less affected than that of A fibers by a the RER of connective tissue cells. it collagen molecules begin aggregating to form may be that C fibers remain excitable even after collagen fibrils. ration in the smooth endoplasmic reticulum. pulpal nerve fibers are relatively vesicles.9 Light microscopy showing the relationship of designated as either a-1 or a-2 depending on their parietal layer of nerves (plexus of Raschkow) below to the amino acid composition and sequence. odontoblasts.1 Tooth Development: Embryology of the Craniofacial Tissues 15 pulp. The proline reduction in blood flow. The vesicles are transported to the resistant to pulp necrosis. connective tissues.3 Connective Tissue Fibers Two types of structural proteins are found in the pulp: collagen and elastin. Pulpal nerve fibers con. Here the terminal telopeptide is Even in degenerating pulps. p. hydroxylated in the cisternae of the RER. and it is a fetal form found in and finally ramify into a plexus of single-nerve the dental papilla and the mature pulp. The lase. It is believed that aggregation of blood flow has been compromised in the diseased tropocollagen is somehow mediated by the . The dif- cell-rich.

2. some studies utilizing light and electron micros- copy have described lymphatic capillaries in 1. to reticular fibers in other high concentration of lysosomal enzymes. and differentiation of cells. loose connective tissues in that they are not Proteolytic enzymes. regarding it as the material into which defect.6 Accessory Canals ground substance. The conversion of soluble collagen into Laminin. Except for heparan sulfate and heparin. a break develops in the continuity of the sheath. on through the predentin into the dentin. growth. motility. They are very certain inflammatory lesions in which there is a similar.3.3. along the root. binds to type IV collagen and cell of tropocollagen molecules. organisms or their metabolic products to gain ence of GAG chains and a protein core to which access to the pulp.16 Z. hyaluronidases. tissue fibers also synthesize the major constitu. an important component of basement insoluble fibers occurs as a result of cross-linking membranes. the dental pulp has been reported in fully erupted The pathways of inflammation and infection are teeth [40]. both embedded in the pervading 1. thus creating a periodontal–end- tive tissues. When this occurs. tinogenesis does not take place opposite to the stance. forms an integrated predentin.2. Cells that produce connective Occasionally during formation of the root sheath.4 Ground Substance human and in cat dental pulps. glycoproteins.5 Lymphatics chrome stain or Mallory’s triple connective tissue The existence of lymphatics in the pulp has been stain. These molecules support cells. Proteoglycans are an important subclass of tissues lose their integrity. and mediate a variety of expose an accessory canal and thus allow micro- cell interactions. Connective tissue is a system consisting of cells and fibers. droitin sulfatases of lysosomal and bacterial ori- works.3. if not identical. Consequently. cells of the healthy pulp is the odontoblast layer. Fibronectin is a major surface glycoprotein This layer is located immediately subjacent to the that. Because of its content of between the dental sac and the pulp. The high. guish between venules and lymphatics by ordi- est concentration of these larger fiber bundles is nary light microscopic techniques. Liwei et al. surface receptors.3. Large collagen fiber bundles are not ground substance components. the ECM is respon. together with collagen. the chains are linked. den- matrix ECM is used to describe ground sub. The primary function of GAG chains is to act as adhesive molecules that can bond to cell Odontoblast Layer The outermost stratum of surfaces and other matrix molecules. An acces- polyelectric polysaccharides. In periodontal disease. small collagen fibers stain adhesion glycoprotein. the odontoblast layer is actually . The result is a small “accessory” canal fibers are deposited. the chains are composed of disac. GAGs. the development of a periodontal pocket may provide tissue turgor. with the odontoblast processes passing fibrillary network that influences adhesion. argyrophilic but can be demonstrated with special histochemical methods such as the Masson tri. The presence of collagen fibers passing gin are examples of acid hydrolytic enzymes that from the dentin matrix between odontoblasts into can attract components of the ground substance.2. these fibers are often referred to as von influenced by the state of polymerization of the Korff fibers. They have in common the pres.7 Morphologic Zones of Pulp charides. Tenascin is another substrate In the young pulp. ents of ground substance. The term extracellular producing a small gap.2. since it is not easy to distin- radicular pulp than in the coronal pulp. 1. sory canal can become established anywhere sible for the water-holding properties of connec. 1. ble portal of entry into the pulp if the periodontal teins. These fibers are much more numerous in the a matter of debate. black with silver impregnation stains and are thus Degradation of ground substance can occur in referred to as argyrophilic fiber. although usually found in the radicular pulp near the apex. odontic pathway of communication and a possi- Nearly all proteins of the ECM are glycopro. and chon- arranged in bundles and tend to form delicate net.

this odontoblast layer in the coronal pulp. there is motility ability is probably the first step in the often a narrow zone approximately 40 μm in formation of a new odontoblast. the radicular pulp.10). Since irreversibly injured odontoblasts are replaced by cells that migrate from the cell-rich Cell-Poor Zone Immediately subjacent to the zone onto the inner surface of the dentin.10 Beside dentin (1) and predentin (2). It contains the larger blood vessels blasts. 1. nerve fibers. zone are fibroblasts or pulpal cells. Although Since there are fewer dentinal tubules per unit cell division within the cell-rich zone is a rare area in the root than in the crown of the tooth. tains more cells per unit area than in the radicular pulp. commenc- odontoblasts appear as a flattened cell layer. it coronal pulp are usually columnar (Fig. The connective tissue cells in this zone depends on the functional status of the pulp. there are tall columnar odontoblasts (3) of the coronal pulp. with the more central region in the pulp. has been suggested that the cell-rich zone forms those in the midportion of the radicular pulp are as a result of peripheral migration of cells popu- more cuboidal. capillaries. Whereas the odontoblasts of the mature On this evidence obtained in rat molar teeth. of the pulp. the cell- rich zone may include a variable number of mac- The odontoblast layer in the coronal pulp con- rophages and lymphocytes.3.1 Odontoblast subodontoblastic area is a stratum containing a Because it is responsible for dentinogenesis both relatively high proportion of fibroblasts compared during tooth development and in the mature . The presence or absence of the cell-poor and nerves. width that is relatively free of cells. 1. Near the apical foramen.3.3. It may not be apparent in young pulps where den- tin forms rapidly or in older pulps where repara- tive dentin is being produced. the lating the central regions of the pulp. unmyelinated nerve fibers. and den. Note the presence of the cell-rich zone (5) and cell-poor zone (4) composed of the cell bodies of the odontoblasts. much more prominent in the coronal pulp than in dritic cells may be found among the odontoblasts. It is Additionally. sis. the occurrence in normal pulps. ing at about the time of tooth eruption. 1. Pulp Proper The pulp proper is the central mass and the slender cytoplasmic processes of fibro.3 Cells in the Dental Pulp Cell-Rich Zone Usually conspicuous in the 1. It is traversed by blood capillaries.1 Tooth Development: Embryology of the Craniofacial Tissues 17 Fig. death of odonto- odontoblast cell bodies are less crowded and are blasts causes a great increase in the rate of mito- able to spread out laterally. Besides fibroblasts.

The preameloblasts differentiate at a pulp. membrane of the odontoblast process closely Dentinogenesis first occurs in the developing approximates the wall of the dentinal tubule. the lamina becomes discontinuous iting membrane. With the onset of dentinogenesis. Differentiation of epithelial and mesenchymal the dental papilla becomes the dental pulp. into short columnar cells with basally situated theories as to their functional significance sug- nuclei (Fig. Liwei et al. Several cytoplasmic projections gest that they may be involved in cytoplasmic from each of these cells extend toward the basal extension. the odonto- tively. These cells stop dividing and elongate rigidity. With the tural components of the odontoblast process and onset of differentiation a single layer of cells. or simply the lamina. and matura. mature ameloblasts appear a process from each odontoblast becomes accen- before the odontoblasts have fully matured. although small amounts of type V the enamel).18 Z. rial. tubule wall and the process. and their presence within the tubules an important role in the initiation of makes dentin a living tissue [41]. The peritubular dentin matrix lining the more collagen fibrils accumulate subject to the tubule is circumscribed by an electron-dense lim- basal lamina. Although their precise role is unknown. the its lateral branches. These vesicles subsequently play tubules. mineralization. These straight themselves along the basement membrane sepa. During dentino.7). it apparently cannot undergo further cell division. depositing matrix at a rate of approximately faster rate than the corresponding odontoblasts so 4–8 μm per day in their wake. Concurrently the odontoblasts extend several If this is indeed the case. In addition . Such spaces may nar cells. Membrane-bound vesicles bud off collagen have been found in the ECM. occurs during the bell stage of tooth devel. blast process. ameloblasts undergo differentiation. tooth. cells into ameloblasts and odontoblasts. interspersed among the collagen fibers of the genesis. It is in this region that odonto. the dental papilla consists of the formation of peritubular dentin. structures follow a course that is parallel with the rating the inner enamel epithelium from the dental long axis of the cell and impart the impression of papilla. The production of the first dentin matrix contain collagen fibrils and fine granular mate- involves the formation. the preodontoblasts are still provision of a structural framework. respec. the spaces between the ameloblast processes. At this stage. ally produce relatively large spaces between the blasts reach full maturity and become tall colum. Before differentiation of space within the tubule and somehow mediates odontoblasts. 1. den. As the dentinal tubules are formed. Within this matrix. the odontoblast is the most characteristic from the odontoblast processes and become cell of the pulpodentin complex. organization. of ameloblasts. In tuated and remains to form the primary odonto- spite of this difference in rate of maturation. changes are Dentinal tubule forms around each of the happening across the basement membrane in the major odontoblastic processes which occupy adjacent dental papilla. and eventually disappears. the odontoblasts form the dentinal dentin matrix. transport of materials. As stance. The odontoblast is considered to be fixed post- lagen fibers become organized and extend into mitotic cell in that once it has fully differentiated. It is around these processes that the tin matrix is formed before enamel matrix. blasts commence to move away toward the central opment [42]. Microtubules extend from presumptive odontoblasts (preodontoblasts) align the cell body out into the process. which presumably represents ground sub- tion of collagen fibrils and proteoglycans. resulting in the formation of Apparently the odontoblast synthesizes mainly enamel spindles (dentinal tubules that extend into type I collagen. that at any given level. tooth at sites where the cusp tips or incisal edge Localized constrictions in the process occasion- will be formed. the life-span of the small processes toward the ameloblasts. Some of odontoblast coincides with the life-span of the these become interposed between the processes viable pulp. As predentin matrix is formed. This occurs as the col. The plasma relatively undifferentiated. Microtubules sparsely distributed polymorphic mesenchymal and microfilaments are the principal ultrastruc- cells with wide intercellular spaces.

like macrophages. number as the pulp ages.2 Pulp Fibroblast of replacement odontoblasts appears to occur pri- The most numerous cells of the pulp tissues marily among fibroblasts. are usually found in close proximity to blood ves- fibroblasts are particularly abundant in the cell. As they mature. When activated by the and fibers.4 Dendritic Cell remain in a relatively undifferentiated modality as Dendritic cells. growth factors. a phosphoprotein involved observation of large numbers of reticulin-like in extracellular mineralization.3. they are able to act as scaven- evenly distributed within the ground substance.1 Tooth Development: Embryology of the Craniofacial Tissues 19 to proteoglycans and collagen. that because of distinct histochemical differences. where it can interact with specific cells. Because of their mobility and polygonal and appear to be widely separated and phagocytic activity. Thus. enchymal cell lines. given the proper signal.3 Macrophage well as proteoglycans and GAGs. In the linked to mineralization but whose precise role is young pulp. dead Cell-to-cell contacts are established between the cells. for these cells do seem to 1. removing extravasated red blood cells. gap junctions. are not present in the pulp. collagen fibrils commence to appear. exposure or pulpotomy. are sparse. Phosphophoryn is fibers in the pulp. tion as odontoblasts. they are also responsible for that have left the bloodstream. the odontoblast tissues. pulpal fibroblasts can be regarded as odontopro- ing rise to cells that are committed to differentia. secretory to lymphocytes. appropriate inflammatory stimuli. and differentiated into macrophages. particu- shorter. This perception has been fortified by the secretes phosphophoryn. larly dentinal bridge formation following pulp pletion of root development. There may be an element of truth in this statement. entered the tis- collagen turnover in the pulp. it appears that appear to be tissue-specific cells capable of giv. ing or injured odontoblast has a decreased num. and foreign bodies from the tissue ingested multiple processes that extend out from each of material destroyed by the action of lysosomal the cells. Many experimental models have been devel- ber of organelles and may become progressively oped to study wound healing in the pulp. nerves. gers.3. One study demonstrated that mitotic activity preceding the differentiation 1. they never grow up. sels. The odontoblast also secretes reticulin fibers. there is a relative decrease in the num.3. With an Such interaction is obligatory for the induction of increase in the number of blood vessels. the RER proliferates. genitor cells. and other cytokines. The processed antigen is bound vesicles appear. macrophages ber of fibroblasts in the pulp. reactions by processing antigen and presenting it plex enlarges. are capable of producing a large variety of solu- A colleague once remarked that the fibroblasts ble factors including interleukin-1. a proportion of macrophages. cell-mediated immunity. These changes can begin with the com. However. Along the outer surface of the cell body. which provide for electronic cou.3. These cells synthesize type I and III collagen as 1. the when primed by cytokines. participate in immune cells become stellate in form and the Golgi com. but they progressively increase in In contrast to the active odontoblast. and the fibroblasts take on the to class II histocompatibility antigens on the characteristic appearance of protein-secreting macrophage. tumor necro- of the pulp are very much like Peter Pan in that sis factor. an enzyme that is closely phoid organ. Similar cells are found in the . it has been concluded unique to dentin and is not found in any other mes. the rest. These cells are quite active in endocytosis rich zone. They Although distributed throughout the pulp. receptors present on immunocompetent T cells. the nonargyrophilic collagen fibers yet to be illuminated. sues. such as most of gingiva and lym- alkaline phosphatase. The early differentiating fibroblasts are and phagocytosis. since they Tissue macrophage or histiocytes are monocytes degrade collagen. Many of these contacts take the form of enzymes.3. are cells of the compared to fibroblasts of most other connective immune system.3. pling of one cell to another. In addition.

Lymphocytes 1. the pulp new mesenchymal cells arise from cells The formation of a mesh-like structure in the other than pulpal fibroblasts.1 The Initiation of Tooth Root have also been observed in the pulps of impacted Development teeth. formation.20 Z. MSCs provide a renewable source of development together [43] progenitor cells to differentiate and replace those HERS is the morphogenesis signal of the ini- lost. Together with macrophages and lymphocytes. Like macrophages. dendritic cells. HERS. dendritic cells are believed to par. the pulp. But mast widely distributed in connective tissues. the epithelial root sheath is lized in response to tissue damage. the epithelial root sheath enveloping Consequently.4 Root Development weakly phagocytic. subject of considerable attention because of its ily found in lymphoid tissues. well-differentiated fibro. normal pulps from the human teeth. the well equipped with cells required for the initia. These dental follicle cells 1. Similarly. In addition. The interaction between dental epithelial 1. but they are also dramatic role in inflammatory reactive. located between the two regions of neural crest- some authors hold the opinion that primordial derived mesenchyme: the dental papilla and the mesenchymal cells persist in adult pulp tissues as dental follicle. MSCs are found in tiation of tooth root development [44]. and T lymphocytes indicates that the pulp is After the crown formation is nearly complete. including cells also present in the normal pulp tissue. However. tum.3. Dendritic cells are primar. This cell has been the called Langerhans cells. After root dentin blasts are derived from mature fibroblasts. newly formed root dentin surface through the epithelial root sheath.6 Mesenchymal Cell ring of the crown and grows in the apical direc- Mesenchymal stem cells (MSCs) are found in tion. termed Hertwig’s epithelial root sheath many adult tissues and organs. dental papilla cells. following the bell stage. where they are relation to blood vessels. tooth root begins to develop. the special tion of immune responses. dendritic cells phago- cytose and process antigens but are otherwise only 1. Then. processes and the presence of cell surface class II antigens.5 Lymphocyte and neural crest-derived mesenchymal cells is T lymphocytes and B lymphocytes were found in essential for tooth development.3. thelial layer of the HERS and the epithelial base- blasts undergo rapid serial division to give rise to ment membrane induced to become odontoblasts new fibroblasts.3. In tissues that (HERS). bilayered epithelial sheath is formed from the outer and inner enamel epithelium at the neck 1. replacement odonto. small numbers and remain quiescent until mobi. In pulp tissue.7 Mast Cell differentiate into cementoblasts to form cemen- Mast cells are widely distributed in the connec. Liwei et al. where they occur in small groups in epithelial–mesenchymal transition to become . Root development is one of the important stages ticipate in immunosurveillance in the pulp. in tooth development process. Morphologically. there is no need to postulate that in the root begins to be interrupted or perforated. the dental papilla cells adjacent to the inner epi- during wound healing. T8 (suppres- sor) lymphocytes were the predominant T lym- phocyte subset present in pulps. In the majority of tissues. epidermis and mucous membranes. When the HERS grows apically. This controversy is HERS allows dental follicle cells to contact the still unclear and needs more researches. some of the HERS cells undergo tive tissues. These cells are termed antigen-presenting although they are routinely found in chronically cells and are characterized by dendritic cytoplasmic inflamed pulps. and later to form root dentin. The presence of macrophages. “undifferentiated” mesenchymal cells. and dental grow continuously or exhibit high rates of cell follicle cells form the organ primordium of tooth turnover.

Deletion of Smad4 ABCG2.1 Epithelial Cell Rests tum development and may differentiate into of Malassez (ERM) cementocytes. p75. ecto- 1. Primary HERS/ERM cells had typical epithe. remained unknown. Epithelial cell rests of Malassez (ERM) are involved in the maintenance and homeostasis of the periodontal ligament. the expression of embryonic stem cell Ablation of Smad4 in the dental mesenchyme markers such as Oct-4. but the fate of HERS has epithelial–mesenchymal interactions. such as to prevent root resorp. Moreover. collagen fibers secreted by dental fol. HERS cells also participate in the cemen- 1. ΔNp63. Moreover. and SSEA-4 was (Osr2-IresCre:Smad4fl/fl mice) results in short detected [46] root formation and defects in odontoblast differ- entiation and dentin formation. They Smad4 is a central mediator of the canonical expressed epithelial stem cell-related genes: TGF-β signaling pathway. 1. At least 6 possible the root throughout root formation and do not outcomes of HERS have been proposed: (1) epi.1 TGF-β/BMP Signaling and differentiate into the lining epithelium of The TGF-β superfamily of cytokines is composed periapical cysts. At the come in contact with the outer dentin surface. Loss of Smad4 results in the upregulation of two dental ectomesenchymal tissues: dental of canonical Wnt signaling and downregulation papilla and dental follicle [47]. and others separate incorporation into the advancing cementum front. (PDLSCs) and forming cementum in vivo [48]. which are Wnt pathway epithelial rests and cords. (2) apoptosis. activins. allowing other cells to inhibitors. is a structural boundary mice. BMPs. and regeneration [49]. induce cementum formation.4. erupts into the oral cavity to establish occlusal HERS cells may be involved in regulating dif- contacts with the opposing teeth and performs its ferentiation of periodontal ligament stem cells physiological function. results in the blockage of TGF-β/BMP signaling.2.1.4. maintained for more than five passages. ERM can be stimulated to proliferate in cial role in the process of root development. several genes were found to play cru- hand. cle cells penetrate the HERS network to contact dentin. response to injury in rats.2 Related Signaling Pathway ber of functions. It breaks up into of Dkk1 and Sfrp1. On the other Recently.1 Tooth Development: Embryology of the Craniofacial Tissues 21 cementoblasts and form cementum [13]. and onto the surface of the dentin before dental folli- (6) differentiation into cementoblasts [10]. of TGF-β. Until now. ERM can proliferate 1.2 Induction of Differentiation pic bone-like structures replaced normal dentin of Mesenchymal Stem Cells in the teeth of Osr2-IresCre:Smad4fl/fl mutant HERS. same time.4. and related proteins. disappear. Nanog. of Root Morphogenesis tion. and Bmi-1. and maintain the homeostasis of the PDL [45]. (3) the surface of the cementum. (5) cells secrete extracellular matrix components migration toward the periodontal ligament. The ERM have a num. Previous studies have shown that Hertwig’s Dental follicle cell sheets induced by HERS cells epithelial root sheath plays an important role in are able to produce periodontal tissues through root development. HERS (4) epithelial–mesenchymal transformation. When stimulated by inflammatory cytokines. and they opmental biology.4.1. Most of the HERS cells are attached to thelial cell rests of Malassez. This sandwich structure plays at least two impor- licle cells are embedded into the new cementum tant roles during root formation: biomineraliza- matrix and fix the root in the jaw bone. the fate of HERS HERS cells are detectable on the surface of and its function are not clear. to become the epithelial rest of Malassez. Following tion (cementogenesis and dentin formation) and tooth root development and elongation. TGF-β signaling plays an important role in devel- lial cell morphology and characteristics. . disease. morphologically. EpCAM. the tooth induction of root organization.

Wnt10a is expressed in 1. 1.2. Moreover. fate decisions of stem cells in multiple tissues.2 SHH Signaling At embryonic day 19. has been shown to be strongly expressed in ing Tgfbr2 [50].4 Notch Signaling development is retarded [52]. and root 1.4. The canonical Wnt signaling cal loop stem cell niches. ing crown formation. β-catenin stabilization in the dental mesenchyme Odontoblast differentiation is delayed and Dspp can lead to excessive dentin formation. dental mesenchyme differentiation is Lef-1 overexpression accelerates odontoblast dif- arrested at the late bell stage and secretory stage. odontoblast-lineage cells and is required for root Bone morphogenetic protein 4 (BMP4) is formation. and Axin2 is also expressed in developing odontoblasts and dental Tooth eruption is the movement of the tooth from pulp cells. and some novel genes were found 1. Gli1. Comparing different animal models provides signaling. In K14-Noggin transgenic mice. Studies assessed the localiza. ferentiation of dental pulp cells and constitutive with no detectable expression of Dspp.3 Wnt Signaling differentially expressed. Liwei et al. Sel1l. is strongly expressed in pre- more detail about TGF-β signaling during root odontoblasts but is decreased in secretory odon- dentin formation. Edar. root development. cells in the continuously growing mouse incisors. sor of rat began differentially developing: the is expressed in the dental epithelium and plays an molar formed double-layered cells of the root essential role during tooth development. During dentin formation. It is well known the incisors. the molar and the inci- Shh. Tissue-specific inactivation of secreted by mesenchymal cells. that Wnt/β-catenin signaling plays multiple roles in various stages of tooth morphogenesis [54]. it was recently reported that mice. hence the hypothesis that mesen. BMP4 receptor (BMPR-1B). Shh is strongly expressed in By using the subtractive hybridization method.4. The Notch role in morphogenesis and cellular differentiation signaling contributes to the maintenance of cervi- in many tissues.4. Dkk1. β-catenin expression is eventually detectable in mice lack. which suggests a function in root for. [51]. Nfic. a transcript activated by Shh. molars lacking roots and aberrantly thin incisors. a member of the hedgehog signaling family. SEL1L. molar epithe- lial root sheath cell proliferation is abated. which activates the expressed in the molars but weakly expressed in expression of Wnt target genes. During sheath while the incisor formed a cervical loop. These reports strongly suggest that modulation of tions of BMP4. an inhibitor of Wnt the original developmental site to the functional .22 Z.2. The Notch pathway regulates the renewal and In the early development of mouse molar root. In Osr2-IresCre:Smad4fl/fl toblasts. is also incisor tissues was successfully constructed. GATA6. chymal STRO-1-positive cells are epithelial root Notch signaling is required for epithelial stem sheath BMP signaling pathways of target cells. mesenchymal progenitor cell markers such as Notch1 and Notch2 as well as the Notch target STRO-1 with BMP receptors are expressed in the gene Hes1 are expressed in the putative stem dental follicle. cell survival and enamel formation in the contin- uously growing mouse incisor [55].2. ated by dot blot and sequencing. In addition. which were strongly The Wnt family of proteins plays an important related to the tooth root patterning. and Wnt/β-catenin signaling may play an important BMPR-2 during molar root formation in mouse role in odontoblast differentiation. a the HERS. was strongly accumulation of β-catenin. the negative pathway involves the stabilization and nuclear regulating factor of notch signaling. subtraction cDNA library of the rat molar and mation.4. acting on the dental β-catenin in developing odontoblasts produced epithelium as a regulator of cell differentiation dur.3 Tooth Eruption odontoblast-lineage cells. detectable in the root epithelium (HERS) and Differentially expressed gene clones were evalu- mesenchyme [53].

Yamamoto H. such as RANKL. development.12:575–87.2010. Ge J. resorbed on the coronal side. as canine atrium. Meanwhile. Nanotechnology for regenerative medicine. considered as the main force responsible for the 13. nnano. Fate of These studies provided convincing evidence that HERS during tooth root development. Circulation. Recently. Oral Dis. 1990. Dev Biol. structure of human enamel. acceptable theories is that asymmetric bone Baltimore: Lippincott Williams & Wilkins. When bone Sciences. One of the most 1. microscale. New observations of the hierarchical removed and replace with another artificial tooth. eruption. preocclusal eruption. 1989. However. Anat Rec. surrounding the enamel organ of each tooth. Oral development and plays a critical role in regulating osteoclasts and histology. Deutsch D. some important signaling molecules 9. Kokubyo Gakkai Zasshi. root formation is not required for tooth eruption. Nanomaterials in preventive Furthermore. periodontal liga. J Dent Res. 2003. 7. and also challenged the previously supposed 11. Frame LH. 1989. Langman’s medical embryology. monkeys. and the void created by and its surrounding tissues and is temporally and the absence of roots during eruption was filled spatially controlled to coordinate the growth of with the alveolar bone. 2010. Hayashi T. Chun YW. It is a continuous process. tooth eruption. 3rd ed. 2003. doi:10. In some patients be divided into 5 stages. J Tissue Eng Regen Med. doi:10. including human.9:19–23. it was 5.5:565–9. from nanoscale to which the dental follicle was kept intact in situ. Steele PF. 2007. Pareta R. which is a loose connective tissue sac and craniofacial evolution. bone formed on the 3. if the tooth germ was 6. 12th ed. It is thought that the den.79:406–16. 10.1007/ cle from developing premolars of dogs prevented s10544-008-9264-6. Huang X. doi:10.83 [pii]. Chai Y. the mouth. respectively for pre. Webster firstly shown that the removal of the dental folli. Developmental properties of the tooth eruption. Sadler TW. 2012. Boyden PA.21.334:22–30. BMP2. Crawford PJ. ments. removal of either the coronal or dentistry. organ and dental papilla by renal transplantation: For a long time.57:652–66.1038/nnano. New York: Thieme. Hoffman BF. St. 2010.1002/term. basal halves of the dental follicle also prevented doi:10. the specific cellular. Origins and basal side of the tooth. Amelogenesis were identified at both these processes for tooth imperfecta: a classification and catalogue for the 21st century. and function. Khang D. In 1980s. plasticity of neural crest cells and their roles in jaw tal follicle. . root development has been effects of discrepancy in number of these two compo- nents. Nat Nanotechnol. structure. tooth eruption. and roots in the process of tooth 12.2010. Carpenter J. which may affect root eruptive movement.83. Ten Cate’s oral histology: development. et al. and so on. and into the mouth. TJ. termination. intraosseous eruption. molecular. Avery N. and genetic mechanisms governing tooth eruption remain unclear. Bringas Jr P. with special diseases. Hannig C. found that rootless tooth can still erupt into the 2004. remodeling around the tooth is responsible for 2. Int J Dev Biol. and rodents. Recombinant study of mouse enamel eruption. References Until now.1:185–91. Cui FZ. Nanci A. Slavkin HC. 2014. All of these indicated that the jaw and the position of other teeth. Trainor PA. 47:541–53. Aldred MJ. Savarirayan R. more and more studies Hertwig’s epithelial root sheath in mice.83:688–92. which can dogs.1002/ requirement of dental pulp. Louis: Elsevier Health the teeth moving into the oral cavity. 4. Each step involves the removal of roots in dogs can erupt into oral intense reciprocal interactions between the tooth cavity at normal speed.1 Tooth Development: Embryology of the Craniofacial Tissues 23 position through the alveolar bone and gingiva in oral cavity in many species. Hannig M. Avery JK. the dental follicle is essential for tooth eruption 2009. Biomed Microdevices. Structure and function of enamel gene products. Melton KR. Observations during entrainment and well as the basal part causing bone formation. the rootless tooth crown did erupt mucosal penetration.1092240209. Developing premolar teeth with post-occlusal eruption. there are several theories explain- ing how the tooth erupts [56]. osteoblasts during this process. ar. Activation map- ping of reentry around an anatomic barrier in the bone resorption and the eruption pathway. the artificial tooth still erupted on schedule.224:189–210. Manzanares M. with the coronal part controlling 8. 2002. However.

et al. Lesot H.1002/(SICI)1097-0282(19981005)46:4<225::AID. Lv L. Anat Rec. Altered 35. Wright JT. 31. type in X-linked amelogenesis imperfecta. Copenhagen: Munksgaard. Amelotin – a novel secreted. Paine ML. The detection and prevalence of reactive and phys- M110473200. 30. Gibson CW. Abbott C. doi:10. syndrome. Johnsen D. et al. Tan J. gene expressed in rat ameloblasts codes for proteins 43. Enamel biology logodaedaly: getting to 45. 2009. Repair potential of the pulp. M104624200 [pii]. and expression in prokaryotic and 17. 36. ameloblast- Snead ML. 19. and aging. activity. J Dent Res.84:266–73. Amelogenin-deficient mice display 41. nocytochemistry of noncollagenous matrix proteins in The human enamel protein gene amelogenin is rat mandibles processed with microwave irradiation. Liwei et al. Yu X. Du C. 1989. 34. 1986. 1984. et al. Am J Hum Genet.1159/000091380. Dev Dyn. doi:0888-7543(89)90295-4 [pii]. effect of aging on tooth morphology: a study on 10.1074/jbc. Bartlett JD. Couve E. Dental follicle cells and cementoblasts with cell binding domains. Mohandas TK. mineral content in MMP-20 null mouse enamel is Oldak J. The 18. odontoblast activity. Fincham AG. J Oral Pathol Med. assessment of neural development in human premo- 32:119–24. CW. Arana-Chavez VE. J expressed from both the X and the Y chromosomes. cat. High-resolution immu- 15.110:358–65.46:225–38. glycosyl- 307/5714/1450 [pii]. Rymer H. ation. Beniash E. Mutations in CNNM4 cause Jalili diameter and number of dentinal tubules in rat. Zhang T. Zeichner-David M. Stanley H. doi:10. Li S.CO. ajhg. 1995. Decreased 16. Odontoblast differen- 25. et al. 40. 2004. Role of Hertwig’s epithelial Cells Tissues Organs. Mutation in kallikrein 4 causes autoso. effect through amelogenin molecular self-association. Lee DH. 28. Lei YP.12:257–89. Lau EC. 14. Rosenbloom SJ. Ryu O. Brannström M. doi:10. 2013. Quantitative amelogenin biochemistry. The amazing an amelogenesis imperfecta phenotype. Salido EC. The characteris- the root of the problem. 2002. Falini G. Matrix vesicles: their role in calcification. 29. Yu LC. 1–10. A novel tiation. Pereira J. 2003. J Bone Miner Res.2-R. consisting of autosomal-recessive dog and monkey: a comparative scanning electron cone-rod dystrophy and amelogenesis imperfecta. Res. Wurtz T. Iwasaki K.92:765–72.0.5650110705. 1998.61:54–60. 21. Weinreb M. 2002. J Med Genet. Science. 1992.01.CO. 91380 [pii]. S0002-9297(09)00016-0 [pii]. Eur J Oral Sci. reparative dentin and dead 20. 37.2-R [pii]. Histology of the human tooth. Int J Dev Biol.11:899–904. microscopic study. Begue-Kirn C.1105675. M. 2003. Fukumoto S. 1975.39:51–68. Human and mouse amelogenin gene loci specific protein. lars. Yuan ZA. 2014. Arch Oral Biol. root sheath cells in tooth root development.191:67–73.1074/jbc. et al.277:17112–6. Moradian-Oldak J.50:303–16. Snead ML.41:545–9. Genomics.205:421–9. Relationship of phenotype and geno.33:243–50. et al. Porcine kallikrein-4 activation. doi:10. Interodontoblastic 23. in human X-linked amelogenesis imperfecta (AIH1). Moradian-Oldak J. induce apoptosis of ameloblast-lineage and Hertwig’s 11:883–91. Connect 7:205–12.181:189–95. 33. Mjör IA.2009. Malhotra M. et al. Sauk JJ. Hammarstrom L. Recent advances in 38. Yamada Y. or “who’s on first…”. et al. doi:83/12/909 [pii]. collagen (von Korff fibers) and circumpulpal dentin mal recessive hypomaturation amelogenesis imper. ameloblast differentiation and enamel formation. Yen PH. Essential roles of ameloblastin in maintaining 2012. Moradian. 1996. Osorio R. The 0282(19981005)46:4<225::AID-BIP4>3. Koprivnikar K. Supramolecular assembly of amelogenin prominent during the maturation stage.83:909–13. Am J Anat.228:651–63.307:1450–4.5650110703. J Bone tics of epithelial cell rests of Malassez during tooth Miner Res. nanospheres into birefringent microribbons. doi:S0003996996000994 [pii]. fecta.49:1099–109.24 Z. 2001.84:1127–32. Connect Tissue Res. 1973. Nanci A. Hart PS.44 Suppl 1:72–8.45: jbmr. doi:10. . An amelogenin gene defect associated with human 32. Fincham AG. 1983.009. through the Fas-Fas ligand pathway. Gibson eukaryotic hosts. Pindborg JJ. Pashley D. X-linked amelogenesis imperfecta. Smith CE. Slavkin HC. 1981. Fermani S. Collier PM. 1996. Schultz J Biol Chem. Ruch J. J Dent Res. Parry DA. Forssell-Ahlberg K. Am J Hum Genet. Yoshida S. Broom C. Harshbarger J. doi:10.42:235–42. Eur J Oral Sci.1002/(SICI)1097. Nitzan DW.276:31871–5. iologic sclerotic dentin. doi:10. 24. 1996.1002/jbmr. Interaction of tracts beneath various types of dental lesions accord- amelogenin with hydroxyapatite crystals: an adherence ing to tooth surface and age. 44. amelogenin self-assembly based on mutations observed Dentin Dentinogen. 1995. 2005. are on the sex chromosomes. 22.1126/science. Dynamics of the pulpo-dentin complex. Shapiro LJ. Edwall L. 1991. J Endod. Histochem Cytochem. M110473200 [pii]. J Mol Histol. Yamada A. Slaby I. Oral Surg Oral Med Oral Pathol.120:29–37. epithelial root sheath/epithelial rests of Malassez cells 26. Avery J. Nonaka K. Schmachtenberg O.7(2):104–33. 39. Acta Odontol. J Dent 2001. 2004. Azaz B. Bishop M. Michaeli Y.1002/ eruption of development mice. 2005.1016/j. 162–8.1:135–54. Crit Rev Oral Biol Med. 1983. BIP4>3. autophagy. J Biol Chem. Spiegel E. doi:10. formation: an ultrathin serial section study in the cat. 27. 42. Cerny R. Snead ML. impacted teeth.0. 1997. Lee JH. Tissue Res. 2005. Shapiro LJ.4: doi:84/12/1127 [pii].M104624200. Wang Y. Bonucci E. Biopolymers. Dickerson K.

1 Tooth Development: Embryology of the Craniofacial Tissues 25

46. Nam H, et al. Expression profile of the stem cell sheath during tooth root development. Cell Tissue
markers in human Hertwig’s epithelial root sheath/ Res. 2008;333:503–9.
Epithelial rests of Malassez cells. Mol Cells. 2011;31: 52. Plikus M, et al. Morpho-regulation of ectodermal
355–60. organs: integument pathology and phenotypic varia-
47. Sohn WJ, et al. Contribution of mesenchymal prolif- tions in K14-Noggin engineered mice through modu-
eration in tooth root morphogenesis. J Dent Res. lation of bone morphogenic protein pathway. Am J
2014;93:78–83. Pathol. 2004;164:1099–114.
48. Xiong J, Gronthos S, Bartold PM. Role of the 53. Khan M, Seppala M, Zoupa M, Cobourne MT.
epithelial cell rests of Malassez in the development, Hedgehog pathway gene expression during early
maintenance and regeneration of periodontal development of the molar tooth root in the mouse.
ligament tissues. Periodontology. 2013;2000(63): Gene Expr Patterns. 2007;7:239–43.
217–33. 54. Chen J, Lan Y, Baek JA, Gao Y, Jiang R. Wnt/beta-
49. Yamashiro T, Tummers M, Thesleff I. Expression of catenin signaling plays an essential role in activation
bone morphogenetic proteins and Msx genes during of odontogenic mesenchyme during early tooth devel-
root formation. J Dent Res. 2003;82:172–6. opment. Dev Biol. 2009;334:174–85.
50. Oka S, et al. Cell autonomous requirement for TGF- 55. Felszeghy S, Suomalainen M, Thesleff I. Notch sig-
beta signaling during odontoblast differentiation and nalling is required for the survival of epithelial stem
dentin matrix formation. Mech Dev. 2007;124: cells in the continuously growing mouse incisor.
409–15. Differentiation. 2010;80:241–8.
51. Hosoya A, Kim JY, Cho SW, Jung HS. BMP4 signal- 56. Marks Jr SC, Schroeder HE. Tooth eruption: theories
ing regulates formation of Hertwig’s epithelial root and facts. Anat Rec. 1996;245:374–93.

Biofilm and Dental Caries
Xu Xin, Zhou Yuan, Shi Wenyuan, Liu Yaling, and
Zhou Xuedong

2.1 Dental Plaque and Microbial most microbes live and grow? From the colorful
Biofilm microbial mats in Yellowstone geothermal area to
the sophisticatedly structured microbial commu-
2.1.1 Bacterial Biofilm: nity on tooth surfaces, we have the answer.
An Advanced Mode of Life The Concept and Discovery
Bacteria grow in two different ways: planktonic of Biofilm
and biofilm forms. Decades ago, most microbiol- Biofilm is defined as aggregates of bacterial cells
ogists characterized and studied planktonic bacte- attached to a surface and embedded in a poly-
ria in liquid culture in which bacteria were floating meric matrix that is self-produced and helps the
free cells. In this period, plenty of fundamental community to gain tolerance against antimicrobi-
work in microbiology was accomplished [7]. als and host defenses. Usually biofilm cells are
However, it is estimated that only less than 0.1 % adhered to a surface, for example, catheter or
of the microbial consortia in natural environment tooth surfaces. With the extensive biofilm stud-
grow in planktonic state [40]. Then how do the ies, the surface attachment feature is not indis-
pensable for biofilm recognition now [15].
The first observation of bacteria on surfaces
was made by Antonie van Leeuwenhoek in 1684
[15]. He observed various types of the numerous
X. Xin • Z. Yuan • Z. Xuedong (*) “animalcules” in the tartar taken from his own
State Key Laboratory of Oral Diseases, teeth directly by microscope. He also found the
West China Hospital of Stomatology, preliminary evidence of antimicrobial tolerance
Sichuan University, No. 14, Section 3, of biofilm from the fact that the surface-attached
Renmin South Road, Chengdu 610041,
People’s Republic of China cells on his teeth could survive after rinsing with
e-mail: zhouxd@scu.edu.cn vinegar, while cells removed from teeth could
S. Wenyuan be killed by vinegar [146]. At that time, the
School of Dentistry, knowledge and techniques in microbiology
University of California-Los Angeles, were too limited to understand the little com-
Los Angeles, CA, USA munities on surfaces. Recently with molecular
L. Yaling and bioinformatics techniques, the characteriza-
Advanced Education in General Dentistry, tion of microbial growth and development in
Eastman Institute for Oral Health,
University of Rochester, Rochester, NY, complex communities on surfaces have been
USA highly promoted [82].

© Springer-Verlag Berlin Heidelberg 2016 27
Z. Xuedong (ed.), Dental Caries: Principles and Management, DOI 10.1007/978-3-662-47450-1_2

28 X. Xin et al. Extracellular Polymeric extracellular DNA (eDNA), and other substances
Substances of Biofilm from cell lysis. Therefore, within the matrix, gene
The structure of biofilm is highly varied depend- horizontal transfer through eDNA, mutualism or
ing on the growth environment and component antagonism interactions, and nutrient accumula-
cells. In addition to the bacterial aggregates, tion are active [62, 212]. By supporting vertical
another major component, the structural back- extension of biofilm, EPS also reduces the
bone of biofilm, is the extracellular matrix com- biomass density to buffer impact from external
posed of self-secreted extracellular polymer substances. Moreover, EPS can protect the
substances (EPS) [55]. EPS is a highly diverse microbial consortia from multiple external chal-
biopolymers mixture, including mainly polysac- lenges, such as antibiotics, and allow the long-
charides, proteins, lipids, nucleic acids, and other term existence of biofilm community. EPS not
substances from the environment or host only provides a structural framework for biofilm
(Fig. 2.1) [62]. As the immediate microenviron- but also keeps the homeostasis of microenviron-
ment surrounding cells, EPS serves various func- ment. This relative stable and interactive space
tions through the entire life cycle of biofilm. The offers chances for bacteria to survive and even
parameters of EPS include molecular concentra- persist in cruel conditions.
tion, charge condition, quantity, hydrated level,
components, and so on. These factors, varying Biofilm Formation
because of the embedded cells, stages of biofilm, The life cycle of surface-associated biofilm is
nutrient sources, and local environment/host, are well studied in in vitro models. The process is
essential for EPS functions. promoted by all different members in the com-
Mechanically, EPS provides architectural sta- munity, regulated by associated genetic networks,
bility for the biofilm entity, helps bacterial cells and also influenced by the environment. Different
adhering to surfaces, immobilizes cells onto local standpoints are taken in recent study models of
substratum, and finally forms a three-dimensional biofilm development, such as developmental
network that supports the biofilm cells. genetic regulation network, environmental adap-
Metabolically, at the extracellular retention space, tation, and multispecies interactions.
EPS helps the external substances such as oxygen The most accepted model describes the biofilm
and carbon source to diffuse into the biofilm, as formation as a highly regulated spatiotemporal
well as the internal metabolic waste moving out. process. The formation of biofilm is generally
From the multicellular and polymicrobial features summarized into five dynamic stages as (1) loose
of biofilm, EPS is also an external metabolism attachment of planktonic cells, (2) irreversible
system containing free enzymes, metabolites, adherence, (3) microcolony formation, (4) mature

Fig. 2.1 The composition of
extracellular polymeric
substances of bacterial
biofilms. Bacteria in the
mature biofilm are embedded
in an EPS matrix, which
consists of polysaccharides,
proteins, extracellular DNA
(eDNA), amyloid fibers and
bacteriophages, etc.

This polymicrobial fea- proteomics and genetic network of gram-negative ture makes interspecies interaction an important bacteria Pseudomonas aeruginosa (P. distribution cess of biofilm is sequentially regulated [181. P. especially for formation [57. At the biofilm have indicated that the developmental pro. and [114]. actinomycetemcomitans for further secre- biofilm-associated-protein (Bap) family is impor. Stages 3 and 4 of its biofilm formation quorum sensing regulatory system. The biofilm mode of survival has profound fusion [159]. emphasizes genetic pathway involvement in the In nature. For example. [229]. the underlying planktonic cells attachment. whereas distinct mechanisms gen Aggregatibacter actinomycetemcomitans. buffer ability against various challenges from the tate the vertical growth of community. desic- bution. For survive and thrive in harsh environment compared instance. that of in vivo biofilm. (5) biofilm formation from mature mac.2 Biofilm and Dental Caries 29 macrocolony formation. ple. mutualism. no evidence indicates the So far. aeruginosa biofilm is one of the earliest depend on various factors. we still have a lot to ask about the involvement of Bap in the P. aeruginosa) factor and variable in biofilm formation. Several hypotheses on the driving forces for biofilm formation. resulting environment. phagocytosis [125]. putida.1. The environmental adaptation model sug. (4) formation of macrocolonies. nutrient accumulation. aeruginosa biofilm mechanisms of biofilm formation. Therefore. fluorescens and P. early stages of biofilm formation. facilitating further communities build- nutrient availability of inner layers. This model describes the changes in importance for prokaryotes in both the natural population and structure from the perspective of environment and human body. microbial communi- colonies.1. surface structures. For exam- involve type 4 pili-mediated mechanism [109]. tion of complement-resistant protein ApiA that tant in adhesion and transition from reversible to can limit host complement-mediated killing irreversible attachment in P. metal toxicity [201].4 Survival Advantages of Biofilm gests that the phenotypic or species heterogeneity The biofilm form of growth with its surface asso- within the biofilm is the response to the spatio. such as ultraviolet exposure [56]. cation [231]. and (5) dispersal. (3) formation of environment and also a substratum for microbes microcolonies where outer cell layers restrain the to grow on. 195]. Here the how biofilm gains beneficial phenotypes and suc- developmental stages can be sketched as (1) ceeds have been proposed. even for strains from Peroxide produced by S. 159]. (2) initial seed cells surface offers a relatively stable space within the growth with sufficient nutrients. a great portion of biofilm is com- group level development. The environmental adaptation should also be included developmental model of biofilm focuses on the in the biofilm-specific gene network as described regulated transition through the cascade and above. conversely. where ties in biofilm mode gain protection and higher some cells express high level of EPS and facili. Second. First. Recent studies on the posed of diverse species. in the improvement of nutrient and oxygen distri. LapA from the by A. and roles of different bacteria and/or fungi 196]. oxygen and carbon gradient is one of to the planktonic form. reside in different bacteria. The genes that regulate the nized as the most successful forms of life on the . 2. metabolic cooperation exists between oral The general dynamic processes can be identified commensal Streptococcus gordonii and patho- in most species. channels form to further assist inner nutrient dif. gordonii can be utilized the same species. and interaction of gradient and heterogeneity showing within each cells in proximity. 137. fluctuating pH [230]. There is a long way to go Environmental impact is crucial to biofilm to find out whether the discoveries from in vitro formation. where structures like pores and and antimicrobial agents [69. and antibiotics rocolonies. thereafter ing. such as metabolic and most studied in medical microbiology field requirement. environmental adaptation models are consistent with in vivo phenotypes. ciation offers bacteria remarkable advantages to temporal change in the ecological niche. model is employed to describe the biofilm forma- tion. even being recog- metabolism.

whereas the sur- sis of health and disease. oral hygiene proce- Bacterial Biofilm dures. biofilm-associated caries. On the other hand. we can speculate that biofilm as an investigated at both composition and antimicro- advantageous form of growth offered space with bial sensitivity aspects. we can summarize that biofilm is closely faces. where they directly face nasal/lung microbiome. a limited num- nature but also on and in our body. and mainly enamel or dentin. skin. moist and relatively opens to the outer environment. we will take colonization of exogenous pathogenic microflora supragingival biofilm. vaginal.1. The to colonize. earth. Oral cavity is a unique ecological niche. dents make dental plaque a highly complex and This survival advantage exists not only in the varied community. The diverse and numerous resi- deep-sea vents. identified [193]. form microcommunities called change enormously from health to disease. and so on [15]. dental plaque can be roughly divided into associated with chronic and persistent infections.30 X. largely lim- close relationship with microbes. Tooth surfaces as well as dental plaque constantly encounter different challenges 2. typical biofilm has been studied extensively. The tooth surfaces above gingival margin are nents including the oral. Here. biofilms can be found almost everywhere ome. we have recognized that we are living in cannot grow in pure culture in vitro. With the ber of fungi and viruses are also found in oral development of human microbiome project cavity. characteristics [111]. anaerobic in subgingival plaque and basal layers In oral cavity. which are in close contact with gates of cells with or without a surface. 800 phylotypes of bacteria in the oral microbi- adays. With the help of molecu- homeostasis for the primitive prokaryotes in the lar and bioinformatics techniques. gut. tooth as mineralized hard tissue of supragingival plaque to being almost aerobic provides non-shedding surfaces for oral microbes in outer layers of supragingival plaque [142]. from being bacteria on early carious lesions as plaque [18]. which are iting our investigation on their physiological termed “the microbial part of ourselves” [228]. embedded in local microbial diversity and metabolism also polymeric matrix. Attached bacteria. such as hot spring. Thus. ago were identified [82]. In environmental microbiology. more than half of oral bacteria (HMP). Each type has its own special physi- more tolerant to certain antibiotics compared to ological characteristics and relation to disparate the planktonic state. Xin et al. In recent years. faces below the gingival margin are mainly den- human microflora usually exists as sessile aggre. more than rigid and ever-changing environment. infection is most likely resulted from this impor. and so on. tin or cementum. two categories: supragingival plaque and subgin- Because bacterial biofilm is almost 1000-fold gival plaque. . dental plaque acts with long-term multispecies microbial activity actively as part of the host defense system against within dental plaque [111]. including more than 300 species. speech. for example. Notably. Apart dental plaque. The oxygen and nutrient levels are changing constantly at different sites.2 billion years develop. which tant feature [15. affecting the homeosta. As a most oral diseases are caused by or associated naturally formed biofilm. the oxygen level varies. the dynamic oral environment. have been even in extreme conditions. to demon- [145]. Furthermore. now. For In 1886. Human microbiome has several major compo. dental plaque as a from some specific pathogen-induced diseases. Black first described the accumulated example.2 Dental Plaque as a Typical from food intake. the persistence of biofilm diseases. is warm. biofilm diseases like caries and periodontal diseases fossil records from as early as 3. when the homeostasis strate the association between dental plaque and of dental plaque is disrupted. thousands of recent in vitro and in vivo biofilm According to the location of the attached sur- studies. 58]. From the standpoint of Dental plaque was the first biofilm being evolution. Like microbes in nature. From gingival tissue and relatively less fluctuant.

matrix. Protein comprises approximately 40 % of fry weight. such as diffusion of charged anaerobic to obligate anaerobic. a plethora of secretion or cell lysis. mutans offer resident community is under constant challenges or adhesion sites for S. Granulicatella. depending on saccharides in matrix are the resources that the complex genetic and environmental variations acidogenic bacteria metabolize and generate in population. The part of plaque without bacteria is the The habitats are selective for the preferable bacte. dental plaque contains two rial secretion and saliva. The structure and gram-positive aerobic or facultative anaerobic elements of matrix are influenced by coresidents bacteria. Changing with time When exposed to the oral environment. The attached bacteria on culture-based to molecular approaches. and protects the community phylotypes are more diverse. and minerals like calcium. as that of other biofilm. the predominant species are mostly further forms dental plaque. These molecules along new taxa have been discovered. extracellular matrix. For microbial community stays stable and in a dynamic example. In contrast.3 Composition of Dental Plaque takes 1–2 %. 171]. and fluoride are in varying amounts in distinct surfaces. 145. is a ronment [1. Dental plaque is highly hydrated and con- tains about 80 % water. the subgingival species/ ents and enzymes. 18. the glucan takes ple. and the local habitat. which is usually from bacte- Like other biofilms. This fluctuant balance is metabolize sucrose in matrix into glucan or fruc- achieved by heterogeneous microflora from both tan polymers which are either water soluble or metabolic mutualism and antagonism within the water insoluble (branching). magnesium. plaque [39. Actinomyces. 167. reserves nutri- and so on [1].and subgingival surfaces.1. 169].2 Biofilm and Dental Caries 31 2. Through tooth surfaces secrete macromolecules by active 16 s rRNA gene-based sequencing. promotes coaggregation. nucleic major components: microbes and the biopolymer acid. of Oral Biofilms tion. Once established. for exam- before and after food intake. In addition. while fructan tion or after brushing. mutans and lactobacilli are able to balance (or homeostasis).4 Spatiotemporal Development varies for different hosts and bacterial composi. mainly streptococci. which is an ria that are able to grow. Neisseria. 94. 221] will shift. the tooth surfaces are . EPS contains high ratio of the approximal plaque had an intermediate micro. host cells. This matrix aids bacteria to adhere to tooth Abiotrophia. In a locus with or bioreactive molecules. faces. Prevotella. The poly- highly varied from person to person. stances develop into a complicated three- In normal microflora on fissures and smooth dimensional network that surrounds cells and surfaces. When the habitats change greatly and tant in the development and progression of dental affect local microbial activities. and gingival crevice. Staying in a relatively open niche. The bacterial species varies significantly at phosphate. extracellular polymeric matrix. approximal surfaces. The insoluble car- community. smooth sur. polysaccharides and also acts as a virulence fac- bial constitution [146]. from facultative from external harms. Besides keeping the features of both supra. lipid. and intake sub- physiological characteristics are largely unknown. the personal acids to initiate further caries progress. although their with salivary proteins. as soon as a few seconds after the tooth erup- 10–20 % of plaque dry weight. The anatomy and biological features in the local envi. the homeostasis caries [10. and a new microbial composition may be established to fit new environmental conditions.1. Rothia. The studies of microbial biopolymeric mixture of various components composition of biofilm have been shifting from from multiple sources. S. 221]. variable that reflects plaque status. surface. such as pits/fissures. mutans and thus are impor- invasions. Veillonella. It can be considered as a cies include Gemella. The biochemical constitution of dental plaque 2. the bohydrate polymers produced by S. Other common spe. based on the different essential component of biofilm [18. Capnocytophaga. Fusobacterium. local homeostasis. The dental microflora is tor in the pathogenesis of dental caries.

Xin et al. sucrose concentration increase. receptors in acquired pellicle. Hence. oralis and munity. from this community-based lifestyle. future residents. the bacterial metab. bacteria in plaque are less sensitive forming potent cell aggregates in vitro [164]. the acid produc- ment and proliferation go on. as on [150. coaggregation has been extensively interactive needs. The receptor polysac.and eases such as dental caries. 168]. start glycoproteins are essential for initial biofilm for- to absorb and attach loosely to the film by a wide mation and bacterial growth. teins and glycoproteins. Driven by environmental cues. inter. efficient metabolism through mutualistic inter- charides on the cell surface of S. plaque community. In this dynamic cells colonize following their own nutrient and process. The dental plaque as a microeco- and bacteria/host receptor interaction is often system can offer a wide range of habitats for based on protein-carbohydrate (lectin) reaction diverse microbes and integrate different resi- and eventually leads to the construction of a more dents into a highly organized and tolerant com- stable and diverse network. These molecules attach on tooth the major local source of amino acids. In some cases. coated with a conditioning film consisting of pro. leading to the numerical predominance of S. 190]. in a single site. dental plexity of biofilm composition and structure is plaque would shift to pathogenic biofilm with ever growing. Taken together. With the involvement of more species. Microbial tion and biodiversity flourish. Salivary proteins and bacterial species. including amylases. and so substances from endogenous nutrients. Within an immediate contact. 155]. a few ingredients for bacteria. proline-rich mostly saccharolytic and able to utilize metabolic proteins. whereas diet intake has a minor role in nutrient cle is recognized as the sign of the initiation of contribution due to its limited surface contact dental plaque formation [18. This film is called The quorum sensing regulatory pathway plays a acquired pellicle. tion will rise and further cause the homeostasis olism changes the microenvironment in favor of shift. the sources of which are mainly critical role during the development of dental saliva and gingival crevicular fluid (GCF) [100]. inner-species communications become active. when diet change induces local cleaning in vivo [83. studied as one of the major mechanisms in early pH. future colonizers to bind. time and unavailability of some highly complex Following acquired pellicle formation. histatins. oral Actinomyces oris are one of the most studied pair bacteria have better chances to conduct more of coaggregation partners. and a gradient of nutrient. As the biofilm develops. In contrast. statherins. This typical bacterial adhesin nity [20. mostly Streptococcus spp. proteins. 213]. mucins. S. Electron micros. whereas host food range of nonspecific and relatively weak forces. As the initial attach. activity and thus initiates oral infectious dis- With community multiplication. 31]. more mutans and finally dental caries [100. air.g. the com. With the support from extracel- act with type 2 fimbriae on A. mitis and S. 88]. lysozymes. starting the cascade of biofilm prolifera. is continuously available. actions [170]. 68. early colonizers with surface adhesins or recep. distinct microbial composition and metabolic more than 50 different species can be found [1]. and partners gradually forms in the commu- biofilm succession. oral bacteria are surface. . oralis can inter... oris surface. acquired pelli. S. maturation and dynamic transition of biofilm. surfaces and offer bioactive sites that facilitate and glycoproteins. ora. As lis) bear specific surface-anchored proteins previously mentioned. 210. bacteria produce biopoly- (adhesins) to form irreversible binding with host mers to build the matrix during biofilm formation. to inhibitory agents and host defenses [93. the metabolism with salivary copy has shown that cocci can be detected on substrates induces minor change to the local enamel surfaces at as early as four hours after pH. Selective salivary components absorb to the tooth In supragingival plaque. In health biofilm. lular matrix. intake and other activities enormously affect the These initial colonizers (e. Saliva.32 X. dental plaque as a typical tors interact and attach to the initial colonized biofilm possesses the social traits and benefits bacteria.

” paper.2 Microbial Etiology of Dental microorganisms can convert carbohydrate into Caries acid and eventually result in the demineralization of teeth and development of dental caries in sus- 2. A Sumerian text from 5000 [16. known as the father of ies site and named it S. has laid the foundation for our modern BC describes a “tooth worm” as the cause of car. and fusiform bacteria.2. Keyes The microbes sketched in his notebook are now revealed the infectious and transmissible nature known as some of the most abundant bacteria of dental caries [108]. Clarke was unable to demonstrate Around 1680. [67]. D. Miller was arguably one of the most impor. India. observed and Since 1950.3 Dental Plaque as the Cause Disease of Dental Caries W. Then in another elegant resided within oral cavity. In 1960. by a single type of already signaled the complexity of the oral streptococcus that had been isolated by Clarke microbial community [91]. he proposed a “chemoparasitic” of its microbial composition. The living microor- identified the “germs” responsible for tooth decay. mutans.” by Black and Williams ogy of dental caries. These fascinating strated caries induction in an animal harboring a observations at the birth of microbiology had “conventional” microflora. Later on.2 Dental Caries as an Infectious 2. a Dutch dry goods merchant. Clarke first iso- gradually rejected by the European medical com. In the first front teeth…. Miller’s chemoparasitic theory. which are now commonly There is a long history of understanding the etiol.2. Early Stage together with the description of “gelatinous microbic plaques”. and Japan.2. Pierre Fauchard. more than 30 years ago [61]. which was modern dentistry. One of the early achievements in oral microbiol- tant scientists who substantially advanced the ogy is to link dental plaques to dental and peri- knowledge of dental caries and associated studies odontal diseases.2 in glucose broth [38]. knowledge of dental caries etiology. Dental plaque was one of the in oral microbiology. The “tooth worm” theory has also been Due to the limited bacterial isolation and cul- described in the literature of ancient China. paper. both Erdi theory of dental caries. As a practicing dentist with first substances van Leeuwenhoek examined a comprehensive training in natural sciences. ganisms recorded by him revealed for the first In his 1890 book titled Microorganisms of the time the complex nature of dental plaque in terms Human Mouth. Miller was unable to identify the causative Enlightenment. Unfortunately. detrimental to the teeth and gingiva. various experimental animal described first microorganisms in the tartar from models have been employed to better elucidate his teeth with his primitive microscopes. During the European Age of tury. 2. van Leeuwenhoek (1632–1723) that this organism actually caused caries. which suggested that oral and Ficinus described the presence of .1 Oral Microbiology at ceptible hosts. Fitzgerald and Keyes successfully demon- chetes. lated a bacterial species from human dental car- munity. two important arti- for three days and then took the material that has cles were published which were considered the lodged in small amounts on the gums above my cornerstone of dental caries research. the “tooth worm” theory was agent(s) of dental caries. 219]. tivation technique available in the nineteenth cen- Egypt. ies.2 Biofilm and Dental Caries 33 2. using hamster as animal model. spiro. including cocci. I found a few living animalcules. known as “dental plaque. In 1924. was one of the first to oppose capable of fermenting several sugars and produc- the “tooth worm” theory and noted that sugar was ing a pH of 4. In his the nature and etiology of oral diseases. including notebook. he under his microscope [67]. he recorded “I didn’t clean my teeth dental caries [105].

the oral “pathogens” such as S. mutans and vice versa. while S. While The oral microflora has been recognized as one there is little doubt about the ability of S. mutans. microbial targets. underscored the impor. mutans by J. cated with caries. teeth [197]. S. the normal flora. K. streptococci (including S. in which den- tant role of dental plaque in the etiology of dental tal caries is the result of the overall interaction caries and has become one of the essential para. mutans was recog. tion of [16] paper. it is clear that there are individuals and metagenomic studies. Hence. mutans Unlike many known medical pathogens that are published in 2002 further stimulated numerous “foreign invaders with specific virulence factors. with low levels of S. Researchers in this field proposed that the viru. these species.6 Ecological Plaque Hypothesis terial species present in the mouth (aciduricity).5 Nonspecific or Specific Plaque [16]. the “nonspecific mutans with Dental Caries plaque” hypothesis has been challenged for decades. However.” studies of this bacterium at genetic level.” a gela- tin-like substance that carried microorganisms 2. The complete genome sequence of S. mutans. mutans were not definitive at the level of individu. An alternative view is that among the Considering the involvement of S. Numerous studies suggested focusing studies on the control of specific a positive correlation. recognized as dental pathogens. microorganisms within the “membrane” on the to cause dental caries in humans or animal models. the association is not unique. mutans resides in three core attributes. However. the rat caries model and the positive correlation of S. (ii) to produce large quantities of organic ease. over 700 bacterial species population groups of high caries susceptibility have been identified from the human oral cavity.2. mutans of the most complex microbial communities in . However. and (iii) to toler- ate various environmental stresses. particularly low pH which are toxic to most of the other bac.4 Association of Streptococcus not be absolutely right. caries can be considered as specific. of all the groups of bacteria within plaque. mutans in the 200–300 indigenous species identified in the pathogenesis of dental caries as demonstrated by oral cavity. together with Miller’s Miller’s “chemicoparasitic theory” proposed a chemoparasitic theory. treatable tal caries by the detected number of S. in such circumstances. mutans can persist with- including the abilities (i) to metabolize dietary out evidence of detectable demineralization. Black’s work. caries can occur in the apparent absence of lence of S. mutans are part of the correlations between dental caries and S. cricetus) are strongly impli- of the cariogenic abilities of S. in which he referred dental plaque as “gelatinous microbic plaques. the full implications of its contribution to the pathogenesis and progres- dental plaque were not realized until the publica. sion of dental caries is still unclear. and S. This proposal had the benefit of present on the teeth.2. dental miologist tried to predict the development of den. sucrose to form insoluble polysaccharides that Indeed. Hence. Xin et al. mutans are implicated with dis- faces. acids (primarily lactic acid) from a wide range of the debate is still ongoing up until today. mutans with dental caries in most cases suggested that this proposal might 2. non-S. epide. From the initial isolation of S.2. Today. S. 2. Thus. Clarke in 1924 to the latest als. mutans infections.34 X. only a finite number of them can be early in vitro and in vivo animal models. Due to the imperfection of both theories. “nonspecific plaque” hypothesis. some acido- mediate the persistent colonization of tooth sur. efforts were gradually shifted to the exploration sobrinus. although Mutans nized as the chief culprit of dental caries. digms of oral biology. and S. genic. Black believed that bacteria within dental Hypotheses? plaque generate acids that dissolve the dental hard tissue. rattus. carbohydrates (acidogenicity). However.

further supporting the tantly. Data obtained from metage. ity is a highly heterogeneous ecological system Actinomyces. mitis. ties of a biofilm. essential nutrients and cofactors for with sound enamel [110. obligate anaerobes). potential. made up of over 1 × 1014 cells. niches such as the oral cavity. instead of the presence or licle on the surfaces of teeth/dentures and other absence of specific groups of microbes. community structure and metabolic function of nance by acidogenic/aciduric gram-positive bac. caries. a recent study on salivary The first stages of dental plaque formation microbiome of caries-active population further involve the attachment of bacteria to salivary pro- supports the ecological hypothesis that the shifts in teins and glycoproteins that are deposited as pel- community structure. the mouth is continuously nomic level favorably support the ecological bathed with saliva at a temperature of 35–36 °C plaque hypothesis. S. including S.25. redox The introduction of high-throughput metage. S. para- 2. Veillonella. Cavity Actinomyces. In addition. different microbial communities. gut. and S. Bacteria that first attach to the sali- to the occurrence of dental caries [232]. and containing distinct niches with significantly Thiomonas in plaques were significantly associ. The nutritional condi- on microbiome in caries cavity showed that the tion of the oral cavity is often described as caries cavities are not dominated by S. and only a few taxa were genic populations in plaque correlate with dental present across the whole populations [231]. but it is the interactions between The different key ecological factors present in the biofilm residents that are crucial.2. suitable for colonization by more fastidious spe- flora has been currently proposed as a novel cies (e. More impor- ated with dental caries [42]. and vagina. Leptotrichia. Moreover. contribute oral tissues.. oralis. as well as an appropriate pH. hesion). The data support the polymicro. As proposed by Phil Despite the continual shift of these microor- Marsh in his “ecological plaque hypothesis. of which 90 % are These early colonizers proliferate and change the microorganisms that comprise the resident local environmental conditions. mutans and lactobacilli) at the tors include appropriate receptors for attach- expense of the acid-sensitive species associated ment. the phylogenetic microbial structure idea that no one specific pathogen but rather patho.. Subsequent colonizers such as . In addition. the tooth surfaces pro- our understanding of the overall oral microbial vide distinct binding factors for microorgan- diversity and function. vary pellicle are designated primary colonizers. for example. sanguinis. The resident microflora nizers also form the base layers of complex dental dynamically interacts with the human body. varies with aging. the resident microflora. isms. In dental these biohabitats have a great impact on the caries. Take the nomic pyrosequencing has profoundly advanced oral cavity.g. nutrition. and nisms (a process termed coaggregation or coad- defense systems of the host [143]. mutans. new microbial tributing directly and indirectly to the normal cells adhere via similar adhesin-receptor mecha- development of the physiology. con. Granulicatella. further exerting far-reaching are a complex community formed by tens of bacte. 143]. A recent metagenomic study and a pH of 6. the composition of the resident not merely the presence of a single organism in a microflora is distinct in different habitats/ complex community that determines the proper. Gemella. Another investigation microflora from various oral sites of different on the oral microbiota of children with dental car. S. growth. this resident micro. and gaseous environment. Subsequently. Consistently. there is a shift toward community domi. These early colo- organ in human body. Those ecological fac- teria (e.g. our recent study by sampling bial etiology nature of caries. influence on the composition of microflora. rial species [77]. but “feast or famine”. gordonii.1 Microbial Ecology in the Oral sanguinis. Abiotrophia. plaque biofilms.75–7.6.” it is ganisms. S. It has been estimated that the human body is and Granulicatella species are often detected. making the site microflora of the host. Thus. age groups has demonstrated that the oral cav- ies revealed that genera Streptococcus.2 Biofilm and Dental Caries 35 the human body [122]. Veillonella.

structured. tion is one of the most robust associations with ment) and nature factors (host genotype). which have substantial influence on the proper- species biofilms. dental caries). a recent report by individuals have revealed significant inter. the tooth morphology is heavily determined stable over time. (ii) synergistic interactions Host immunity plays an essential role in for the growth or survival. neutralization of a virulence factor produced by sialoperoxidase. the microbial ties of dental plaque.6. and human genotype. Previous studies in healthy populations [193]. cultural traditions. “war and peace” is dental plaque. Fermentable carbohydrates The viability of oral microbial community is are the class of nutrients that most affect the dependent not only on the host genetic and envi- microbial ecology of the mouth. indicating that the host genotype such diet. lactoferrin.2 Genetic and Environmental oral microbiome cannot be simply classified into Factors and Oral Microbial nurtural or natural.g. structure and function of the human oral micro- biome. They are catab. and inducing micro- ment of acidogenic/aciduric species within the bial pathogenesis. inhibiting most of the species between the microbial residents.6. ronmental factors but also on interactions olized to acids. Moreover. Nevertheless. such usually used to describe the dynamic microbial as oral hygiene. gingivalis are especially tissues surrounding the oral cavity may secrete effective in attaching to earlier plaque colonizers antimicrobial agents and immune modulators. and this microbial homeostasis to be influenced by genetic factors also contrib- is intricately maintained by the dynamic intermi.g. sIgA). (iii) antagonistic inter- shaping oral microbiome. and (v) interference in the adaptive immunity (e. Frequent exposure to low pH can disrupt extensively. The residents in while promoting the growth of aciduric organ. bacteria for nutrients. most factors involved in the diversity in 2. will interactions within a biofilm. proposed the philosophy of shared environ- community structure of the oral microbiome and ment serving as the main determinant of microbial its influencing factors. bial interactions include (i) competition between ota [143]. [205]. Therefore. as race and ethnicity may also be one of the major gender. Nurture (environ. Accumulating evidence from Ecology twin-pair model favors the “environment domi- In order to fully understand the change of oral nates” theory. and eventually form complex. In fact. Other environment factors. geography. the complex oral microbial community interact isms. antimicrobial peptides) and another resident. actions by secondary metabolites production.g.. several recent studies have sug- Diet is one of the most important environment gested that ethnicity tunes the oral microbiome at factors that impose profound influence on the more specific levels [147. multi. hygiene. and geography. Once established. Host other [122]. micro- also influence the composition of oral microbi. 239]. . age. By comparing the composition varia- microbial community during the occurrence and tion of salivary microbiome in a cohort of 27 development of oral diseases (e. medication.. Xin et al.. In general. forming biofilm structures. carrying microbial homeostasis and lead to the enrich.36 X. utes to the community structure of human oral crobial and host-microbial interactions [143]. work together to determinants for the human microbiome diversity shape the oral microbiome [164].2. Fusobacterium and P. can directly growth-dependent signaling mechanisms of each inhibit some exogenous microorganisms. out physiological functions.and the Human Microbiome Project Consortium has intraindividual structure and function diversity in shown that the ethnic or racial background associa- the human oral microbiome. Saliva contains com. monozygotic and 18 dizygotic twin pairs. microbiome [143]. such as microbiome.2. lysozyme. Stahringer it is necessary to completely characterize the et al.3 Interspecies Interactions diet exert strong selection on the composition of and Dental Caries the oral microbiota. (iv) ponents of innate (e. Exogenous nutrients provided via the 2. In addition to host immu- composition of dental plaque remains relatively nity.

cal antagonism between these two bacteria in the Interactions mediated by signaling molecules oral cavity has been noted for decades. mutans UA159. so the flux of mutacin-encoding genes have been annotated in glucose to lactate increases. As lactate is removed from the immedi. S. mutans with tems to detoxify hydrogen peroxide [117. naeslundii and petitors. for the negative correla- faces [168]. mutans in the oral cavity corre- are capable of expressing certain pathogenic fac. The onization and high levels of S. which lacks effective sys- genic/aciduric organisms such as S. bacteria including A. at least nine other putative ate environment by Veillonella. tion of the presence of S. mutans produces a number of distinct biofilms. mutans favors the Hence. On the result of the presence of S. be responsible. sanguinis and S. Similarly. mutans metabolizes sucrose to generate acid bacteriocins often have a narrow killing spectrum more efficiently compared to other common oral and inhibit the growth of related organisms [178]. addition to antagonism. are also prevalent in the dental biofilms. In addition. growth of itself relative to that of other less acidu- erally recognized that this disease is not solely ric oral streptococci including S. organisms which are able to actions Metabolic interrelationship is one of metabolize oxygen would favor the growth of the most common interspecies interactions nearby anaerobic organisms [46]. eages of bacteria. sanguinis [132]. isms such as lactobacilli and Actinomyces species high levels of S. Rather. it is now gen. Similarly. sanguinis and thus may form extensive biofilms on saliva-coated sur. Animal tors. Bacteriocins are nutrients provided by other organisms as well as proteinaceous toxins produced by all major lin- polysaccharides present in dental plaque. late with low levels of S. A dynamic balance of both synergistic and study has also demonstrated a so-called competi- antagonistic interactions with the coresidents tive exclusion between S. sanguinis. S. mutans may take advantage of the sub. streptococci and a variety of oral sumed. One of the best examples is dents may determine which organisms are between S. delayed colonization by S. growth of S. suggesting a ing growth of streptococci [155]. it is the crobial hydrogen peroxide to antagonize the net result of the interaction of multiple acido. mutans and S. isms. Unlike traditional antibiotics. sanguinis in an quorum-sensing regulatory molecule autoin- infant’s oral cavity correlate with significantly ducer-2 (AI-2) is a potential signaling molecule . 119]. growth. in part. Bacteriocin is another key factor involved in able from the periodic intake of food. The ecologi. The lactic acid produced by S. S. For example. in the case of dental caries. coresidents in these structures. sanguinis plays an essential role in determining whether depending on the sequence of inoculation [156]. S. metabolic products of one organism may promote the growth of other organ- Factors Involved in Interspecies Inter. 175]. oralis in metabolizing salivary components to inhibit the growth of S. “arsenal” against its competitors. bacteria [83]. In other commensals within the dental plaque. 174. mutans and other caries-associated organ. Nutrients could be avail. In addition. the expres- also have effects on other coresidents within the sion of bacteriocins by some other biofilm resi- same biofilms. In oral cavity. mutans The secondary metabolites of one organism in the dental plaque [81]. different bacteriocins (mutacins I to V) produced cocci is utilized directly by Veillonella for by S. actinomycetemcomitans strate competition and acid selection to emerge produce bacteriocins that are lethal to other bac- as a predominant resident in caries-associated teria. large repertoire that can be used against its com- ple is the combined efforts of A. lactate produced by strepto. mutans have been identified [36. mutualism between two bacteriocins (also known as mutacins) as an organisms dependent on nutrients is also com. Early col. When sucrose is frequently con. the genome of S. At least five mon. mutans. within dental plaque. For example. these pathogenic factors cause damage or not. mutans and S. Another exam. sanguinis can produce antimi- single organism in dental plaque. mutans. sanguinis. and the interspecies competition. Some of these bacteriocins are able to S. saliva. thus in turn enhanc. mutans or any the other hand.2 Biofilm and Dental Caries 37 S.

and virulence factors of the oral microbial cariogenic S. AI-2 functions as one of the pri. In addi- acid-sensitive commensal species (e. Xin et al. mutans) at the expense of the of related noncariogenic streptococci. mutans. oralis and A. a prote. some coresidents such as among different species within the same biologi. one of the involved in interspecies interactions. gordonii can inactivate the CSP community and thus are involved in the onset and produced by S. sanguinis. The quorum- the oral microbial community. organisms. between heterogeneous bacteria within biofilms. In the case core cariogenic virulences of S. S. AI-2 also mediates mutualistic biofilm the other hand. gingivalis and S. for example. gordonii acids by metabolizing carbohydrates. On addition. the oral microbial community. mutans. S. present in the biofilm could indirectly exert pro- tal biofilms tune microbial composition. the interaction with the dental individual organisms or groups of related microbial community can not only affect the . mutans interactions. The CSP-induced numeric predominance of acidogenic/aciduric bacteriocin production also modulates the growth bacteria (e. sanguinis/S. CSP caries. naeslundii strains petitiveness and prevalence of S. ability to produce large quantities of organic ase (i. In addition to AI-2. challisin) expressed by S. some commensal bac- Taken together. The aforementioned factors play an generate alkali to neutralize the acid. S. the CSP-mediated quorum-sensing systems nis) associated with sound enamel [110. mutans may acquire trans. properties of oral residents. including S. tion. (niche). signal by the competence cance on the occurrence and incidence of dental stimulating peptide (CSP). is highly species specific and is not likely to Bacterial interactions could also affect the interfere with the activity of another distinct CSP overall expression of bacterial virulence of the molecule.g. thus achieving a great genomic diversity for bet- bial community structure is characterized by a ter environmental adaptation. Changes of these sensing systems also modulate the virulence factors can perturb the established equilibrium. 143]. mutans regard. sangui. modulate the virulence of these biofilms.38 X. struc. For example. microbial homeostasis can only teria such as Veillonella are able to consume the be achieved when an equilibrium is established lactic acid. Therefore. these two bacteria may have ecological signifi- donii. In this inhibits CSP-dependent properties of S. gordonii vs S. mutans by [177].e. found effects on the biofilm virulence. Bacterial interactions can affect the growth of In conclusion. this reestablished micro. In hydrogen peroxide under certain conditions. thus modulating the composition of One typical example is that the luxS mutants of P. biofilm residents which The Role of Interspecies Interactions in Dental could affect the levels of the regulatory molecules Caries The interspecies interactions within den. mary mediators of interspecies interactions sanguinis [238]. mutans utilizes leading to the emergence of newly predominant CSP-induced bacteriocin production to acquire bacteria more adaptive to the microenvironment transforming DNA from other coresidents [118]. In dental caries. metabolism of either urease by urease or arginine tions within biofilms. sanguinis can cal niche. but a mutation in either strain alone generating S. S.. S.. and S. biofilm. many of resulting from the dynamic competition between the oral streptococci. S. S. mutans ratio within oral biofilms. and S. mutans by producing cytotoxic allows for such a biofilm formation [153]. gor. through the essential role in modulating interspecies interac. mutans [149]. gshAB is essential for the com- formation by S. its presence could thus progression of dental caries [122]. coresidents which are capable of neutral- [215]. Hence. forming DNA from the coresidents through the mutans tend to reduce the cariogenicity of the CSP-induced bacteriocin production [118]. mutans is the of S. The S. In addition..g. In dental biofilms. are involved in the antimicrobial resistance of S. izing/depleting the acidic end products of S. thus shaping the structure of by arginine deiminase system [26]. Unlike the AI-2. gordonii. In addition. the CSP still can be indirectly biofilm. Since non- ture. mutans. detoxifying hydrogen peroxide produced by S. S. salivarius. Take S. Of note. gordonii cannot form mixed sanguinis gained competitive edge over mutacin- biofilms.

i. mostly through cates a correlation of sugar with dental caries.2 Lactobacilli 1850.3. Hence. Among those acidic microbial metabo. period. macaca. However. Dental caries is ferus. and S. including (1) processing adhesins for dental caries has been linked to the two largest initial attachment to the saliva-coated tooth sur- dietary shifts in human evolution in terms of the face. rattus. plaque. lactic acid has been identified as the major bacteria. a sudden expansion of caries lesion Lactobacillus is a genus of gram-positive faculta- occurred coinciding with the introduction of tive anaerobe or microaerophilic rod-shaped bacte- refined flour and sugar due to industrial revolu. further enriching acidogenic and aciduric lites. and consumption of domesticated grains positively (3) the production of organic acid to generate correlates with a marked prevalence of caries. destruction of dental hard tissue. thus influ. until the late nineteenth century. cricetus.1 Streptococcus mutans 2. After 2. With charide. infectious disease resulting in the localized mutans.2. lactoba- dietary substrates contribute to the development cilli are poor colonizer of smooth tooth surface. The pandemic of butes. fructan. Mutans strepto- cocci are a group of most important bacteria Dental caries is a multifactorial and chronic highly associated with caries. below virulence properties of oral residents. 158]. when Miller evi. the acidogenic bacteria are recognized as 2. sobrinus. S.3.1 Carbohydrate Metabolism cocci are commensal bacterial but can and Acidogenic Bacteria opportunistically initiate caries. S. downeii.0 after continuous sugar exposure plaque and suppress the acid susceptible microor- [194]. glucan. acidic microenvironment and promote enrich- However. It is gram-positive facultative coc- cus commonly arranged in chains. Actinomyces is a genus of gram-positive faculta- The accumulation of organic acids leads to con. who exacerbate the initial enamel lesion to deep dentine reported that microbial metabolism of carbohy. The interspecies interactions have eco- logical significance in the occurrence and pro- gression of dental caries. the homofermentative metabolism. of dental caries [157. 2.3 Dental Caries-Associated S. lesion. mutans was first described by J Kilian Clarke Bacteria in 1924 [38]. Lactobacillus count “culprit” of the dental caries remained enigmatic has been used to assess caries activity for years. Although the epidemiological history indi. (2) the production of extracellular polysac- consumption of fermentable carbohydrates.e. ria. S. After colonizing into the established dental drate in dental plaque could drive the local pH plaque. to facilitate retention the advent of Neolithic farming.3.3. the increased on tooth surface and plaque accumulation. the lactobacilli can further acidify the values below 3. tive or strict anaerobic pleomorphic rod-shaped . Lactobacillus is acid tolerant and can carry out gly- denced that the acidic microbial metabolites from colysis at pH values as low as 3.2 Major Acidogenic Bacteria 2. the degree of caries was mild and preva- lence remained relatively stable until 1850. consisting of S. Oral strepto- 2. Lactobacillus is able to convert lactose and tion. other sugars to lactic acid. lactobacilli are generally believed to were further confirmed in 1940s by Stephan.2.2 Biofilm and Dental Caries 39 growth of certain species but also modulate the tinuous pH decline to the critical pH.. Their cario- one of the major disease burdens inflicting genic virulence mainly involves several attri- humans throughout history. contributor to the pH decline in dental plaque. S.3. S. ganism. across the Neolithic and medieval ment of aciduric microflora.2.3 Actinomyces the culprit for caries initiation and progression. which tooth hard tissue demineralization begins encing the overall pathogenicity of the dental and dental caries gradually occurs [143]. These observations Therefore.

0. roughly equivalent to those in serum.0 in less than 20 min 2. suggesting tolerance involves global cellular response. To survive and proliferate nine.5. 2. Alkali in acid conditions. an in. Actinomyces spp. naeslun. may also be extruded from cyto. Alkali generation is particu- genic biofilm. Taking S. DNA protection/repair system. These subunits assemble into (αβγ)3 oligo- . which would eventually lead to the enrichment of acidogenic/ The central pathogenesis of dental caries is the aciduric bacteria and continual acidification of production of organic acid and the resultant the dental plaque favorable for caries formation. in root caries is still protein for damaged protein. A. thus increasing solic pH favorable for normal enzymatic function plaque pH [33. can oral biofilm. mutans cell cannot grow at pH values lower 10 mmol/L.0 to 3. β. increased activity of sketchy. The cariogenic Protection bacteria emerge as numeric predominant species during this acidification process. Overall. and urea (Fig..3. In addition. bacteria. consisting of α. decalcification of dental hard tissue.3. especially A. Xin et al. than 5. and oral haemophili. agmatine. ureC. The primary source of alkali pro- also function better and carry out glycolysis at duction is through microbial metabolism of argi- low pH values of 3–4. the acid tolerance mechanisms allow the cario- 2. As a saccharolytic and acidogenic bac. Acid tolerance In addition to the aforementioned acid tolerance or acidurity is the most important attribute for mechanisms. apy against caries (Fig.3.2). by at least seven genes arranged as operon in plasm by a membrane carrier for lactic acid. including alteration of metabolism. changes in mem- brane fatty acid composition. which involves iogenic microflora and thus provides a promising both constitutive acid tolerance and acid-induced/ strategy for the development of ecological ther- adaptive tolerance [25]. alkali generation is widespread those acidogenic bacteria to prevail in a cario. quorum sensing system. ATP generated by glycolysis to pump out intra. including S. Moderate role in modulating the microbial ecology within acidophile. The adaptive acid caries lesions and sound root surface. mutans. In this case. the in saliva and crevicular fluids ranges from 3 to S. regulation of depth knowledge about the involvement of indi. naeslundii. The dental plaque undergoes rapid.4 Base Generation and Caries upon carbohydrate intake [102].40 X. However. 129].0. especially Lactobacillus spp. ureA.1 Urease example. the cariogenic bacteria have generated by these metabolism pathways might developed a large repertoire of strategies to main. their association with root caries. and γ sub- adaptive acid tolerance response indicates the units. although the glycolytic pathway can The physiological concentration of urea present catabolize sugars at pH values as low as 4. Urease is a nickel ion- and cellular viability. ance mainly relies on the F-ATPase proton pumps in the cell membrane. synthesis of chaperonin vidual Actinomyces spp. lactate. by urease to ammonia and CO2. can convert urea cellular protons and thus maintain neutral cyto. neutralize the acid metabolites produced by car- tain intracellular homeostasis. at a pH as low as pH 3..3).4. dynamic pH fluctuations ranging from pH 7. thus most bacteria. [148]. The urease apoenzyme. etc. Constitutive acid toler. salivarius. for 2. Acidogenic bacteria such as S.0 after exposure to a sub- dii. has been frequently isolated from both root lethal pH of approximately 5. 2. dependent multisubunit metalloenzyme encoded olite. and ureB encode the maintaining a relative neutral cytosolic pH. larly important for the survival of acid-sensitive mutans can function better at pH 6 and can even commensal bacteria and thus plays an important carry out glycolysis at pH below 4. the end metab. among oral species. the F-ATPase will use the Some oral species.3 Acid Tolerance of Acidogenic genic bacteria to outcompete other acid-sensitive Bacteria coresidents under acid selection. induction of enhanced survival ability of bacteria terium.

The expression of bacterial urease is encode chaperone complex essential for the regulated by multiple environmental cues. ing low pH. [131]) meric complex with six nickel ions incorporated sette transporter. Dental biofilms in a healthy host maintain a micro. growth [32]. Alkali generation by biofilm commensals remineralization of dental hard tissue. carbohydrate availability. and source. and ureI encodes urea trans- into the active site. limited nitrogen center. eventually results in the initiation and/or progression of bial and pH homeostasis with a balanced demineralization/ caries lesion. encode a Ni2+-specific ATP-binding cas. 2. such as ureM.2 Biofilm and Dental Caries 41 Urease Urea + H2O 2NH3 + CO2 Ornithine carbamoyl. the presence of urea. 2. The continuous plaque acidification tion.3 The role of alkali generation in caries preven. ureF. ureE. Other genes.2 Summary of alkali-generating pathways in the oral cavity (Figure is reproduced from Liu et al. may enrich the edge of acidogenic/aciduric bacteria. ureQ. [131]) Oral environmental Low pH Neutral pH stresses Enamel Caries Oral alkali generation Health Disease Oral commensals Acidogenic and aciduric bacteria Fig. . Liu et al. Ornithine Carbamate kinase Arginine deiminase transferase Arginine Citrulline Carbamoyphosphate NH3 + CO2 + H2O NH3 ADP ATP Arginine decarboxylase Pi CO2 Putrescine carbamoyl- Agmatine deiminase transferase Agmatine Carbamoyl putrescine Putrescine NH3 malolactic enzyme L-malate L-lactate + CO2 F1F0 ATPase H+ ATP Fig. ease the competitive cues. and ureD porter [32]. includ- incorporation of Ni2+ and CO2 into the metallo. and rate of ureO. dental hard tissue. such as frequent sugar exposure. The environmental can directly neutralize plaque pH. ureG. and restore a healthy acidogenic/aciduric bacteria via acid selection and further microbial equilibrium (Figure is reproduced under the lead to plaque acidification in favor of demineralization of permission of Dr.

AguD including S. AgD activity is generally lower ADP to generate ATP.4. as well Lactobacillus salivarius and release ornithine. Arginine is abundant in salivary secretions as ammonia. The putrescine carbamoyl- arginine catabolism by ADS generates ATP. 2.4 Alkali Production and Biofilm (AgDS) Ecology Agmatine present in the oral cavity can be Dental biofilms are complex ecosystems with obtained from foods. S. encoded by aguB. ComDE. such as rice. CO2. S. indicating the ecological ing CiaRH. which hydrolyzes arginine to generate generated can also be used in exchange of agma- citrulline and ammonia.75 mmol in dental agmatine at low pH favors the growth of these .3.3. and in the opposite orien- line to ornithine and carbamoylphosphate. encodes agmatine-putrescine antiporter to allow sanguis.4.2 mmol in saliva [76]. and beer. naeslundii [99]. gordonii has been tal stresses. On the contrary. also involve in involvement of ADS expression in multispecies the induction of AgDS genes under low pH or biofilm. milk. In S. ADS has L. The abil- nine decarboxylase enzymes. and CO2. hundreds of metabolically and physiologically or be produced from arginine by bacterial argi. the agu operon in S. arginine. located upstream of. the presence of agmatine and other environmen- In addition. ammonia. Finally. mitis. [74]. AgDS may not be sufficient to porter (ArcD) that is encoded in the same operon. further metabo- which could be further utilized to counter acid lizes N-carbamoylputrescine to yield putrescine stress through both constitutive and adaptive acid and carbamoylphosphate. Unlike urea hydrolysis by urease. carbamate tolerance pathways. or concentration of agmatine is 0. ADS. 2. para. Arginine is nus. many oral bacteria. sanguinis. tine via the antiporter [74]. Agmatine is System (ADS) primarily metabolized by AgDS to putrescine. and NH3. and some oral is then hydrolyzed to N-carbamoylputrescine and spirochetes have been also identified as argino. uberis. downeii. ADS expression is induced by arginine and by elevating the cytoplasmic pH and generating low pH. kinase encoded by aguC gene transfers a phos- encoding genes are commonly arranged in an phate group from carbamoylphosphate to ADP operon [47. which is thine carbamoyltransferase. Xin et al. cricetus. encoded by aguA. mutans. other oral streptococci. Certain Lactobacillus and Actinomyces the entry of free agmatine into the cell.4. and arginine aminopeptidases and transcriptional accumulating evidence has indicated that AgDS regulators are often encoded in ADS gene clusters may actually favor the acid tolerance of S. The physiological ity of oral species to metabolize urea. which converts citrul.3 Agmatine Deiminase System 2. arranged in operon (aguBDAC) [74]. mutans. phase dependent. encodes gene encodes carbamate kinase that transfers a a transcriptional activator of agu genes [75]. and S. diverse species competing for nutrients. thermal stress [130].2 Arginine Deiminase plaque and 0. Multiple two-component systems. S. and ammonia. 136]. sobri- tal saliva around 50 mmol/L [211]. ADS activity in S. Similar to urease. S. The putrescine deiminase. includ- with A. mutans [235].3. AgDS activity is growth catabolite repression (CCR) and can be downreg. gordonii. Agmatine species. mutans. CO2. including low pH and heat shock reported to be upregulated when it coaggregated [75]. The operon is also sensitive to carbon extra ATP. S. and ATP. transferase. rattus. aguR gene. brevis [76]. AgDS is also encoded by genes been identified in many commensal bacteria. Many relative to that of arginine deiminase or urease organisms also possess an arginine/ornithine anti.42 X. arcB gene encodes orni. AgDS is present in polypeptides with average concentrations in duc. arcC tation to. In phosphate group from carbamoylphosphate to oral streptococci. and VicRK. and it can also be induced by ulated in response to elevated oxygen levels [48]. including S. Therefore. counter the plaque acidification. arcA gene encodes arginine to generate ATP. ammonia by the agmatine deiminase enzyme lytic [26. 141]. S. and primarily metabolized by the microbial ADS to S. CO2.

55]. orchestrates the status of oral health and disease. S. 3. Significantly higher levels of salivary ADS esis of dental caries [144]. caries.3. The “ecological plaque hypothesis” cantly higher than healthy population are more further proposes that the bacterial consortium in the resistant to caries.5 % argi- relatively lower level [76]. [116.3. In the meantime. the plaque pH above the critical pH after a dents benefit from the local alkalization by sucrose challenge [216]. reversing early carious lesions compared with it enhances the acid tolerance of these acidogenic dentifrice containing 1450 ppm fluoride alone bacteria by neutralizing cytoplasm acid and gen. mutans expressing the urease genes hypothesis” supports the concept that caries is the from S. it directly increases the pH of den. dental plaque can interact in complex synergistic bohydrate intake [172]. forming complex ecology system [45]. also been proven more effective in arresting and nificantly alkalize the dental plaque. such as S. that arginine-containing oral hygiene products gens S. an ammonia generated from arginine or urea break. and venting the overgrowth of cariogenic bacteria Bifidobacterium dentium as the potential cariogenic (e. . On the other hand. and Pseudoramibacter genera shown negative correlation with the development are also indicated as bacteria associated with caries and progression of caries. frequent exposure to car- compared with those of caries-free individuals bohydrate) that eventually lead to the net pathogen- [211]. 188]. activity of alkali generation of oral biofilm has Propionibacterium. the “nonspecific plaque strain of S. Scardovia wiggsiae and Slackia exigua. increasing number of clinical trials have shown down [48]. Consequently. The contributions of ADS. sobrinus probably cannot sig. Toothpaste containing 1. urease and ADS can protect the bac. resistance [160]. the caries patho. Firstly.5 Clinical Relevance of Alkali Production The oral cavity is inhabited by hundreds of bacterial Alkali production holds the promise to be a species. The addition of arginine- teria from excessive environmental acidification bicarbonate to mouth rinse effectively can raise [33].4. els are also positively correlated with caries resis- urease. cific bacteria. In addition. The “specific pathogen hypothesis” has led to the alization. and antagonistic fashion.g.5 Other Caries-Associated Bacteria 2. subjects with dental caries. other less-aciduric coresi. and AgDS to oral biofilm pH homeostasis tance [163. A longitudinal study on children and microbial ecology can be quite different. In contrast. mutans) dependent on acid selection. gordonii. A genetically modified progress [173]. The promising strategy for the management of dental interplay between oral microflora and the host caries. salivarius showed potent anticaries consequence of the overall acid production activity effects in a rat caries model [37]. Atopobium.. erating extra ATP.. The genera.2 Biofilm and Dental Caries 43 bacteria by cytoplasm alkalization. but instead. Consistently. activity and plaque urease activity have been tion of ATP could further enhance acid tolerance reported in caries-free population compared with by providing energy for proton extrusion. Secondly. and it is the structure and resistant subjects have higher ammonia function shift of the microbial community driven by concentrations and resting pH in their plaque environmental cues (e. tal plaque in favor of dental hard tissue reminer. despite their high dietary car. Olsenella. mutans and S. mutans or S. AgDS nine and 1450 ppm fluoride in a calcium base has of S. Chronic renal of the total plaque microflora rather than a few spe- failure patients with salivary urea levels signifi. The pathogens [199]. thus promoting the prevalence of these bacteria during the development of caries. salivarius and plaque urease is correlated with dental caries S. Salivary arginine lev- or maintenance [75]. growth. More importantly. sobrinus have no urease or significantly reduced the incidence of dental car- ADS but possess AgDS that is expressed at a ies [2. 192. 2. In has further validated that ammonia generation by some oral commensals. 234]. alkali generation favors the identification of several other species including persistence of healthy commensals while pre.g.

and it acts bac. 114. gels and varnishes and thus disrupt the microbial equilibrium within . Chlorhexidine is one of the most tested antiplaque Fluoride can disrupt enzyme activity and reduce agents and represents a gold standard against acid production by oral bacteria [84]. When chlorhexidine binds to microbial in subgingival plaque [11. [218] have and form [4]. or causes leakage of cell constituents [95]. Chlorhexidine binds [107] and stannous fluoride [151] can be bacteri- strongly to most bacteria and surface structures in cidal at higher concentrations against oral bacte- the oral cavity. The man. a comparable efficacy initiation and progression is diverse. 202]. period of tooth development can cause dental The efficacy of chlorhexidine mainly depends fluorosis.4. The usually prescribed dos- of Dental Caries age for chlorhexidine mouthrinses has been 10 ml of a 0. Fluoride is a dual 2. in particular to restore the microbial dis- equilibrium within the oral biofilm. 21]. it destroys the surface structure. Mouth rinses. Amine fluoride in a gel formulation can mucous membranes which are negatively charged inhibit the growth of mixed bacterial populations (anions). chlorhexidine is bacteri. and it is now recognized as the major contributor to the dramatic decline in car- ies prevalence worldwide [28].4 Antimicrobial Approaches are some of the most often used delivery forms of to the Management chlorhexidine [191]. 59]. milk and salt) or cidal. At The methods of fluoride delivery are either higher concentrations. Although the tents. than 70 years. 2. sprays. can also achieved [59]. In addition. Chlorhexidine molecules are within dental plaque [20.44 X. rinse possesses a transient antibacterial effect teriostatically when administered at low concen.2 Fluoride is to provide an overview of various antimicro- bial strategies applied in dentistry and related Fluoride has been applied in dentistry for more studies. It disrupts normal membrane functions bacteria. tively suppress the growth of commensal bacteria cation.2 % solution. with twice-daily Dental caries is a biofilm-mediated disease. Xin et al. but no clear antiadhesive activity against oral trations. Chlorhexidine exhibits broad antibacterial role of fluorides in caries prevention represents spectrum with gram-positive microorganisms one of the most successful stories in general pub- particularly sensitive than gram-negative lic health. shown that the amine/stannous fluoride mouth- Chlorhexidine is a strong base. gels. applications and mouthrinses) [59]. Chlorhexidine also possesses very good Preincubation of hydroxyapatite with amine flu- substantive properties [139].4. including tooth surfaces and ria. fluoride could nonselec- on the concentration and the frequency of appli. 24]. Amine fluoride positively charged (cations).12 % composition of the biofilm associated with caries chlorhexidine mouthrinse. By using 15 ml of a 0. acting on both tooth hard tissue and oral microbes [58. supplements. agement of dental caries is to target the dental plaque. sanguinis to glass conditioned with either precipitation of cytoplasm causing cell death [59]. effect of chlorhexidine can be retained for up to sobrinus in biofilm in vitro [183]. varnishes. The antimicrobial oride can significantly decrease the growth of S. systemic (water. thus sup- which the potency of other antiplaque agents is pressing the enrichment of cariogenic bacteria compared [8. leading and tin fluorides can also inhibit the adhesion of to an osmotic imbalance with consequent S. Of note. Amine fluoride cell walls. The mouthrinses. saliva or bovine serum albumin in vitro [54].1 Chlorhexidine functional anticaries agent. This section 2. excessive fluoride intake during the microorganisms. 12 h or longer depending on the delivery dosage in vivo data reported by Weiger et al. paint-on cell constituents and precipitation of cell con. inducing leakage of low molecular weight topical (toothpaste.

brackets. This is also surface-active agents with a wide antimicrobial due to the nonleaching properties of the material. over the past decades due to its antimicrobial Quaternary ammonium polyethylenimine (QAS- property. similar to those polyca. Previous study tionic agents. The typically used concentration (W/V) PEI) nanoparticles were incorporated in restor- of CPC is 0. maximize the anticaries benefits while minimiz. and properties. Therefore. without alteration of the original mechanical 223]. simi. 2. and body This divergence may be attributed to the monoca. S. It interacts with microorganisms via cationic binding. has presented that adhesive system containing Cetylpyridinium chloride (CPC) is a com. The antiplaque effect of CPC was first ties [12]. . products such as deodorants. salivarius are susceptible to low concentra- assessed [59].07) have also been used [44. Although CPC shows equal or better antimicrobial activity against planktonic Triclosan is a nonionic antimicrobial agent being culture compared to chlorhexidine. to con. 2. such as orthodontic adhesives. although slightly higher con.2 Biofilm and Dental Caries 45 the dental plaque. sanguinis. 222. poration of 1 % QAC-PEI nanoparticles in dental Research has demonstrated that CPC mouthrinses composite resin has a strong antibacterial effect have antiplaque activity when used alone or in against S. released or lost over time by copolymerizing with the resin through the formation of a covalent bond with the polymer network [209]. a systematic review has further properties [13]. casei when incorporated in con- The CPC molecule allows ionic and hydro.and gingivitis-inhibiting also reported to have antibacterial effect against effect of CPC-containing mouthrinses [87]. More recently.4 Triclosan lar to chlorhexidine. 98. ative materials to increase antibacterial action centrations (≥0.4. triclosan has been tionic nature of CPC [53]. ventional glass ionomer [14]. QACs are immobilized in the composite and not ing the risk. It has been demonstrated that the incor- reported by Schroeder and Hirzel [79. mutans and can sustain over 1 month conjunction with toothbrushing [79. Triclosan is active against both gram-positive trol caries lesion formation around orthodontic and gram-negative microorganisms and fungi.4. since leaching leads to increased water absorp- 123]. Although CPC retains its antimicrobial Oral bacteria such as S. 182]. QACs has similar antibiofilm properties and last- monly used QAC in a variety of mouthwashes ing at least 6 months of water aging [237]. gevity of these materials [227]. phobic interactions since it belongs to both hydrophilic and hydrophobic groups. At low concentrations. S. decreasing the clinical lon- cytoplasmic leakage. QACs deliver their antimicrobial activity tion and solubility and decreased mechanical by binding to the cell membrane and causing properties with time. but phylactic agent with the purpose of reducing den- CPC is cleared from the oral cavity more rapidly tal biofilm formation and the development of [17]. 140. the clinical effect remains to be S. it exhibits an used for more than 30 years as a preservative in inferior inhibitory effect against biofilm [59]. cautions should be Polymers containing QACs have also been taken in the application of fluorides in order to incorporated into dental materials [34. mutans. 80. mutans and L. 236]. powders. Therefore. without further reduction on mechanical proper- 214]. soaps.05 %. QAC-PEI nanoparticles were validated the plaque. Initial retention of applied to dentifrices and mouthrinses as a pro- CPC is higher than that of chlorhexidine. CPC could be incorporated into dental gingivitis [59]. materials. spectrum against both bacteria and fungi [64.3 Quaternary Ammonium the dental material has a durable and long-lasting Compounds antibacterial capability without significantly dis- turbing the biologic balance in the oral cavity and Quaternary ammonium compounds (QACs) are material’s mechanic properties [96]. 35. Recently. tions of triclosan in vitro.

the widespread use of claims of xylitol over other polyols [59]. and environmental microorganisms prophylactic effects of xylitol or superiority [233].4. properties of triclosan have been demonstrated in which are believed to be less virulent than xylitol- both in vitro and in vivo studies [78.4. Triclosan and amine fluoride also mechanisms suggest that xylitol is a promising show combinatory antibacterial and plaque. tions by specifically inhibiting bacterial lipid mutans by impairing their polysaccharide forma- synthesis which further impairs cell membrane tion. Xylitol inhibits the growth of several bacte. All the aforementioned 186. chew- reduced susceptibility to triclosan after repeated ing itself promotes secretion of saliva and thus exposure to sublethal concentrations of this caries prevention. further well- agent.5 Xylitol Listerine. Anticaries effect of xylitol has Although triclosan is bactericidal at high concen. Bacteria could develop Besides the antimicrobial effect of xylitol. . agent to substitute sucrose in chewing gums. Xylitol is an alternative sweetening dentifrices leave residues that will dilute to sub. In addition. reducing effect in vivo [6]. 233]. Xin et al. mutans appear to be pared to chlorhexidine and thus lacks profound the specific target [19. sensitive strains [207]. triclosan may also lead to the development of concomitant resistance to other clinically impor- tant antimicrobials through cross-resistance or 2. been reported in longitudinal xylitol dentifrice trations. A number of studies have verified the designed randomized clinical studies with proper occurrence of triclosan resistance among dermal.46 X. 101. 176. triclosan is bacteriostatic [59]. has been demonstrated in a number Xylitol is an effective tooth decay-preventive of clinical studies to possess moderate antimicro- pentitol accredited to its non-acidogenic prop. mutans plaque inhibitory effect [53]. Although studies regarding the concomitant resistance to other Phenols. as a surgical antiseptic in the 1860s [220]. lethal concentration. 71]. Long-term consumption of xylitol also pro- synthesis [152]. bial effect against dental plaque [43. erty. controls are needed to validate the caries- intestinal. 208].7 Natural Products way. mutans and reduces the amount of plaque and the number of Natural products offer a wide variety of structur- S. Listerine has poor oral retention com- rial species. among which S. The antimicrobial/antiplaque motes the selection of xylitol-resistant S. can suppress the critical cariogenic factor of S. The S. cautions should been known to be bactericidal since Lister used it be taken on the widespread use of triclosan [59]. More importantly. Triclosan func. mutans in both the plaque and saliva of xylitol ally different substances with a broad range of consumers [203]. 198]. Phenols are able to reduce plaque accumulation when used at high concentrations [63. which is an essential oil/phenolic mouthwash. However. uptakes xylitol via a constitutive transport system specific for fructose and enriches xylitol intracel- lularly as a non-metabolizable metabolite. Xylitol has been incorporated as an active The major concern of the widespread use of ingredient in dental hygiene products. xylitol inhibits the growth of S. xylitol caries therapies [104]. However. which could be applied into bacterial metabolism and consequently halt the the development of alternative or adjunctive anti- pH drop in the dental plaque. Xylitol is able to disrupt the biological activities.6 Phenolic Antiseptics coresistance mechanisms. have antimicrobials are still limited. In this 2. such as triclosan-containing products is the possibility of xylitol-containing dentifrices currently available inducing antimicrobial resistance [124. either alone or in combination. triclosan-containing products such as studies [189]. on the market. cariostatic agent in controlling dental caries. 133. 135]. mutans. 2.4.

Wu-Yuan et al. mutans. 185]. flavonols (pinobanksin-3-acetate). Essential oils have also been extensively There are many other reports available con- investigated for their antimicrobial activity cerning the anticaries properties of various other against caries-related bacteria. odorous and volatile products of plant secondary [126] have identified that gallotannins from metabolism. are typically a complex mixture of Melaphis chinensis and triterpenes (ceanothic approximately 20–60 compounds that are in acid and ceanothetric acid) from Ceanothus solution at various concentrations [104]. against S. Thymol and eugenol inhibit the taining gallic acid and methyl gallate) can growth of a wide range of oral microorganisms inhibit the growth of S. Essential oils related organisms. Catechins inhibit the growth of S. 180]. tea) against caries-related bacteria has been growth of S. dihydro- catechins. polyphenolic [179]. Another study catechins at sub-MIC levels further support the of sanguinarine mouthrinse and toothpaste carried translational application of tea extracts in vivo. rupting the integrity of the bacterial membrane Ginkgoneolic acid from Ginkgo biloba has also and cause the rapid efflux of intracellular bacte. followed by aromatic and aliphatic con. 97] and increase pro- compounds” (e. acidurity. 89]. studies by our group have also demonstrated that Sanguinaria canadensis [73]. although they are not antibacterial by themselves. reduce plaque by 57 % when given for 6 months MIC levels [228–230]. many of the “flavor bacterial cell membrane [41. tt-Farnesol is particularly [200]. [225] and Li et al. naeslundii. in particular (−)-epigallocatechin gal. ton permeability [103]. and terpenoids late (EGCg) and (−)-epicatechin gallate (ECg). Specific flavanones (pinocembrin). The application of propolis extract on rat Accumulating evidence has indicated that the molars also reduces the severity of carious lesions bioactive components of green tea. plant extracts. and paste regime has been shown to significantly extracellular polysaccharide synthesis at sub. genic agent which exhibits antimicrobial activ- Propolis is a natural composite balsam collected ity against S.. Sanguinarine is a benzophenanthridine alkaloid might act synergistically with the abundant cate. which might destroy the integrity of concentrations. mutans at high 98 % of microbial isolates from human dental concentrations but also suppress cariogenic fac. Essential oils. characterized extract of Galla chinensis (con- stituents [9]. plaque [49]. Furthermore. Propolis not only inhibits the (i.e. originated from the alcoholic extraction of pow- chins to suppress bacterial growth [120]. mutans cells [113].2 Biofilm and Dental Caries 47 The antibacterial effect of Camellia sinensis beeswax [66. out in 120 subjects showed 13–17 % lower plaque considering the substantivity of these active com. 185. 184. sobrinus with MICs ranging between 50 and biofilm-associated S. [65]. A sanguinarine mouthrinse and tooth- tors involved in the acidogenicity. using both in vitro and in vivo presses the production of bacterial polysaccharides models [165. mutans and suppresses specific by bees from tree buds and mixed with secreted virulence factors associated with its cariogenicity . A. which are within the concentra. nerolidol) in green tea. (tt-farnesol) are believed to be the bioactive compo- are able to inhibit the growth of the streptococci nents of propolis [112].. 228–230]. ated with its lipophilic property and membrano- Catechins are also bactericidal at even higher tropic effect. been shown to be a potential natural anticario- rial components [185].g. 166. within biofilms [226]. Recent dered rhizomes of the blood-root plant. 6-month treatment period [115]. rhamnosus and appear to act against bacterial viability by dis. could not only concentration of 16 μg/ml could completely inhibit inhibit the growth of cariogenic S. mutans and other caries- including S. including L. particular EGCg. a chemically noids. mutans and S. Sanguinarine at a tea catechins. In addition. mutans [184. The and 1000 μg/ml. The americanus possess antimicrobial activity main active component of essential oils is terpe. antibacterial activity of tt-farnesol is likely associ- tions determined in brewed tea [106. The bioactivities of tea during orthodontic treatment [86]. sobrinus but also sup- widely studied. mutans effective against the proliferation of both planktonic and S. scores compared with a placebo group after a ponents in the oral cavity after tea consumption.

More importantly. By performing metabolic function analyses on none isolated from Rheedia gardneriana. and genes identified via metagenomic approach. have been evaluated in clinical trials [104]. 7-Epiclusianone. researchers are able to retrieve information both cyanidin A2. bioinformatics. of DNA amplification. Using permeability of S. By pyrose- application of natural products in the field of car. the Microbiome phylogenetic microbial structure varies with aging. it is still challenging to ated. species boundaries and gain valuable insight into Despite the aforementioned efforts to identify the metabolism within the community. a the natural substances potentially active against comparative metagenomic study has been initi- cariogenic organisms. and it is defined as “the appli. sequences viduals. what functions or metabolic processes are glycolytic enzymes by increasing the proton possible in that particular community [70]. and mucosal plaque) collected from healthy population at different age 2. are distinctly different between periodontal and . some cranberry flavonoids (e. to metagenomic samples [22. 16S rRNA of biological samples (i. Recently. characterized vidual species.48 X. and only a few taxa were present across The term “metagenomics” was first invented by the whole populations [231]. comparative study of oral microbiome using trolled trials is needed to further validate the metagenomics-related techniques. Moreover. pro. The differences between periodontal and healthy indi- approach randomly shears DNA. By charac- shotgun sequencing.g.. using organisms which may not have been detected rodent models of dental caries) and even fewer using currently available technologies [121]. microbiologist will be able to piece general metabolism. we have directly in their natural environments.5. terizing the phylogenetic and functional gene quencing. The Our group has been working on the implementation of standardized randomly con. [90]. glycolysis. more impor- shown to inhibit the acid-sensitive intracellular tantly. we have demonstrated that the oral cavity Dental Plaque Study is a highly heterogeneous ecological system con- taining distinct niches with significantly different 2. and A-type oligomers) have been on which organisms are present and. indicat- enhanced computational power for analyzing ing the importance of immune status in shaping DNA sequences have enabled the adaptation of the structure of oral microbiota [217]. bypassing demonstrated that ALL patients have a structural the need for isolation and lab cultivation of indi. It is anticipated that such compari- isolation procedures. and lactic acid together a metabolic network that goes beyond production of S. saliva. we have shown that the phylogenetic and many short sequences. By comparing the Handelsman [85]. mutans cells [72. supragingival plaque.5 Ongoing Direction of Oral groups. aiming to compare the microbial community determine the precise mechanisms of action and within dental plaque associated with healthy and efficacy due to the complexity of chemistry and diseased sites. such as chip-based pyrose.. mutans [23]. quencing the “hypervariable regions” of bacterial ies management. 161]. composition of supragingival plaque microbiota cation of modern genomics techniques to the of acute lymphoblastic leukemia (ALL) pediatric study of communities of microbial organisms patients with healthy controls..1 Metagenomics and Oral microbial communities. and possibly involved in systemic infections.g. 52]. A comparative genetic studies coupled with expres- crude extract of Psidium cattleianum can also sion experiments such as microarray and pro- inhibit the expression of proteins involved in teomics. Xin et al. imbalance of the oral microbiota. myricetin. and reconstructs them into functional gene structures of the oral microbiomes a consensus sequence [22]. few studies have son will assist in identifying potential pathogenic actually been conducted in vivo (e. a prenylated benzophe.e.” The advances in the refinements by reduced diversity and abundance alterations.

a variety of genes Early detection and quantification of cariogenic involved in virulence factors. it should have recently demonstrated that certain gastroin- include the detection of cariogenic bacteria and testinal bacteria. However.1 Probiotics been proved for more than 100 years. Mechanisms of probi- Laboratory which can monitor pH gradient within otic effect within the oral cavity are likely similar dental plaque with high sensitivity and in real time to those proposed in gastrointestinal studies [138]. Instead. and glycosaminoglycan and pyrimidine cians take preventive measures to stop caries degradation are enriched in periodontitis. The the health of the host [5]. In conjunc- provided new insights into our understanding of tion with nanotechnology development. elucidate the contribution of the comparative microbial difference to the pathogenesis and prognosis of oral infectious diseases and hence 2.or nucleotide-based bac- with periodontitis compared with healthy indi. will benefit the damaged tooth) via surgical approaches. recent advancement in caries pathogenesis allows which has been successful established in the us to understand that a comprehensive analysis of treatment of intestinal diseases. such as the polyaniline-based teria and thus contributed in the prevention of planer pH sensor developed by scientists at Jet dental caries. L. Experimental studies and clinical trials teeth with surgical approaches. traditional den. reuteri [30]. The introduction of microorganisms as a . Overall. [154]. casei [27]. much like early detection of cancer the genes involved in amino acid synthesis and markers before overt/detectable cancerous lesions pyrimidine synthesis are suppressed in people develop. amino acid metabo. new approaches have been developed to maintain oral biofilm homeostasis. while development. is opening a new chapter for cariology. L. Organization as live microorganisms which. and Bifidobacterium tooth remineralization [204]. and the enhancement of L.5.. the reduction of cariogenic streptococci. including elimination of cariogenic bacteria. New antibody. Bifidobacterium spp.5. these tests phylogenetic and functional gene structures of can be further developed into different forms of oral microbial communities interacting with the nanochips for the detection of multiple pathogens host. metagenomics-related oped for the detection of cariogenic bacteria in work from our group and those from others have chair-side or laboratory settings [187]. plaque acidogenicity. Such strategies are aimed to inhibit plaque bio- 2.2 Evidence-Based Dental Caries film formation without disturbing the biological Diagnosis equilibrium within the oral cavity. rhamnosus CG [162].5. tistry still focuses on treating the symptom (repair when applied in adequate amounts. More cohort studies are needed to further in the clinical settings [127]. mentioned above. instead of Probiotics is defined by the World Health treating it as infectious disease. followed by a comprehen. demineralization sites and repairing damaged 206].3. potential to alter colonization of cariogenic bac- itoring of plaque pH. terial detection techniques have also been devel- viduals [128]. Specifically. cautions should be taken Propulsion Laboratory and combined NMR con. The use of probiotics. Although the infectious nature of dental caries has 2. including Lactobacillus and plaque acidogenicity. may help in controlling the sive treatment of dental caries that includes the proliferation of oral microorganisms. The combination of DN-173 010 [29] have all been shown to have the accurate detection of oral bacteria and in situ mon.2 Biofilm and Dental Caries 49 healthy groups. when using the lactobacillus species as they can focal microscopy from Pacific Northwest National also produce acids [202]. bacteria in plaque or saliva samples can help clini- lism.3 Novel Antimicrobial Therapies provide comprehensive knowledge for the devel- opment of novel approaches to a better control of In addition to “traditional” antimicrobial agents dental caries. is now also con- dental caries should be more than detecting tooth sidered for the treatment of oral diseases [162.

where chemical agent might encounter diffusion ate adequate hydrogen peroxide so as to control limitations. Rivera LE. or modify the oral biofilm and may offer substan- oxidase effect [59]. Stokes LN. competence-stimulating peptide caries could possibly act through colonization (CSP). microbiologists are tial novel preventive light therapy against bio- now developing novel techniques and products films.5. CO2 laser (wavelength of 10. Glucose oxidase produces hydrogen per- oxide from glucose provided by the enzyme 2.43(11):5721–32. without affecting other noncariogenic commen- thetic analogues are also promising in caries sal residents [50. Wolff M. which is produced by vari. thus maintaining a balanced and bacteria [60].50 X. mutans-specific delivery of oral environment [5]. age the tooth surface. J Clin Microbiol. [134]. However. Whole saliva contains two peroxi. S. Hence.3.3 Specifically Targeted erythrosine and white light (500–650 nm) [224].3. viability of S. Light therapy could be used to reduce the growth of microorganisms via enhanced per. which limits its application One good example is the targeted antimicrobial in plaque control [60]. deep layers. CO2 may potentially dam- isms and achieve similar probiotic effects [91]. A “STAMP” is a fusion peptide with two moieties: a killing References moiety made of a nonspecific antimicrobial pep- tide and a targeting moiety containing a species. bicarbonate/calcium carbonate CaviStat-containing . Machado C. Aas JA. Xin et al.5. Acevedo AM. The success in peroxide. The activity of CO2 laser irradiation on the that do not involve live bacteria. Dewhirst FE.2 Salivary Antimicrobial cultures [50]. The addition of these Light is more effective on bacteria in biofilm enzymes to oral products is suggested to gener. eliminate pathogens while preserving the protec- thiocyanite (OSCN−) in the presence of hydrogen tive benefits of the normal flora.4 Light Active Killing amyloglucosidase. 51]. The effect of the salivary peroxi. 2. yet generate tar. Such STAMPs are potent against S.6 μm) healthy microbe-host relationship. Importantly. Olsen I. Antimicrobial Peptides Exposure of S. has been used as a STAMP targeting resistance and/or immune modulation within the domain to mediate S. tial health benefits. mutans biofilm cells can be killed by up to 3 log10 folds when treated with 2. 1. 51]. STAMPs are able to Substances eliminate S. therapy via a novel specifically targeted antimi- crobial peptides technology [50. mutans in biofilm can reach in the geted effects against pathogenic factors or organ. Hypothiocyanite is antimicrobial and the development of S. The targeting moiety Defining the normal bacterial flora of the oral cavity. these molecules act control [92]. killing domain. mutans grown in liquid as well as in biofilm 2. specific binding peptide. Kleinberg I. STAMPs specifically targeting various pathogens dase system is related to the availability of including periodontal pathogens within oral cav- hydrogen peroxide. 2005. The inhibitory effect of an arginine crobial peptide. In addition to under certain conditions is suggested as a poten- the use of live organisms. mutans from multispecies biofilms Antimicrobial substances in saliva and their syn. namely. mutans-specific STAMPs inhibits some streptococci and lactobacilli may expand further to the design of other in vitro [134]. mutans biofilm to blue light had (STAMPs) an impeded effect on bacterial viability through- The benefits of probiotics are mainly achieved by out the biofilm and a sustained antibacterial effect modulating existing microbial flora associated on biofilm newly formed by previously irradiated with the host. as “probiotic” antimicrobials that may selectively dase that oxidize thiocyanate (SCN−) to hypo. Paster BJ.3. provides specific recognition of a selected patho. ity and provides an ecological approach to the ous microorganisms as a metabolic end product management of dental caries. gen and targeted delivery of an attached antimi. A pheromone produced by S. therapeutic tool for the management of dental mutans.5.

1999. 59–67. Atlas RMBR. 33. Banas JA. 14. ella sp. Characterization of a Streptococcus sp.16(3): the composition and metabolism of a mixed culture 63–70. Hodgson R. Genomic analysis of pies for dental plaque-related diseases. 2002. 26. Sandalli N. Arweiler NB. Effect of an amine‐fluoride‐triclosan mouthrinse on Hoogenkamp M.63(6):317–20. In vitro adhe- 11. Allaker RP. 29. Antibacterial activity of Twetman S.9 Suppl 1:23–9. lism within in vitro dental bacterial communities and vary bacterial counts. Vickerman MM. 2005. The in-vitro 8.33(5):403–4. 15. tablets.14(2):89–99. J Bacteriol. Oral streptococci… products of their Biological effects of essential oils – a review. Gjermo P. Yudovin-Fearber I. Buzalaf MA. 1978. 24. Ergeneli S. Marquis RE. genesis in Streptococcus salivarius 57. Bansal G. Mahaffy JM. faces by lactobacilli from a Bio–Yoghurt. Weaver CA.17(7):414–8. J Antimicrob Chemother. Microbiol Lett. Addy M. streptococci and lactobacilli in young adults. Wilson M. J Clin Periodontol. Antonucci JM. nanoparticles against Streptococcus mutans. ten Cate JM. Wilson M. cellular matrix formation of cariogenic biofilms. Machado C. Benjamin/Cummings Science Publishing. Wolff M. Brighenti F. Kraigsley AM.46(2):446–75. Cisar JO.33(1):8–13. Dual functions of 23(4):289–94. J Clin Dent. Domb AJ.28(4):251–6. Glucan-binding proteins bacteria and protection against dental caries. et al. Antibacterial activity of dental composites Mechanisms of action of fluoride for caries control. Caries Res. Lin NJ. Delbem A.32(6):456–62. Mead D.36(2):81–6. New York: 31. viability. Identification and charac- chlorhexidine and some quaternary ammonium terization of the nickel uptake system for urease bio- compounds with regard to retention. FEMS of the oral streptococci. Breitbart M. 1990. Dekker H. 1994. Averbeck D. 2003. Koo H. Jenkins S. Biofilm infections.22:97–114. 21. Luppens S. editor.77(3):445–52. J Bacteriol. Marsh P. Food environment.64(5):314–8. 2002. Van der Mei H. 17. Newcombe R. Caglar E. J Dent Res. 6. J Clin cattleianum leaf extract on Streptococcus mutans Periodontol. 23. Burne RA. Burne RA. 2008. Bullock S. Biology of Streptococcus 182(16):4667–9. 1997. Kolenbrander Springer Science + Business Media. 2003. Blacks conclusions reviewed again. 2002. Dr. Bowen WH. 1991. 2008. Chen Y-YM. Caries Res. Ergeneli S. Alkali production by oral 10. Kavaloglu S. Int J Antimicrob uncultured marine viral communities. 30. Streptococcus salivarius urease.99(22):14250–5. Effects 4.41(10):827–35. 18. Domb AJ. 9. Takeuchi Y. Beyth N. Bradshaw D. Anti-plaque agents in the effect of an amine fluoride gel on subgingival plaque prevention of biofilm-associated oral diseases. Montero M. Selvi S. 2006. 2006. Newman H. Henning G. Microbial ecology.190(24):8145–54. Chalmers NI. Averbeck S. The survival of sion to enamel and in vivo colonization of tooth sur- subgingival plaque bacteria in an amine fluoride‐con. Effect of yogurt with 13. Effect of Psidium plaque regrowth and biofilm vitality. editor. 2011. Reich E. of oral bacteria grown in a chemostat. Rojas-Sanchez F. Baehni PC. The effect of of glucose and fluoride on competition and metabo- some chlorhexidine-containing mouthrinses on sali. protein expression and acid production. Visser J. 1998. 25. et al. Twetman S. Effect of sugar alcohols on Venezuelan school children. cles. Proc Natl Agents. Oral bacteria. Pessan JP.23(1): Dis. Bradshaw D. J Nanomater. Acad Sci U S A.. J Bacteriol. Menlo Park: Caries Res. 5. dren. mutans-derived glucosyltransferases: role in extra. centration and plaque-inhibiting effect in the human 2003. Quintessence Int. A comparison between 32.19(1):1–8. Bonesvoll P. 2009. 2000. 20.27(21):3995–4002. Deng D. Bakkali F. Caries taining gel. Douglas CW. Andresen B. Beyth N. 1989.2 Biofilm and Dental Caries 51 dentifrice on the development of dental caries in 19. Bahir R. Burne RA. Odontol. 2000.42(2):148–54. Rivera LE. Cheng L. 2008. biofilms. Biomaterials.185(23):6773–9.193(1):1–6. et al. Arch Oral Biol. 2009. to inhibit the development of dental caries in chil. salivary con. containing quaternary ammonium polyethylenimine Monogr Oral Sci. 7. Salamon P. Clinical eval. 2005. Honorio HM. Antibacterial amor- Caries Res. 2012. Bifidobacterium DN-173 010 on salivary mutans Long-term antibacterial surface properties of compos. rium Lactobacillus reuteri ATCC 55730 by straws or 2012:58. 18(2):90–3. 3. Weiss EI. 12. Bjarnsholt T.45(1):69–86. Bradshaw D. J Clin Dent. Weiss EI. LLC. Kavaloglu Cildir S. Netuschil L. et al. Palmer Jr RJ. Burne RA. PE. Black GV. 2011. 1898. phous calcium phosphate nanocomposites with a . Caries Res. 2008. Analysis of pH–driven dis- uation of the ability of CaviStat in a mint confection ruption of oral microbial communities in vitro. 22. Marsh P.29(4):358–63. Acevedo AM. Sandalli N. Mulder A. Xu HH. Acta Odontol.40:440. Beyth N. I. Acta ite resin incorporating polyethyleneimine nanoparti. Busscher H. Chen YY. Idaomar M. Chem Toxicol. Marsh P. 34.-Veillon- 16. Newman H. 27. mouth after mouth rinses. community micromanipulated from dental Dent Cosmos. 28. 1998. Weir MD. Res. Salivary mutans streptococci and lacto- dental cements containing quaternary ammonium bacilli levels after ingestion of the probiotic bacte- polyethylenimine nanoparticles. Weiss EI. Novel anti-microbial thera. Pilo R. Çaglar E. plaque. Segall AM. J Clin Periodontol. Crit Rev Oral Biol Med. 2011. Yudovin-Farber I.

Embleton J. 2363–9. 2004.61:9–19. 46. Complexation. 2008.83(1):18–25. 1999. Mayer M. Gest H.8(9):623–33. Oral Microbiol Immunol. analysis of functions involved in adhesion of Clin Microbiol Rev.42(4):572–85. Epstein SR. Comparative in vitro activ. J Bacteriol. Zaura E. Adv Dent Res. 187–201. Plant products as antimicrobial agents. Clancy KA. Zhang K. Burne RA. Exploring the oral micro. Chemotherapeutic inhibition of supragin. bial activity against periodontopathic bacteria. Br Dent 37. antibiotic from Streptococcus mutans. 2011. J Microbiol.51(6):336–8. Kidd E. Anderson MH. Cowan MM. Konings WN. Clarke J. Peterson DM.5:141–7. 48. Zhou X. Targeted killing of Streptococcus mutans by a Hooke and Antoni Van Leeuwenhoek. Fitzgerald RJ. 2010. 67. BMC Genomics. Light therapy complementary antibac- Periodontol. Salivary composi- dental caries. Qi F. Genetic 41. 2001. Gebara EC.284(5418): 2001. Niehaus C. Cole MF. Chen T. Caufield PW. J Bacteriol. 1960. Pseudomonas putida to seeds. Microb Ecol. 2007. Mandel I. terial treatment of oral biofilm. Höfling. Flemming HC. 2004. cariogenicity. of persistent infections. Fejerskov O. Crielaard W. the natural car- biota of children at various developmental stages of ies repair process–the need for new approaches. Burne RA.16(3):182–4. Pearson S. 1999. 2006. Braz Antimicrob Agents Chemother. J Clin 60. N-Methylolverbindungen und über die Einwirkung nine deiminase system from Streptococcus gordonii von Formaldehyd und sekundären Basen auf Isatin: DL1. Rodriguez-Brito B. 38. fluoride inhibition of Streptococcus sanguis adhesion tionship between dental plaque ureolytic capacity and under continuous flow. Rogers AH. treatment to re-establish a healthy microbial flora for 35. Wegley L. Meiller TF. a bactericidal ogy. Periodontology: antibacterial agents in the Agents Chemother. 44. 2009. logic role of streptococci in experimental caries in 45.28(5):561–72. Costerton JWSP. On the bacterial factor in the etiology of 55. Infect Immun.148(Pt 2):467–72. Remineralization. Overholser CD. Snyder JA.182(9): 42.81(5):117.68(11):5549–53. Cheng L. control of supragingival plaque—a review. Yu the hamster.J. BMC Med Genom.186(6):286–96. Dzink JL. Tanner AC.33(4):365–9. Featherstone JD. Dent Mater. Keyes PH.27(4):663–5. Targeted antimicrobial nanoparticles. 2012. gival dental plaque and gingivitis development. the chemical and microbial composition of dental 56. Socransky SS. Br J Exp Pathol. Izard J. 2000. Dental caries: the disease and 43.10:251–6. Dong Y. . Zilm PS. Über einige Additions-und Konden- 47. Bowen WH. S. 2012. 57. Lindhe J. 50.16(5):311–5. Espeland EM.39(12):2656–60. Scand J Dent Res.50(11):3651–7. Lima LA. Driessen AJ. J Dent Res. N. Wingender J. 1975. Schuller AA. et al.68(5):2621–9. long-term protection.4:22. Characterization of recombinant. 1980. W-H. Control of expres. Chen Y-YM. Haynes 2012. Montijn RC. Eckert R. 63. its clinical management. tion and calculus formation in patients undergoing 39. Yarbrough DK. 2000.58(2): Antimicrob Agents Chemother. Burne RA. Dent Res. 58. Bacterial biofilms: a common cause implications for biofilm microbiota. Appl Environ Microbiol. 1975. Xin et al. J Bacteriol. Melo MA. 49. Wetzel RG. Feuerstein O. Rev Odontol Univ Sao 186(8):2511–4. M. ureolytic 54. Huse SM. Antimicrob 53.24(2): Xu HH. Diaz PI. Scopp IW.24(2):103–7. Demonstration of the etio- Hyg. 2002. Dewhirst FE. Keijser BJ. Paulo. stabiliza- plaque in the monkey (Macaca fascicularis). Chikindas ML. Fusobacterium nuclea. J Dent 61. Shi W. Dong Y. 1989. 1908. and UV photolysis of extracellular and surface- Res. Paster BJ. Effect of listerine on tum supports the growth of Porphyromonas gingivalis dental plaque and gingivitis. Weir MD. Royal Society.54(3):449–57.12(4):564–82. Sullivan R. Göttler M. Notes Rec R Soc Lond. 1318–22. Fornell J.192(19):5002–17.91(6):598–604. J Periodontol. 1995. 2002.. Bowen WH. Science.7:57.52 X. Mayer M. Hoboken. Microbiology. Propolis antimicro- ity of sanguinarine against oral microbial isolates. Using pyrose- 36. Newman H. The discovery of microorganisms by Robert Shi W. Sundin Y. quaternary ammonium dimethacrylate and silver 51. bound glucosidase and alkaline phosphatase: 40. The biofilm matrix. In vitro study of the sion of the arginine deiminase operon of Streptococcus antimicrobial activity of natural substances against gordonii by CcpA and Flp. Nat Rev Microbiol. 1924. J. et al. ments. Effect of sodium phytate on hemodialysis. He J. Breitbart M. Anti-biofilm dentin primer with quaternary 94–7. 66. Eckert R. 1999. 2006. Safety and efficacy of 2012. 2010. Ramos JL. mutans and S. Spolarich AE. 62. DePaola LG. Mutacin II. 64. DePaola LG. 65. Wilson M. Adv their dentition in the relation to their oral health. 1985. Edwards RA. Amine and tin Streptococcus mutans demonstrates an inverse rela. Espinosa-Urgel M. The human oral microbiome. Eley B. Chen Y-YM. quencing to shed light on deep mine microbial ecol- Schilling KM. fellows of the pheromone-guided “smart” antimicrobial peptide. Adv Dent Res. Wiley-Blackwell. ammonium and silver nanoparticles. J Am Dent Assoc. sobrinus. Novak J. Salido A. Zardetto C. in oxygenated and carbon-dioxide-depleted environ. Isolation sationsprodukte der Halogenacetamide und ihrer and molecular analysis of the gene cluster for the argi. J Dent tion. 2002. Gebara E. antimicrobial mouthrinses in clinical practice. 59. 1996.21(1):4–7. Minah GE. 52.

2005. J Pharm Pharmacol. Shapiro periodontitis. Hamada S.58(2):147–53. Analysis of caries development.16:655–62.137(12):1649–57. The bactericidal properties of the qua- diseases. Veerman inase system in mutans streptococci. The effects of Immunol. Giertsen E. ria in the subgingival microflora of adult patients with 78. Gasparovich SR.2(2):95–108.101(1): an agmatine deiminase gene cluster in Streptococcus 110–5.69:660–7. biofilms. Rosalen PL. J Ethnopharmacol.38:S6–10. Childs 3rd WC. Hotz P. 1980.80(1):363–70. Wu T. discussion mixed-genus community: stabilized arginine biosynthesis 682–663. Gross EL. Grenby T. 2012. Allison DG. 2005. 1990. Carbohydrates in 79. 69. Berchier C. Hannah J. Vickerman MM. Jakubovics NS. 90. Science. Gibbons RJ. Clardy J. Jacobs WA. Long-term clini- and in vivo: do singular mechanisms imply cross. 2010. 2002. 72. 2009. J Dent.1(2):47–58. Koo H. Eckburg PB. review. rial aggregating activity from whole saliva and den- nicity. Haps S. Molecular biological access to the adhesion to oral surfaces. Nascimento MM. J Clin Periodontol. Characteristics of cranberry phenolics on glucan synthesis by glucos. Tagg JR. Int J Dent Hyg. McBain AJ. Imazato S. 92. tal plaque. human distal gut microbiome. J Am Dent 95. FEMS Microbiol Lett. mouthrinses. The 71. Slade HD.6(4):290–303. 2009. in Streptococcus gordonii by coaggregation with .103(5):1960–8. Microbiol infections. 94. and biofilm of Streptococcus mutans nase system of Streptococcus mutans UA159. Bacterial action. et al. Helmerhorst EJ. Brady SF. 2004.71(11): H. The antibacterial effects of terpene 7613–7. Spinell DM. Schmid R.48(2):115–25.5(2):111–23. Gunsolley JC. Beta-lactamase producing bacte- nent teeth. Hamilton I. 2004. Some aspects of the Assoc. Iobst SE.27(7):520–5. Wang S. Jack RW. Turnbaugh inflammation. Regulation of ginkgoneolic acid on the growth. 80. Oral Microbiol E. Inoue Y. Gill SR. Griswold AR.96(3):199–207. Burne RA. Validation of an in vitro biofilm model of suprag. Van der Weijden G. Chem Biol. A meta-analysis of six-month studies pooled dental plaque. 1995. Hamashima dissection. Winkel EG. J Dent Res. mode of action of chlorhexidine. J Bacteriol. Herrera D. Bacteriol. 87. Clinical efficacy of antimicrobial 1964. Longworth AR. Burne RA. Singh A. A comparison between Spain and The S. Hay DI. 1998. Gordon J. Bowen WH. elucidation of the antimicrobial repertoire by genetic 97. Shi WY.188(3):834–41.48(11):4121–8.237(2):325–31. Shimada J. J Clin Periodontol. Vorsa N. Seiger M. Burne RA. Koo H. Lamster I. Gunsolley JC. Guggenheim B. sequence analysis of severe caries in young perma. present 76. 2008. In vitro and in vivo bial agents. Jap Dent mutans genome sequence reference strain UA159: Sci Rev. cal evaluation of toothpaste and oral rinse containing resistance? JAppl Microbiol. Nieuw Amerongen A. Hale JD. Slot D. Griswold AR.44(2):331–84. He XS. Van’t Hof W. 1999. regulation and role of the agmatine deim. 2004. J Exp Med. chemistry of unknown soil microbes: a new frontier 35(Suppl):107S–14. Antibacterial 81. et al. gingival 70. Am J Orthod Dentofac Orthop. J-h C. J Clin Microbiol. Hugo WB. Bacterial 16S 93. 99.186(6):1902–4. Chen Y-YM. Leys EJ. Kuftinec M. 2000. Caries Res. J Dent Res.92(Suppl):98S–110. Jameson-Lee M. ternary salts of hexamethylenetetramine I. Hirose K. Duarte S. Handelsman J. some high molecular weight constituents with bacte- yltransferases and Streptococcus mutans acidoge. Ma S. Li F. 1985. and future. Cao Y. Br Dent J. Franco EM. 2006. Rondon MR. Griswold AR. ingival plaque. Hada T. 73. Schüpbach P. Gilbert P. resin monomers based on quaternary ammonium Bacteriocin (mutacin) production by Streptococcus and their benefits in restorative dentistry. Oral microbiology: past. J in vitro. adherence. Xu X. Regulation of gene expression in a bacteria. 96. Johnson J. Int J Oral Sci. Gibbons RJ.178(7):254–8. Rev. Influence of 88.2 Biofilm and Dental Caries 53 68. et al. He J. Netherlands. 1989. 2001. Folia Microbiol. Hall-Stoodley L. 2010. 91. 1916. Gregoire S. Appl Environ Microbiol. Schwartzbaum JA. Janies DA. 1972. and toothpaste compared with some other antimicro. Biochemical effects of fluoride on oral Kolenbrander PE. 84. Metagenomic analysis of the odontic treatment. van Winkelhoff AJ. Allison C. 2013. Samuel BS. Zhou X. and lem of the chemotherapy of experimental bacterial cariogenicity of Streptococcus mutans. Nat Rev Microbiol. Pop M. Biology.78(6):1245–50. The use of sanguinarine in mouthwashes 89. Costerton JW. 2006. Sanz M. Hodgson R. Hayacibara MF. biofilms: from the natural environment to infectious 98. Gill SR.23(5):563–8. Role 85. Deboy RT. 2006. 2007. 312(5778):1355–9. J Dent Res.24(1):79–82. Arch Oral Biol. Stoodley P. for natural products. Caries Res.5(10):R245–9. of antiplaque and antigingivitis agents. Effects 75. histatin-derived basic antimicrobial peptides on oral 77.6(2):103–21. Heng NC. immunology. Firestone ND. The prob- 83. mutans UA159. J Appl Microbiol. acidogenicity. 1990. Distribution.12(8): parameters of gingival inflammation: a systematic 697–704. Biofilms in vitro 86. sanguinaria extract in controlling plaque. Dellemijn-Kippuw N. alcohols on Staphylococcus aureus and their mode of 82. Guggenheim B. Efficacy of Listerine effect of cetylpyridinium chloride‐containing mouth antiseptic in inhibiting the development of plaque rinses as adjuncts to toothbrushing on plaque and and gingivitis. and physiologic significance of the agmatine deimi. Shiraishi A. and sulcular bleeding during orth- PJ. effects of isolated fractions of Brazilian propolis on 74. Izutani N. 1971. Ting YT. of cryptic receptors (cryptitopes) in bacterial Goodman RM. Davis G. Hay DI.

New York: Academic. Park YK. Streptococcus mutans growth and on glucosyltrans.82(5):338–44.40(2):245–8. Mol Microbiol. Qi F. Microbiol Mol Biol Rev. Rosalen PL. 129.100(5): Jorgensen A. Ho CM. regrowth. Koo H.13(2):108–25. Antimicrob Agents Chemother. Adv Dent 112. Jensen ME. Two-year caries clinical 100. J. Jordan HV. ity of green tea flavor components and their combina- edge. Shi W. Shi W. P. J Clin Periodontol. 2005. 2002. Koo H. Montemagno C. 1. 2010. pH homeostasis. Li Y. J Bacteriol. Heydorn A. human isolates. 2013. microbiology. penetrate. Koo H. Interspecies interactions within oral microbial commu- 107. Zhang J. 1971. Barton JA. Qi F. 113. Surface-active quaternary ammo- 266–9. Competition and cetylpyridinium chloride. Matheny JL. Adv Dent Res. 1950. Characterization of Park Y. editor. ISME 46(5):1302–9. 2007. In: Schaechter M. Kreth J. coexistence between Streptococcus mutans and dine mouthrinse formulations for effects on plaque Streptococcus sanguinis in the dental biofilm. He J. 105. tal caries causation: an alternative to Streptococcus 126. Cai L. Mateo LR. 1989. 114.4(3):135–40. Pseudomonas aeruginosa wild type. J Dent Res. the Actinomyces naeslundii ureolysis and its role film accumulation and polysaccharide production by in bacterial aciduricity and capacity to modulate apigenin and tt-farnesol. 304–10. 2008. Molin S. Antimicrobial activ- products in caries research: current (limited) knowl. Kaplan AL. 106. Oral Biol Med. Himejima M. J Jap Soc Food 122. and 110. J in dental biofilms to inhibition of dental caries. Kubo I. et al. He Z. BMC Microbiol.36(6):463–7. Rosalen PL. Hayacibara M. Schobel B. Jeon J-G. Addy M. Stoodley IV pili mutants. Crit Rev from Ceanothus americanus against oral pathogens. catechin to Streptococcus mutans. Kuramitsu HK. Jakubovics NS. flagella and type 125.71(4):653–70. Microbiol Res. J Dent Res. Oral Sci. Streptococcal antago- combination with fluoride on gene expression and nism in oral biofilms: Streptococcus sanguinis and structural organization of Streptococcus mutans in Streptococcus gordonii interference with Streptococcus biofilms. Anderson MH.190(13):4632–40. Antibacterial activity of tea 2003. Klausen M. susceptibility of 40 ex‐situ environmental and 109. Co-ordinated bacterio- to meals and the effects of chewing gum. Leys EJ. Koo H. 2014. J Bacteriol.5 % arginine. J Agric Food Chem. Qi F. Herzberg MC. The road to ruin: study of the efficacy of novel dentifrices containing the formation of disease-associated oral biofilms. Liu YL.20(1):17–21. Phylogenetic and functional gene structure shifts of ferase activity. Biofilm formation by 1132–40. Ellwood R. Liu Y. et al. Paster BJ.18(1):3–5. 1989. Mol Microbiol. nase gene expression and stress tolerance. Hu T.46(1):97–102. ble mechanism for taking up DNA from neighbouring 103. 1960. Denny P.52(5):782–9. Kraivaphan P. Bowen Res. 1. Kawamura J. Oxford. Cury JA. The oral fluid MEMS/NEMS chip (OFMNC): of microbiology.54 X. Zhang Y.190(10): 116. 121. Clinical and microbiological effects of a 131.62(10):617–22. Leid JG. J Bacteriol. Gregoire S. Effects of of experimental dental caries.45(3):243–63.8(9):1879–91. 115. 102. mutans. Jeon JG. Wu CD. 2012. 101. 2009. Burne RA. Kopczyk RA. Abrams H. 3646–57. 2002. Xin et al. Kreth J. Kreth J. New bacterial species disease research. J. Ledder R. Zhou Y. Li X-C.1:304–20. Willis C. Merritt J. Immun. Triratana T. Strategies to enhance the biological effects 130. Influences of naturally occurring agents in 119. Cury J. A comparison of 117. Phytochemistry. Caries Res. Koo H. Merritt J. He X. the oral microbiomes in periodontitis patients. Costerton JW.191(23):7363–6. Kolenbrander PE. Int Periodontol. an insoluble calcium compound and Oral Dis.50(2):236–42. Li Y. of Streptococcus mutans regulate agmatine deimi- 2008.16(8):729–39.21(6):441–4. Xiao J. Human leukocytes adhere to. McBain A. Inhibition of Streptococcus mutans bio.450 ppm fluoride. Arch Oral Biol. diagnostic and translational applications. UK: Elsevier. Effects of compounds found in propolis on 128. 2006. Antimicrobial compounds mutans and the specific-plaque hypothesis. The in vitro effects of amine fluo. Caries Res. Yuan M. 2009. Natural 120. Amornchat C. . Lambertsen L. Ragas P. Encyclopedia et al. Shirtliff ME. Shi W. Lawrence CA. Human plaque pH responses 118. 104. A mixed-bacteria ecological approach respond to Staphylococcus aureus biofilms. rides on plaque bacteria*. 2003. 1994. Kolenbrander PE. Burne RA.167(6):204–8. 1988. Cummins D. 2005. Multiple two-component systems of fluoride on dental biofilms. Jenkins S.48(6):1511–24.9(1):228. Rosalen PL. Br Dent cin production and competence development: a possi- J. Shi W. triclosan and chlorhexi. Brown AT. J Appl Microbiol. Progress toward sanguinaria-containing mouthrinse and dentifrice understanding the contribution of alkali generation with and without fluoride during 6 months of use. et al. 108. Falsetta ML. Wefel JS. Jakubovics NS. 2011. challenges and future perspective. 1991. Actinomyces naeslundii. 111. nities.59(4): 123. Nascimento M. Klein MI. 2008. 2005. associated with chronic periodontitis. Rosalen P. Findings and implica. Bachrach G. 1992. et al. Newcombe R. Griffen AL. Kay H. chronic triclosan exposure upon the antimicrobial tions. 2009. Aaes. WH. Liu Y. Zhou X. Gilbert P. J Periodontol. tion effects. Sci Technol. Lux R. Kumar PS. Xu X. J Bacteriol. nium germicides. J Antimicrob Chemother. Oral 127. Rodent model systems in periodontal Moeschberger ML. Wilson M. 2002. Keyes PH. Takeo T. The infectious and transmissible nature 124. Kleinberg I.161(4): 2003.70(11):6339–45. Infect to understanding the role of the oral bacteria in den. 2006. species.187(21):7193–203.57(2):392–404. 1997. Muroi H.47(6):582–90.

Microbiology of dental plaque biofilms 7‐epiclusianone on glucan synthesis. tim.5(6):358–70. Matsui R. Grossman N.2008. 2012. Earnest R. Triclosan Streptococcus sobrinus and Lactobacillus casei by targets lipid synthesis. de Sousa Cabral TF. Effect of long–term consumption 2011. Comparative effect of SnF2. 1981. Garvan CW. Dental plaque bio. saliva levels of Streptococcus mutans. Plasschaert AJ.36(2):155–60. Gorby YA. 150. Loesche WJ. conflict and control. Savilahti E.18(Spec):9A–14A. 1991. et al. dental decay. O’Toole GA. gordonii: autoinducer 2 controls carbohydrate metabo- vitis plaque formation. 1987. mixed continuous cultures. 2009. 161. McNab R. J Bacteriol. et al. Moter A. Nagaraja HN. The arcABDC gene cluster. Marsh PD.55(1):16–35. Marsh PD. Watson WJ.149(Pt 2):279–94. 2009.56(11):1282–9. ome. 160. Vander 154. Monds RD. Stoneking 149. Arch Oral 144. Oethinger M. Adv Dent Res. 136. Näse L. J Bacteriol. Morou-Bermudez E. McLean JS. M. Future ence. Dental plaque: biological significance of a Biol. doi:10. White Dental 140. 2011. The human mouth as a focus of infec- a cetylpyridinium chloride mouthrinse on gingivitis tion. Multidisciplinary research 157.282(2):174–81. Devine DA. Urease activity in dental plaque and saliva of 143. Caries Methods. Gibb MFG. de Almeida B. sition of experimental salivary pellicles. Kuramitsu HK.1001. Acid tolerance mecha. Mason MR. e77287. acidogenicity and their role in oral health and caries. dren. The developmental model of 141. J Microbiol mutans in germ-free Osborne-Mendel rats. givalis. Establishment and symbiosis of Actinomyces JK. and formed plaque. Lusk SS. 1976. Association of Streptococcus mutants with human 188(23):8095–102. Tang K. Inhibitory effects of 145. Quinque D. 2010. 2009. Periodontology. Co. 142.24(2):89–95. et al. Saxelin M. Caries Res. Tenovuo mutans. Dos 2005. Wong microbial biofilms: ten years of a paradigm up for review. Pönkä films: communities. tance to antimicrobial agents. Elias-Boneta A.2 Biofilm and Dental Caries 55 132. 1998. J Ind Microbiol. Arginine deiminase system and bacterial adapta. Mikx FH. Stalon V. Dent Clin and biofilm formation by Streptococcus mutans. North Am. 164. arginine deiminase pathway of Bacillus lichenifor. Poussa T. Levy SB.108(4):587–92. Loesche WJ. 2010. Infect Immun. Billings RJ.54(3):441–54. GG. Mayhall CW.138(3546):340–2. Burne RA.19(4):636–43. 2006. Witt J.10(2):123–32. Loos PJ. Rowan J. Joshi V. Maltz M. Lumikari M. Hatakka K. Mankodi S. J Bacteriol. Inhibition of the growth of Streptococcus mutans. of a probiotic bacterium.53(1):198–200. Probiotics: do they have a role in oral Wauven C. Streptococcus mutans and Veillonella alcalescens in 137. Epub 2009 Jan 1021.35(6):412–20. specific bacterial signatures in the oral microbiome.17(2):73–87. 2001. 1984. in milk on dental caries and caries risk in chil- Kumar PS. Mayhew R. J Am Soc lism and biofilm formation with Porphyromonas gin- Prev Dent.24(2):133–6.185(1):274–84. 2013. The micro-organisms of the human agenda for novel antimicrobial agents for caries preven. 1890.1016/j. J Dent Res. 2003. Mechanisms of biofilm resis. Cook 135.4(4):31–3. terial arginine and urea catabolism with caries experi- nisms utilized by Streptococcus mutans.60(10):1809–14.394(6693): oral peroxidase systems in human saliva. 159. The carbohydrate compo- 133. relationship with other caries risk factors. El-Sabaeny A. encoding the medicine and dentistry? Eur J Oral Sci.62(3):337–44. Arch Oral 531–2. Majors PD.1011. Moffitt GS. Nature. 2003. Lamont RJ. 1976. Philadelphia: The S. 153. Are dental diseases examples of ecological children during a three-year study period and its catastrophes? Microbiology.180(24):6468–75. J Am Dent 151. Camerlengo T. Am J Dent. tion to acid environments. 113(3):188–96. Nurmio S. and SnCl2 on the growth of Streptococcus 134. J Clin Periodontol. Miller WD. Marquis RE. 162. PLoS One.S. 2001. Straffon LH. Dental plaque as a biofilm. 152. Effects of an oral rinse on experimental gingi. 156. Corpron R. Arch Oral Biol.32(s6):7–15. Appl Environ Microbiol. 163. caused by them. 2005. McMurry LM. et al. A. Nascimento MM. Biol. Meurman JH. Assoc. Yatsuda R. and its activation by the arginine repressor 155. NMR methods for viscosus. and plaque. Bowers GM. Symbiosis of argR. NaF. Konig 138. A. Browngardt CM. 1975. Lactobacillus rhamnosus 147. Salles L. Minard KR. passim.5(3):403–17. Marsh PD. J Oral The effect of chewing xylitol gum on the plaque and Pathol. He T. Marsh PD. Maghnouj A. Nasidze I. O’Toole GA. Butler WT. Li J. Santos MH. Nagem TJ. et al. Genome Res. Barbieri B. 1975. Garcia-Rivas V. Deep sequencing identifies ethnicity. Global diversity in the human salivary microbi- teriocin immunity proteins in the antimicrobial sen. Fredrickson KG. Oral Microbiol Immunol. 2005. J. Correlations of oral bac- 148. 6-month clinical trial to study the effects of 158. Ford SK. Pinchuk GE. Trends Microbiol. Beighton D. sitivity of Streptococcus mutans. Role of bac. van der Hoeven JS. biofilm and community life‐style. Trends Microbiol. 20(7):407–10. 139. 1995.11(6):1252–60. . Mikx FH. Tow HD. Mah TF. R. 1974. Microbiol. 1891. Marsh PD. Bender GR. Burne RA. Res. Bsoul S.15(3):169–75. Soukka T. LuxS-based signaling in Streptococcus WC. Van der Hoeven JS. 2008. Bauroth K. Matsumoto-Nakano M. Miller WD. Cvitkovitch D. 146. 1998. Gordan VV. Bradshaw DJ. Brown L. Murata RM. Streptococcus sanguis and Streptococcus in situ biofilm metabolism studies. FEMS Microbiol Lett. Murray DR.9(1):34–9. mis. Lancet. mouth: the local and general diseases which are tion and treatment.8(10). Brignoni-Nazario V. 2005.

Rapid and quantitative Whitford GM. 1991.1111/j. et al. 2008. J Clin Microbiol.36(2):93–100. 2012. Guggenheim B. .x. Peterson S.184(4):1140–54. Bedi G. Schroeder HE. Enhanced anticaries efficacy of a 2015–21. Mutualism versus independence: 1969. Shani S. Shapiro S. A method of studying 168. in in vivo human acquired enamel pellicle using 175. Guggenheim B. Shu M. 187.22(1):61–6.1399-1302X. Suárez Pérez E. 170. Pessan JP. Koo H. Hewitt J. C. et al. genetic analyses of mutacin III biosynthesis genes.24(3):183–9. Comparison of the cariostatic em rato de ssalivado dessalivado. Purification of mutacin frice: 3-year clinical results. 2009. Bellato CM. 2001. 173. 1999. Infect Immun.87(5):461–5. Helv Odontol Acta. Streptococcus mutans. Chen YY. and salivary composition. Van biotic mutacin I and a nonlantibiotic bacteriocin. Helmerhorst EJ. Hansen MC. Yamamoto 166. Shapiro S. 171.34(3):260–7. 172. Yin W. Crall J. a cariogenic compounds from Japanese green tea. Oral Microbiol Immunol.9(4):202–8.00493. monoclonal antibodies. Appl Environ Microbiol. Garcia L. Zhang W. 2009. Xin et al. Jewett A. An in vitro oral Veillonella species in saliva. Cury J. Steinberg D. Paster BJ. Slot DE.8(5):231. 2001. Kolenbrander PE. adulthood. bacterium.45(2):162–73. Rivera children with chronic renal failure: plaque pH. Qi F. 180. Buzalaf MA. The vary pH. et al. Woodhead J. Minami T. bial activity of essential oils and essential oil compo- Oral Microbiol Immunol. Korwanich N. Pediatr Res.25(6):438–43.85(10): Bacteriol.19(8):796–9. Doherty F. The antimicro- biota on different oral surfaces in healthy children. Fujiwara T. 179.17(4): 2008. 193. Mateo LR.A-074:30 phenols in SPF rats.2008. Hirzel HC. Kolenbrander PE. Kim M. bial mouthrinses. 192. cetyl. Clemente JC. Corley RP.243 % sodium fluoride/10 % xylitol/silica denti- 174. Aggregatibacter 185. Meier A. Caries Res. Morou Bermudez E. produces both the lanti. Matsumoto M. Annu Rev Microbiol. sobrinus and glucosyltransferase in biofilms. Zhang YP. Periasamy S. et al. Genome Res. Sampaio FC. and application. Kuroki T. dental plaque morphology. munities in twins from early adolescence to early 56:117–37.53(9):2307–11. Caries resistance in 188. in a longitudinal survey of salivary bacterial com- ogy. The role of sucrose in cariogenic dental biofilm tiple phenotypes during development as a biofilm. 2002. Makimura M. 1995.6(6):2152–60. elderly patients.13(1):22–7. Caries Res. III from group III Streptococcus mutans UA787 and 190. Mamai-Homata E. 1997. Lauris JR. Agric Biol Chem. 878–87. Egland PG. Haffajee AD. Riley MA. J Dent. Knights D. J Proteome Res. relationship between dental caries status and dental 1985. 1998. Stewart B.22(11):2146–52. Stahringer SS. J Dent Res. cacy of a dentifrice containing 1. Moran J.32(1):75–80. T. M. Oppenheim FG. Van Loveren C. triclosan. Palmer Jr RJ. Quirynen Res. Walters WA. 1994. Fluoride uptake by detection of Streptococcus mutans with species-specific plaque from water and from dentifrice. Efeito da propólis Sobue S. Sintes J. 2002. Ooshima T. et al.41 Suppl 2:S29–34. Kazmerzak K. Friedman M.67(5):486–9. 365–71. Camper AK. The action of thymol on oral actinomycetemcomitans builds mutualistic biofilm bacteria. UA140. 1995. Ehrlich GD. 1989. 2007. Bacteriocins: evolution. communities with Fusobacterium nucleatum and 186. A comparison of chlorhexidine. Palenstein Helderman WH. Gizani S. 2000. The group I strain of LC-ESI-MS/MS. Am J Dent. The effect of chlorhexidine varnish on root caries: a 176. Willumsen T. Rosalen P. ecol. 2007. biofilm model for comparing the efficacy of antimicro- 77(9):3542–51. Infect genic effect of amine fluorides on Streptococcus Immun. Caufield PW. 1450 ppm fluoride to a dentifrice containing 1450 ppm 177. The anticario- using saliva as the sole nutrient source. 167. 2006. 2002. Caries 169. 2013. plaque urease activity. Silva SM. Palmer Jr RJ. Srisilapanan P. Rickard AH. Blehert DS. Comparison of the effi- rinse products for plaque inhibition. Chen P. Anticaries effects of polyphenolic extract against Streptococcus mutans. Cury Davies DG. and C31G mouth. Van der Weijden GA. Giertsen E. 165. systematic review. Hybridoma. Nishihara Y. Newcombe R. 1998. Shapiro S. 181. 2006. Park Y. Wertz JE. 2011. Paes Leme AF. 60(6):1446–56. J formation – new insight. Siqueira WL. The micro. Caufield PW. Miranda C. Oral Microbiol Immunol. cin IV. Koo H. Otake S. Papaioannou W. Oral Microbiol Immunol. Caries Res. Renton-Harper P. Chen P. Shi W.67(1):15–21. Sakanaka S. muta. Nurture trumps nature 178. Campagna fluoride alone in the management of early coronal car- SR. Sauer K. Semmelhack MF. J Periodontol.69(9):5794–804. 191. Hamada S. Guggenheim B. 15a Reunião Anual effects between regimens to administer oolong tea poly. Caries Res. Chuensuwonkul pyridinium chloride. doi:10. Olsen I. Costerton JW. Pseudomonas aeruginosa displays mul- JA. strategies of mixed-species oral biofilms in vitro 183. Identification of protein components Appl Environ Microbiol. J Dent Res.56 X. nents towards oral bacteria. Autoinducer ies as assessed using Quantitative Light-induced 2: a concentration-dependent signal for mutualistic Fluorescence. Aas JA. sali. bacterial biofilm growth. Papagiannoulis L. Preza D. Browngardt CM.10(4):241–6. 184. Taniguchi M. Qi F.46(6): Volpe A. Hume WR. da SBPqO Res. Vaandrager NC. Grinde B. Escalante C. 0. Antibacterial substances in Japanese green tea Hirasawa M.5 % arginine and 1996. Addy M. Bacterial profiles of root caries in 189. Mol Microbiol. Gygi SP.65(9):3880–7. McCool J. 182.

Vaidyanathan M. Huntington E.9(7). 1988. Trahan L. Cheng CY. Gan formation and on gingivitis. cance. Costerton odontitis. Oral Microbiol Immunol. Antibacterial and antiplaque effects of a novel. Wang R. Formulation and tions in human parotid saliva with caries experience. Penicillin- bacteria in biofilms. Weiger R. biochemical composition of both free smooth surface 2006. 1993. Wilson CO. Antibiotic resistance of 213. 2005. 2005. Wang BY. tions on hard and soft enamel.2:71. Gibb R. Harris NO. J Dent Res. Gilbert S. Dunavent J.18(1):3–10. Suddick RP. leukemia pediatric hosts from healthy populations. 2007. riocin production by Streptococcus gordonii. van der Velden U. 204. J Dent. Davies DG. 2005. Heavy metal resistance of rial and antiadhesive effects of mouthrinses in vivo. D. 2009. Bsoul S. On structural changes in human 202. Fraser-Liggett a 24-hour retrospective dietary history of sugar intake CM. Turnbaugh PJ. Brecx Food Sci Technol Bull. Holgerson PL. 222. e102116. Kent RL. Bevacqua film model. Annu Rev Microbiol. health effects in children. 225. gingivitis mouthrinses. The human microbiome in adolescents. Dent Cosmos.14(7):2535–54. Int Dent J. 2001. inal and pharmaceutical chemistry.24(8):538–43. The need for antibacterial approaches enamel. Xylitol: a review of its action on mutans 220. 200. Qi F. Microbiological effects of mouthrinses ties. Robinson C. 2009. formation. Vu B. Xu X. Witt J. gation of mutans streptococci. 21(1):8–12. and aggre- 210. Walters P. Flood J. Tsang P. ten Cate JM. et al. Kuramitsu HK. et al. An approach to differentiate between antibacte- 201. J Contemp Dent Pract. Devine D. Ling L.449(7164):804–10. 215. growth. 218. Wang Y. Oralprophylaxe Kinderzahnheilkunde.28(2):188–91. J Dent Res. extracted from Galla chinensis in a multispecies bio- 211.2(3):129–31.18(Spec): 208. Lippincott. Ashley FP. 219. Wester-Ebbinghaus T. Dental plaque pH recovery effect of arginine 43(4 Suppl 1):441. agents determined using in vitro and ex vivo meth. discussion 192–188.57(4):680–4. Du Q. Sadxton C. Ivanova EP. Comparative clinical trial of two anti- 2009. Ramji N. Barendregt D. J Clin Periodontol. Wang B. Ley RE. Chen M. Xie Q. characterization of a novel fluoride-releasing dental J Dent Res. alcohol-free oral rinse with cetylpyridinium chlo- 2008. with special reference to clinical observa- to improve caries control. D. 1998. Gordon JI. Burgess JO. Gallotannins inhibit ods. 459–65. 197. Parsek MR. Triclosan on supragingival plaque and calculus 216. Stephan RM. Dellemijn-Kippuw N. Winkel EG. Gibb R. hood caries before and after therapy. 226. 1995. Hamady M. 217. Wood S. Metcalf D.6(1):1–9. JW.74(2):686–90. Adv Dent Res.23(6): D. 2009. Association of free arginine and lysine concentra. Kanasi E. Crawford RJ. Gisvold O. King CJ. 2003. agement. water-insoluble glucan synthesis. Cummins D. Int Dent J.90(11):1298–305. Lancet. Taylor PW. Nature. Barnes 206. Wilson RF. 199. 1988. Microbiota of severe early child. Pediatr Dent. Wang XL. 195.24(3):203–10. Yang X. Am J Dent. Zhou X. Stecksén‐Blicks C. Beighton photodynamic therapy of oral plaque biofilms. Appl Environ Microbiol. Interactions between oral 1990. J Dent Res. Crit Rev Oral Biol Med. 2002. bicarbonate rinse in vivo. Putt M. J Clin Periodontol. Low SB. and approximal plaque and salivary composition and 205. You M. Sheehy E.56:187–209. 2008.45(1 Suppl 1):77. Zhou X. extracellular polysaccharides involved in biofilm 1944. degrading enzymes in sites associated with adult peri- 196.2 Biofilm and Dental Caries 57 194. Twetman S. Molecules. Shi W. 1983. Peng D. Billings RJ. Witt J. composite.23(4):257–66. acidogenic oral bacteria. J Dent Res. Textbook of organic medic- streptococci and dental plaque–its clinical signifi. Stijne A. 67(1):51–5. Oral microbiota distinguishes acute lymphoblastic 2011. not the lesion. 203. 2006. The role of xylitol in patient caries man. 1954. YH. Caries Res. Chen C.62(8):882–4. 223. 2005. Antimicrobial properties of dentine bonding J Antimicrob Chemother. ride. Sauer K. bacteria: inhibition of Streptococcus mutans bacte- 198. Loo 15(2):115. Historical perspectives of 15(8):499–505. containing antimicrobials. Trahan L. 2014. Effect of xylitol on the growth and glycolysis of 224. Probiotics and oral J. oral biology: a series.37(7):514–21. Mouton C. Perinpanayagam H. 214. M. Williams JL. 207. Costerton JW. Walker CB. Hughes CV. Twetman S. CY. et al. Antimicrobial properties of green tea catechins. Biofilms as complex differentiated communi. Raubertas RE. 227. Anticaries effect of compounds odontitis. Stapleton PD. Medical approach to dental 221. Dent Mater. Stewart PS. beta-Lactamase producing bacteria in adult peri. Xue J. PLoS One. Knight R. 1997.69(4):2313–20. Wu R. Bowen WH.43(7):559–65. 2012. 1995. Netuschil L. Wu-Yuan C. Oral Microbiol Immunol. Intra-oral hydrogen-ion concentrations 212. VanWuyckhuyse BC. 40:505. Tanner A.31:122–7.22(11):1014–23. . 2006. van Winkelhoff AJ. Hamilton-Miller JM.71(1):354–62. Appl The effects of three silica dentifrices containing Environ Microbiol. biofilm and planktonic Pseudomonas aeruginosa. 1987.1(2):135–51. Arch Oral Biol.358(9276):135–8. Mayrand 15A–17A. Tyler KZ. 1898. Erythrosine is a potential photosensitizer for the 209. 1990. Dunavent J. Teitzel GM. Vadeboncoeur C. Chin J Dent Res. Svatun B. Li J. project. Stoodley P. 2nd ed. Walker CB. Relationships between the caries: fight the disease. Bacterial associated with dental caries activity. Int J Paediatr Dent. Philadelphia.

180(16):4154–9. Gao H. Scheie AA. Lo CC. 233. 234. The tea catechin epigallo. Melo MA. Microb tion within oral biofilm. Involvement of gshAB in the interspecies competi- crobial resistance in bacteria: an overview. Zhou X. Zagorec M. 236. 819–24. Pérez-Martínez G.58 X.55(3):1229–36. 229. et al. Weir MD. Structural and functional analysis catechin gallate suppresses cariogenic virulence of the gene cluster encoding the enzymes of the argi- factors of Streptococcus mutans.89(11):1304–8. Xu X. Xu echin gallate inhibits Streptococcus mutans biofilm HH. Saliva microbiomes distinguish caries-active from new monomer dimethylaminododecyl methacrylate. Li X. Xu X. Zhang K. Ning K. 230.15(5):R66. J Dent. Høiby EA. Hu DY. Zhang K. Zhang YP. Li M. Bai Y. Wu EJ. J Dent Res. Fan X. 239.6(1):1–10. nanoparticle-containing adhesives on dentin bond 2012. healthy human populations. Xu microbial communities. Heir E. 1998. Liu C. and anti-biofilm activity of bonding agent containing et al. Dent 231. Cheng L. Yin W. Liu KL. Martin JC. Mater. Zheng X. Zhang K. Wang W. Zhou Y. J Bacteriol. et al. Xu X. Wu CD. Exploration of bacterial ing 1. J Dent Res. Xin et al. 2014. Cheng L. ISME J. Weir MD. HH. Chemother. Effect of quaternary ammonium and silver formation by suppressing gtf genes. 2012. et al. The anti-caries efficacy of a dentifrice contain. Mihindukulasuriya KA. Zhou XD. 2012. Zhou XD. et al. B-T. Oral cavity contains distinct niches with dynamic 237. Xue J. monofluorophosphate assessed using Quantitative Genome Biol. Zhang K.92(9): Drug Resist. Lunestad 238. 2011. Wu CD. Effect of water-aging on dentin bond strength 232. Environ Microbiol. He J. Li K. Wang Y. Bai Y. Antimicrob Agents nine deiminase pathway of Lactobacillus sake.28(8):842–52. Tea catechin EGCg sup.57(6):678–83. Zúñiga M. et al. 228. Wylie KM. Zeng X. Yazdankhah SP. 2013. 2013. Yang F. Champomier-Verges M. Triclosan and antimi. 2013. Li Y. Tea catechin epigallocat. Xu X.12(2):83–90. J Dent. strength and dental plaque microcosm biofilms. 235. Suppl 2:S22–8. Light-induced Fluorescence (QLF).41 presses the mgl gene associated with halitosis. Arch Oral Biol. La Rosa PS.5 % arginine and 1450 ppm fluoride as sodium community classes in major human habitats. 2006. Zhou XD. Fotland TØ. Wu CD. . 2014. 2010. Pretty IA.

nitrogenous products like urea and ammonia. The average concen- Sichuan University. also called acini. People’s Republic of China tration and function of saliva composition is e-mail: wangrenke323@163.com shown in Table 3. food glands produce watery saliva with high content of debris. About 90 % of the total secretory endpieces. glucose. tides. Saliva and Dental Caries 3 Wang Renke 3. they produce watery saliva with high con- tent of enzymes like amylase and lipase. Xuedong (ed. In normal physiological condi. and buccal and labial mucosa which produce only a small percentage The normal salivary pH is slightly acidic. immunoglobu- W. A variety of proteins are also found in saliva such as enzymes. There are also a number of minor salivary glands situ. © Springer-Verlag Berlin Heidelberg 2016 59 Z. traces of albumin.1. but pH in salivary flow can range from 5. other antimicrobial factors. Chengdu. 6–7. major salivary glands – the parotid glands. palate. glycoproteins.). mucin-rich fluids. potassium. And the secretions Whole saliva is mainly the mixture of secretion of submandibular glands are a mixture of mucous of salivary glands.2 Salivary Composition ated on the tongue. the parotid vicular fluid. mucosal Department of Operative Dentistry and Endodontics. It also contains gingival cre. and sublingual glands. and phosphate. magnesium.1. sub- mandibular glands.8 (peak flow). while 3. Upon stimulation. bicarbonate. and human cells including leucocytes and enzymes like amylase and lipase. nonadherent microorganisms. The different epithelial cells.5 L [1]. and macromol- ecules. and serous fluids. Dental Caries: Principles and Management. the average daily flow of whole saliva is determined by their different composition of the between 1 and 1. mucins. 3. some polypep- West China School of Stomatology. Salivary electrolytes include sodium.1007/978-3-662-47450-1_3 . Salivary fluid con- the total volume of salivary proteins is secreted sists of approximately 99 % water and 1 % sol- by them. about of saliva.1.1 Formation of Saliva-Salivary the secretions of sublingual glands are predomi- Glands and Secretion nantly mucous. Salivary volume of saliva is secreted by the three paired gland fluid is produced by acini [2]. calcium. utes.1 Salivary Flow The parotids are serous glands. properties of the secretions of these glands are tions. including electrolytes. upon stimula- and Composition tion. Renke lins. the function of the minor sali.3 vary glands is also important since about 70 % of (low flow) to 7. and oligopeptides [3]. However. DOI 10. as same as of those minor salivary glands.

antibacterial action Lysozyme 0. buffering Uric acid 0. modulate demineralization and remineralization.00 h [2].2–0.2 g/L Antibacterial action IgG 14 mg/L Antibacterial action IgM 2 mg/L Antibacterial action Lipid 20–30 mg/L 3. The salivary flow and composition dition.11–0. The salivary flow rate usually increases dur- flow rate is 1. cussed later). while stimulated whole saliva [4]. water balance of than 0.1–2 mM Antibacterial action Organic Urea 2–6 mM Modulate pH.60 W. buffering. attach to microorganism. vary flow rate. Renke Table 3. dental plaque metabolism.5 mM Na+ 6–26 mM K2+ 14–32 mM NH4+ 1–7 mM H2PO4− & HPO42− 2–23 mM Modulate pH. antibacterial action Glycoprotein sugars 0.1 The average concentration and function of saliva composition Composition Concentration Function Inorganic Ca2+ 1–2 mM Modulate demineralization and remineralization Mg2+ 0. including the nature and duration vary flow rate.0 ml/min and both of them have ing the day and reaches the acrophase in the late wide ranges.5 ml/min.2 mM Indication for kidney function Amino acids (free) 1–2 mM Glucose (free) 50 μM Lactate 0.38 g/L Digestion. modulate demineralization and remineralization Cl− 17–29 mM HCO3− 2–30 mM Modulate pH. It’s almost . aggregate.1 mL/min for unstimulated saliva and the body.5–5 μM Modulate demineralization and remineralization. aggregate. In normal con. buffering F− 0. the unstimulated whole saliva flow rate is of saliva display large variations during the day 0. cleanse.4–2 g/L Lubricant. around 15.5–2. afternoon. the emotional state.00–17.2 mL/min for stimulated saliva.3 g/L Cleanse.3 Salivary Flow Rate The secretion of salivary glands is mainly con- and Influence Factors trolled by parasympathetic impulses from the salivary nuclei.3–0.1 mM Fatty acids 10 mg/L Macromolecules Proteins 1. and medication (which will be dis- 0. antibacterial action SN− 0. attach to microorganism. The acceptable flow rate is no less of stimulus.1.11 g/L Antibacterial action Peroxidase 3 mg/L Antibacterial action IgA 0. Several factors influence the sali- There is a broad normal range in individual sali. dental plaque metabolism Amylase 0.

and peptide hormones. the plaque pH returns slowly to the start- buffer mainly takes place in buffering below pH ing level over 30–60 min. because of the powerful salivary bohydrates. respectively [5]. This rhythm could be related to change of hormone level during the day and indicates the importance of taking oral hygiene procedures before going to sleep. causing a drop estrogens.1 Salivary Influences driven to be converted into carbon dioxide and on Plaque PH water. two impor- from certain cells. leading to the reduction of pH ph of plaque 2–2. So during intake. Concerning about caries. Following exposure to fermentable car- However. risk of dental caries. change over time is known as the Stephan bonic acid/bicarbonate and the phosphate buffer curve. 3. if there is saliva much remaining food and dental plaque in the oral cavity. increases with flow rate and reaches 60 mM in ence salivary composition by increasing exocytosis stimulated saliva. on Plaque PH and Oral With the presence of carbonic anhydrase VI Microflora secreted by the serous acinar cells in parotid and submandibular glands.6 is called a “critical value” which is intake. the pH at which the tissues start to dissolve and cient concentrations of phosphate in saliva. The resting plaque pH refers to the organic acids. This plaque pH 5. the pH of saliva Acid-producing bacteria. 3. but it Sympathetic impulses are more likely to influ. HPO42−. like Streptococcus may not be as important as the pH of dental mutans and Lactobacillus sp.3 Saliva and Dental Caries 61 zero during sleep. in pH. .3 and pH 7. Unless there is systems in saliva: the carbonic acid/bicarbonate. With the Fig. The The buffering capacity of saliva affects not phosphate buffer plays an important role in only the rate at which the plaque pH decreases unstimulated saliva.. In resting saliva. The protein drates. existed in normal plaque. and the protein buffer. Salivary composition may also tant events happen: (1) bacteria ferment carbohy- be influenced by hormones such as androgens. and 7. The pH a primary phosphate ion H2PO4−. while the optimal buffering range for the car. there would be a great chance for den- tal caries to happen.1 The carbonic acid/bicarbonate equilibrium in absence of protective effects of saliva. finally leading to an increased secreted within the ducts and. additional ingestion of fermentable carbohy- the phosphate. dietary carbohydrates and is usually between 6 tion of hard tissue of teeth. its effectiveness is limited due to insuffi. occurs at pH 6. the plaque pH decreases rapidly buffering capacity. carbonic acid is further 3.2. There are three major buffer after approximately 5–20 min.2 Salivary Influences shifts to the left to produce more carbonic acid. dental caries is not likely to during the first 5 min and reaches a minimum happen all the time. Bicarbonate is below critical pH. glucocorticoids. could bind a hydrogen ion and form how long the pH stays at that minimum. Low buffering capacity The carbonic acid/bicarbonate buffer is the of saliva leads to increased rate of plaque pH fall most important buffering system in saliva during after carbohydrate intake and prolonged time food intake and mastication. and (2) the increased salivary flow rate leads to an increased HCO3− concentration. cause demineralization. These bacteria metabolize fermentable ders and salivary buffering capacity affected carbohydrates in food and produce variety of plaque pH. The carbonic acid/bicarbonate equilibrium (Fig. The secondary phosphate but also the minimum value of plaque pH and ion.2.5 h after the last intake of value in dental plaque and causing demineraliza. Both fermentable carbohydrate remain- oral flora. During food value of 5. HCO3− concentration is as low as 1–2 mM. drates and produce organic acrid.1) 3.

The concentration of IgG decreases to series of studies confirmed an obvious and sus. saliva. SIgA late the microorganism adhesion. Both sugar-containing IgG mainly comes from gingival crevicular fluid. in polymorphonuclear leucocytes. IgM) and non-immunologic factors dases: human salivary lactoperoxidase (HS-LPO). mainly produced by plasma cells located chitin may play a role in the protection against in minor mucous glands. Lysozyme. There are two can prevent bacteria forming colonies or attach. mucins. A nal origin. Due to the external lipopolysaccharide influence on oral microflora. At this time. hence. presence of a series of immunologic (secretory There are two categories of salivary peroxi- IgA. and myeloperoxidase (MPO) formed bacteriocidic activity. SIgA is non-detectable yeast. SIgA against streptococcus mutans but have different bacterial adherence ability.2 Salivary Influences on Oral cleavage of beta-1. (enzymes. also termed sialoperoxidase. Salivary lysozyme. and enzymes produced by bacteria. high-molecular-weight MG1 (>1000 kDa) and or activate complements or provide synergism single-glycosylated peptide chain. while immunoglobulins. It is one of the most important nonspecific defense substances in saliva. and histatins exhibit bacteriostatic. Lysozyme catalyzes 3. but sugar. and sugar-free gum have such effect.2. It is also enhance biofilm formation. MG2 promotes the aggregation . and the quantity increases with the length of pellicle formation. It can neutralize pathogenic viruses. Renke Salivary stimulation after food intake also exposure. vary glands. the flow in less quantity in saliva. Saliva provides a layer. IgM. olism [7]. synthesized in sali- lactoferrin. non-detectable after a few months after birth and tained rise in plaque pH when gum was chewed appears again after tooth eruption. peptides. It’s also able to weight MG2 (200–300 kDa).4 glycosidic bonds between Microflora muramic acid and N-acetylglucosamine residues in peptidoglycan. glycoproteins. and salivary agglutinin play a role in the oxidases have enzymatic activity and are able to oral clearance of bacteria by interfering with catalyze the oxidation of salivary thiocyanate and receptors on the microbial cell wall. and secretory IgA (SIgA) form the specific Salivary chitinase secreted by salivary glands defense system in saliva against bacteria. IgG is the only detect- of saliva increases from a resting value of 0. proteins.5 ml/min to approximately 5–6 ml/min. IgG. and minerals cidic effect of lysozyme related to activation of can stimulate the growth of oral microflora and bacterial autolysins is reported as well. originating from sera. Lysozyme is a cationic protein with low molec- Chewing other material that could stimulate sali. genetically distinct mucin groups: highly glycosyl- ing or penetrating host tissues. low-molecular- with innate defense mechanisms. ular weight from the basal cells of striated ducts in vary secretion such as parafilm also works. ated. parotid glands as well as monocytes and macro- phages. When gum is chewed. IgA. Gram-negative bacteria are more resistant to nutritious source for oral microflora. peptides). nonenzymatic bacteri- proteins. MG1 can be detected in children at the age of 3 years binds tightly to tooth surface and takes part in enamel old. Other immunologic components occur affects plaque pH. Furthermore. kill them directly. Chitin the most abundant immunologic component in is a cellular wall compound of yeast cells. hypothiocyanous acid. The two groups of aggregate or clump bacteria. dibular and sublingual glands that selectively modu- toxins. inhibiting bacterial metab- The immunoglobulins including IgG. saliva has profound cell wall. Salivary per- mucins. free gum displays a more powerful effect [6].4– able Ig in saliva of neonates and is mainly mater- 0. in neonates but become readily detectable 1 week Mucins are glycoproteins secreted from subman- after birth. SIgA is catalyzes the hydrolytic cleavage of chitin. On the other hand. documented that this enzyme functions to aggre- saliva displays antimicrobial activities with the gate bacteria and inhibit bacterial adherence. after sugar consumption. hence it hydrolyzes bacterial Besides affecting plaque pH.62 W. promoting oral mucins display similar carbohydrate chain makeup clearance.

rate and composition. At least 12 sive intake of medication and/or the degeneration histatin-like peptides are identified in human and reduced volume of acini.1 Etiology of Xerostomia individuals [8]. saliva has a protective function in tion therapy of tumors in the region of the head maintaining oral health and microbial ecological and neck. some drugs that may cause xerostomia. Xerostomia.3–0. is referred to the subjective symptom coprotein aggregate cells in suspension that can of oral dryness. about 1. arginine. 14]. A lot of drugs have influence on salivary flow They are implicated in pellicle formation. 12]. The parotid gland is the most radiosen- balance by inhibiting pathogens and regulating sitive gland and then the submandibular gland. while that of stimulated saliva is surface. It is a member of a trans. but not be found in parotid and submandibular saliva. mia may be termed xerogenic. isms and supports their growth. including medication for ization of lipopolysaccharides of the external hypertension. anti-inflammatory. and allergies. might effect. Over 500 membranes of Gram-negative bacteria. Salivary agglutinin (SAG) is a high-molecular. neutral. A medication which is known to cause xerosto- ing metalloproteins and cysteine proteinases. ered hypofunction [13. keeps increasing.2 shows the saliva. vary glands and the minor salivary glands. including 3. As mentioned above.5 ml/min. tion and a significant reduction of unstimulated It could bind to hydroxyapatite and is a compo. Table 3. It’s reported that MG2 pre. radiotherapy in the head and including streptococcus mutans by iron-depriving neck area. while the level of MG1 is higher in caries-susceptible 3. and Its Management dominates in saliva of caries-resistant individuals. flow rate is below 0. resulting rate is below 0. syndrome. also termed dry mouth or dry mouth weight (approximately 340 kDa).3 Saliva and Dental Caries 63 and clearance of oral bacteria. the use of certain drugs. On the other Xerostomia is a common side effect of radia- hand. etc. and inhibition of proteinases includ.3.1 ml/min or stimulated flow Furthermore. nutrients is termed nutritional immunity. Table 3. chelation medications produce xerostomia as a side effect. then the sublingual gland.5 ml/min. Any ferring family and able to link to ferric iron in factors that could influence salivary gland func- saliva and lead to bactericidal or bacteriostatic tion. It would be considered as SAG binds to streptococci surface receptor hypofunction of salivary glands if unstimulated antigen I/II in a calcium-dependent manner. SAG also binds to SIgA. and immunomodula. which is frequently. As life expectancy in developed countries antiviral. It’s causing xerostomia. stomia. Besides iatrogenic factors. including diseases of salivary glands. 10].. depression. some strains of Streptococcus mutans and yeasts. salivary secretion. a 50 % reduction of indi- which promotes clearance of microorganisms vidual salivary flow rate would also be consid- from the oral cavity [9. and the minor salivary . increasingly common in the result of an increased Histatins are a family of peptides rich in histi. reported that lactoferrin is a multifunctional pro. This process of starving bacteria of vital lead to the reduced output of salivary secretion.0 ml/min. effects on bacteria requiring iron for metabolism Sjögren’s syndrome. mucin-like gly. fungicidal. and lysine residues. associated with salivary gland hypofunc- SAG is highly glycosylated and extremely sticky. xerostomia is becoming tory properties [11. Histatins have antimicrobial activity against common causes of xerostomia. always. Lactoferrin is a glycoprotein with a molecular Saliva is secreted by three pairs of major sali- weight of about 80 kDa. pH in oral environment. As there is a wide range in synergistic effect of bacterial aggregation of salivary flow rate.3 Xerostomia Streptococcus mutans.5–2. of metal ions. incidence of systemic diseases and a more exten- dine. bactericidic. aging could be another important cause for xero- tein having bacteriostatic.3 lists Saliva provides nutrients to oral microorgan. the nor- nent of the enamel pellicle and may be involved mal flow rate of unstimulated saliva is about in the initial adherence of bacteria to the enamel 0.

For elderly. a series Antineoplastics Cytotoxic drugs. chlorhexidine). antisterone Antiasthmatic Ephedrine Anxiolytics Benzodiazepines 3.. fluoxetine. daily use of topical a dose of 60–70 Gy would cause a rapid reduc. It’s reported that 25 % of general population Rare causes Amyloidosis Hemochromatosis complain of xerostomia or symptoms associated Wegner’s disease with it.2 Common causes of xerostomia vary flow almost reduces to zero and hardly Class Cause recovers completely after the treatment.3. dothiepin One of the most important functions of saliva Antihistamines Diphenhydramine. including Chronic graft-versus-host disease thyroid dysfunction. mucosal trauma and ulceration. propranolol and phosphate.3 Medications associated with xerostomia tion. These disor- HIV disease ders influence the salivary flow either through HCV infection pathophysiological process or the medical treat- Primary biliary cirrhosis ment of the disease. By 5 weeks of the treatment.2). eralization and virtually lead to dental caries didanosine (Fig.05 %). hyoscine cussed in a review [15]. and placement of sealants. [15] ence different extent of dysarthria. a single dose above 52 Gy observe a variety of caries preventive procedures. and effective carbohydrate Opioids Meperidine clearance. As the quantity of saliva secretion reduced Others reversibly or irreversibly. prazosin. dysphagia. Cystic fibrosis Xerostomia is a common condition in popula- Diabetes mellitus tion. the influence without ectodermal dysplasia) of xerostomia in life quality brings to great atten- Triple A syndrome tion. atenolol. bupropion. patients could experi- Cited from Porter et al. lithium. As salivary output decreases. so con. The clinical consequences Class Generic name and management had been comprehensively dis- Anticonvulsants Atropine. candida infec- Table 3. post-traumatic stress salivary glands Sarcoidosis disorders. and dental caries. Diuretics Chlorothiazide. furosemide. plaque con- ventional radiation treatment of oral carcinoma at trol. cimetidine protecting against demineralization and replen- Antihypertensives Terazosin. Iatrogenic Drugs Besides the factors mentioned above. the sali. anxiety. the incidence is as high as Salivary gland agenesis (with or 40 %. its management [15]. antimicrobial mouse rinses tion of salivary flow rate during the first week of (e.g. depression. sys- Diseases of Sjögren’s syndrome temic lupus erythematosus. Renke Table 3. of respondents take place with the outcome of interleukin-2 increased demineralization and decreased remin- Anti-HIV drugs Protease inhibitors. The most important one is to reduce the intake of . could lead to severe salivary dysfunction. Antireflux drugs Omeprazole antibacterial activity. ishing tooth surface minerals including calcium clonidine.64 W. It also provides buffering activity. With such a high incidence. 3. retinoids.2 Management of Xerostomia Xerostomia patients should be instructed to gland. is to develop dental pellicle on enamel surface. here we will mainly Antipsychotics Phenothiazine focus on dental caries related to xerostomia and Antidepressants Amitriptyline. Parkinson’s disease. low sugar dietary advice. including oral hygiene instruction. As reported. there are Local radiation a number of additional disorders that may con- Chemotherapy tribute to the presence of xerostomia. treatment. etc. fluoride (0.

and are a part of treatment planning. protective factors including fluoride. and buffering capacity. Lycasin.6) [19]. kind of progressive disease unless intervened sur- saccharin. fermentable to dental caries since acid causing demineraliza- carbohydrates. dental caries. Sugar intake should be confined to meals. ceptibility at the individual level.3 Saliva and Dental Caries 65 Fig. related microorganisms in saliva including tive new strategy against dental caries in xerosto. socio- varnish applied every 3 months is helpful in den. sorbitol. and gel.4. It provides calcium and phosphate (Tables 3.5 and 3. In healthy individuals. Since . these tests are derived from the forms like foam. toothpaste. and host factors including saliva tion is mainly produced by plaque bacteria. gically. which could not be fer. increasing the risk of Dental caries is a multifactorial infectious dis. 3. severity of past and current caries experience. have been developed as indicators of caries sus- should be used to reduce sugar consumption [16]. But in condi- tions of biological or environmental change such as increased frequency of carbohydrate intake or 3. Fluoride is also available in other Generally. varnish. There are more than 700 species of microorgan- Applying to the tooth surface. relatively small amount in saliva. They can be Xerostomia patients should be recommended used to estimate the probability of caries inci- to brush teeth twice a day with a soft bristle tooth dence. measurement of saliva flow rate tal caries inhibition in xerostomia population [17]. and sucralose. and estimation of caries- The use of remineralization products is a rela. high fluorinated vention. rinse. economic status. ions that are lacking because of reduced salivary output. These products usually contain different types of calcium and phosphate compound with 3. the etiological balance of oral Assessment microflora will shift to favor the aciduric bacteria and acidogenic bacteria. behav- rinses and toothpaste accompanied with fluoride ioral and physical factors. aspartame. aiding in remineralization. Streptococcus mutans and Lactobacilli mia patients. ommended by ADA that the daily use of fluoride diet. determine the need for therapeutic inter- brush along with low abrasive. Non-cariogenic sugar substitutes since dental caries is generally considered as a including xylitol.1 Caries-Associated Bacteria or without additional fluoride in the form of paste or medication carrier (products without fluoride). To estimate the caries risk before disease and there should be no sugar consumption has been given more attention in recent years between meals.4 Saliva and Caries Risk poor oral hygiene.2 The chain reaction of reduced salivary flow rate sugars. status. ease that is associated with complex interactions Plaque bacterial composition is most related among acid-producing bacteria. 3. Several caries risk assessment methods mented by acidogenic bacteria into organic acids. medical factors. and attract calcium and phosphate ions to the caries-associated bacteria are usually present in tooth surface. they can provide isms inhabit the oral cavity. It is rec.4.

Recently. or mental disabilities that prevent or limit performance of adequate oral health care by themselves or caregivers) Clinical conditions I Visual or radiographically evident No new carious Carious lesions or restorations/cavitated carious lesions or restorations in last lesions restorations in last 24 months 24 months II Non-cavitated (incipient) carious No new lesions in New lesions in last lesions last 24 months 24 months III Teeth missing due to caries No Yes IV Visible plaque No Yes V Dental/orthodontic appliances No Yes present ( fixed or removable) VI Salivary flow Visually adequate Visually Inadequate plaque bacteria can be released into saliva. 16S rRNA in dental caries. medical. or SCHIP) IV Caries experience of mother. carbonated or non. convenient for dental practitioners. It is reported that high level of sali. No carious lesions in Carious lesions in last Carious lesions in caregiver. and T-RFLP have been utilized vary Streptococcus mutans (>105 CFU/ml) is asso.66 W. for dental caries microbial analysis. cul- Streptococcus mutans and Lactobacilli have ture-independent technologies including checker- been implicated as important contributory species board DNA-DNA hybridization. and culture-independent meth- amount of mutans streptococci [25]. medical syrups) time III Eligible for government programs No Yes (WIC. it is of Lactobacilli (>106 CFU/ml) [26] could be an documented that the level of certain species of indicator for increased frequency of carbohydrate bacteria in saliva can reflect their level in dental consumption [27] and caries progression [28]. sequence analysis. Although the amount of lactobacilli is less scale but definitely suggest new possibilities for sensitive in predicting caries incidence than the fast. physical. Head Start. mealtimes between meal with anytime other carbonated soft drinks. plaque. supplements. 21].4 ADA caries risk assessment form for age 0–6 Low risk Moderate risk High risk Contributing conditions I Fluoride exposure (through Yes No drinking water. These molec- ciated with an increased risk of dental caries ular methods have not applied clinically in large [22–24]. Medicaid. Renke Table 3. and/or other siblings last 24 months 7–23 months last 6 months V Dental home: established patient Yes No of record in a dental office General health conditions I Special health-care needs No Yes (developmental. toothpaste) II Sugary foods of drinks (including Primarily at Frequent or prolonged Bottle or sippy cup juice. convenient. making salivary microflora an effective Most of tests regarding caries-associated bac- biomarker of the health and disease status of oral teria require incubation which makes them less cavity [20. energy exposures/day than water at bed drinks. professional applications. the high level ods of caries-associated bacteria test. .

other specific sIgA immunoglobulin electrolytes and small organic molecules. and/or other siblings last 24 months last 7–23 months months (for patients ages 6–14) IV Dental home: established patient Yes No of record in a dental office General health conditions I Special health-care needs No Yes ( over age 14) Yes ( ages 6–14) (developmental. medical. innate immunity factors Cited from Leone et al. supplements. medical syrups) III Caries experience of mother. IgG. professional applications. mealtimes between meal carbonated soft drinks. No carious lesions in Carious lesions in Carious lesions in last 6 caregiver. calcium/phosphate.6 The strength of association between salivary characteristics and caries risk Strong association Weak-to-moderate association No association Flow rate Buffering capacity.3 Saliva and Dental Caries 67 Table 3. physical. open contacts with food impaction VII Dental/orthodontic appliances No Yes present (fixed or removable) IX Severe dry mouth (xerostomia) No Yes Table 3. toothpaste) II Sugary foods of drinks (including Primarily at Frequent or prolonged juice. energy exposures/day drinks. [18] . 1 or No Yes more VI Exposed root surfaces present No Yes VII Restorations with overhangs and/ No Yes or open margins.5 ADA caries risk assessment form for age > 6 Low risk Moderate risk High risk Contributing conditions I Fluoride exposure (through Yes No drinking water. total sIgA. pH. or mental disabilities that prevent or limit performance of adequate oral health care by themselves or caregivers) II Chemo-/radiation therapy No Yes III Eating disorders No Yes IV Medications that reduce salivary No Yes flow V Drug/alcohol abuse No Yes Clinical conditions I Cavitated or non-cavitated No new carious 1 or 2 new carious 3 or more carious (incipient) carious lesions or lesions or restorations lesions or restorations lesions or restorations restorations (visually or in last 36 months in last 36 months in last 36 months radiographically evident) II Teeth missing due to caries in No Yes past 36 months III Visible plaque No Yes IV Unusual tooth morphology that No Yes compromises oral hygiene V Interproximal restorations. carbonated or non. glucose clearance rate/concentration.

Edgar WM. et al. vidual should be paid attention to as well. Splieth C.65(10):1054–62. Infect Immun. Saliva composition and functions: a comprehensive review. Infect obvious reduction of salivary output in one indi- Immun. patients with dry mouth. Activities that low salivary flow rate is a risk factor of dental of lysozyme and salivary peroxidase in unstimulated caries. Are mutans streptococci detected .org/5157.68 W. 2000. tongue and saliva. Chen C. Diseases of the salivary glands. flow. Imfeld T. Yamashita Y. Contreras A. 2011. J Am Dent Assoc. 2011.7(2):87–96. health. 2001. had reviewed 96 references and rate and composition. Leisebach 2012. is an indicator of caries risk still needs more data 19. 2001. 1998. tal caries.174: It has been discussed earlier in this chapter 241–4.137(8):1151–9. indicated sufficient association between caries 15. Renke 3. von Haute J. Rosin M. On the other hand.59(10):3446–50.77:b85. Saliva and oral Adv Dent Res. Microbiological predictors of caries risk. Yu H. Bachmann LM. and function. 1991. Lenander-Lumikari M. 13. complex to the surface protein antigen of Streptococcus mutans. But these Salivary mucins in oral mucosal defense. Scully C. 1972. Xerostomia: an overview. Accessed 22 Feb 2011 20. Saxen L. 1999. Marek C.3 ml/min and the stimu. in healthy young males. J Dent Educ. Clin Oral Invest.97(1):28–46. forms. Binding of sali- A number of studies showed the correlation vary glycoprotein-secretory immunoglobulin A between low salivary buffering capacity and den.85(2):162–9.69(7): normal composition.62(3):203–6. while high buffering capacity indicates 11.9(3):072–80. and the literature is Dent Clin. Eversole R. Koga T. range of salivary flow rate among individuals. Veerman ECI. mucin. Kramer A. Ching V. Murty VL. Manning RH. Dawes C. lactoferrin. www. Lactoferrin: a The level of specific secretory IgA showed a review. The utility of whole saliva to detect the oral presence of 1. lyso. Falduna M.2 Chemical and Physical 3.27(5):761–71. tors including lysozyme. Oral Surg Oral Med risk and salivary innate non-immunoglobulin fac- Oral Pathol Oral Radiol Endod. praline-rich proteins. Adlerova L. pH changes in plaque after strength of association with dental caries eating snacks and meals. Circadian rhythms in human salivary flow Leone et al.8–1. 2001. to demineralization. 14.4. Recovery actino- mycetemcomitans from teeth. Williamson RT. chewing sugared or sugar-free gum. J Physiol. peroxidase/ 16. Oho T. References 21. Asikainen S. Sham ME. Aspects of Saliva J Contemp Dent Pract. found significant associations between caries and 17. Gen values should not be treated as an absolute stan. Oral Dis. Umeda M.aspx. 7. Int J relationship with caries risk. Azevedo LR. Saliva-the better neutralizing capacity and more resistance defender of oral cavity. Mungia et al. Grégio AM. 23. J Periodontol. Slomiany BL. Bartoskova A. Slomiany A. Leone CW. almost equally divided for and against an anticar. 12. 10.8:12–22. 18. 2002.0 ml/min 133–7. Bakker I. An Rosan B. and cystatin recently [29]. Edgar WM. American Dental Association caries risk assessment and further investigation. Humphrey SP. Slots J. American Dental Association Council on Scientific myeloperoxidase. Caries prevention for specific individual submandibular/sublingual sali. A review of saliva: periodontopathic bacteria. ies role of specific secretory IgA. 8. Piotrowski J. Davis CA. Malamud D. 2. Alaluusua S. But if it aspects of saliva as indicators of risk for dental caries in humans. 1993. Oppenheim FG. evidence-based clinical recommendations. No evidence has Essen Oral Med. vary proteins including lactoferrin. divided the chemical and physical characteristics 5. indicate increased caries risk strongly.6) [18]. Adv Dent Res. An update of the etiology and management of xerostomia. Br Dent J. 1996. Demuth DR. Saliva and den- tal caries. de Almeida Pdel V. stather.3: lated salivary flow lower than 0. Su N. Steurer J. 1998. 1991.53(9):457–68. and histatins. of saliva into three groups according to their 6. 4. dard for caries risk screening since there is a wide 9. Saltana N. 2006. Dawes C. 22. Duns Tew: Stephen Hancocks Limited.66(1):115–21. Vet Med.ada. J Periodontol. Hanschke M. 2008. Affairs. Dent.14:40–7. Hegarty A. 2004. albumin. Professionally applied topical fluoride: ins. Porter S. Thenisch NL. Statistical data suggests that unstimulated whole saliva in relation to plaque and gingivitis scores salivary flow less than 0. Lamont RJ. O’Mullane DM.220:529–45. Minder T. 2008. Salivary-agglutinin-mediated adherence of Streptococcus mutans to early plaque bacteria.3(2):58–61. Pharmacol. Physical and chemical zyme. J Prosthet 828–33. J Am Dent Assoc. Fox PC. and their modification by (Table 3. Nieuw Amerongen AV. 1993. Loimaranta V. 4th ed.260–76.

Prediction of 24.42(4):1990208. 25. sugar intake and caries experience as Interaction of age and specific saliva component out- predictors of 2-year and 3-year caries increment. Scand J Dent Res. 28. 2006. 27. de Soet JJ. Nobre-dos-Santos M.40(5):366–74. Steiner-Oliveira C. Dang H. 2008. Identification of caries risk in 1977. 503–8. terial counts. 1989. put on caries.167(3):99–102. Caries Res. Klock B. Early childhood 1993. Brown JP. Caries Res. Ashley FP.85(1):56–63. ditions in 9-12-year old children.27(5):424–30. Holbrook WP. caries and mutans streptococci: a systematic review. 1992. normal dental practice. 2010. Aging Clin Exp Res. .8(1):59–70. Microbiological and salivary con- Oral Health Prev Dent. Sliva CM.20(6): Br Dent J. Cano SM. Saliva and dental caries: diagnostic tests for dental caries risk? A systematic review. Johnson DA. Krasse B. Mungia R. dental caries in pre-school children. 29. Larmas M. de Graaf J.3 Saliva and Dental Caries 69 in preschool children a reliable predictive factor for 26. school-children: salivary buffering capacity and bac. Int Dent Res. Wilson RF. Parisotto TM. Rodriques LK.

L.2 nm thick.4 nm wide. Chengdu. Dental enamel is highly mineralized.1007/978-3-662-47450-1_4 .% collagenous and non-collage- many de-/remineralization cycles [1. and it fibrils forming a three-dimensional scaffold comprises 80–90 % by volume of a calcium-defi. Z. tissue and dissolving the mineral. University of Maryland Dental School. and mag- C. Chengdu. Mature prised of a hydroxyapatite-like mineral contain- human enamel crystallites are 26. to form a less stable. So the min- Sichuan University. tissues (bone or dentine) contain considerably Sound enamel and dentine crystals are com- lower amounts of inorganic minerals. measuring approximately 20 nm in size [3]. The dentinal hard tissue consists of enamel.cn Biomaterials and Tissue Engineering Division. DOI 10..K. Other calcified lites. Chengdu. Dentine and cementum con- bacterial metabolism diffusing into dental hard tain a much greater proportion of organic matrix. State Key Laboratory of Oral Diseases. carbonate.K. Dental Caries: Principles and Management. 30 vol. more soluble apatite. Lei (*) nesium ions are incorporated into the HAP lattice State Key Laboratory of Oral Diseases. Jiyao Department of Endodontics. Prosthodontics and Operative Dentistry. West China Hospital of Stomatology. Xuedong (ed. Sichuan University. Xu Hockin H. approximately 1 out of 10 of the phos- Department of Operative Dentistry and Endodontics. Sichuan University. Baltimore. The process of Dentine is made up of approximately 50 vol. and Zhou Xuedong Dental caries is caused by acids produced from 1. Hockin H. eral of enamel and dentine is much more soluble People’s Republic of China than pure hydroxyapatite or fluorapatite. Sichuan University. People’s Republic of China MD 21201. Chengdu. 68. ions and 1 out of 5 in dentine [4. 2].). and cemen. 5]. Dental nous proteins. and between 100 and The mineral phase of the dental hard tissues is not pure hydroxyapatite (HAP = Ca10 (PO4)6 OH2). Sichuan People’s Republic of China University.3 ± 2. Hydrogen phosphate. Chengdu.% dental caries is a continuum which results from mineral. Xuedong West China Hospital of Stomatology. reinforced by hydroxyl apatite crystal- cient carbonate hydroxyl apatite. e-mail: chenglei@scu.edu. People’s Republic of China X. and 20 vol. State Key Laboratory of Oral Diseases. matrix. Li Jiyao. People’s Republic of China © Springer-Verlag Berlin Heidelberg 2016 71 Z. Chengdu. Sichuan University. But the State Key Laboratory of Oral Diseases.000 nm long [3].% fluids. phate ions in enamel is replaced by carbonate West China Hospital of Stomatology. dentin. partial substitution of fluoride ions for OH groups West China Hospital of Stomatology.3 ± 13. USA Department of Operative Dentistry and Endodontics. Demineralization and Remineralization 4 Cheng Lei. For People’s Republic of China example. ing many impurities and inclusions of other ions. matrix is mainly composed of type I collagen tum.

In the process of rem- and other ions from the tooth [6]. alized enamel to produce net mineral gain.and phosphate-ion concen- trations in the plaque fluid are not sufficient to Dental caries is a disease that is manifested as a maintain the enamel in stable equilibrium. such as by the dental plaque. Calcium (Ca) and phosphate (Pi) ions are continually deposited on the enamel surface or are redeposited in enamel areas where they were 4. low ion concentrations are sufficient to keep dental hard tissues in equilib. calcium and phosphate ions are demineralization is occurring at the atomic level supplied from a source external to the tooth to pro- far before it can be seen visually as gross demin. 4. At physiological conditions 4.2 Investigations cium (Ca) and phosphate (Pi) in supersaturated of De-/Remineralization concentrations with respect to the mineral com- position of enamel. The first stage of ineralization. mouth (Fig. 4.5. or ACID Partly dissolved Enamel/dentin crystal crystal = Carbonated apatite Calclum + Remineralization Phosphate + Fluorlde Fig. higher ion concentrations in vitro model. cavitated carious lesions [7].2. Calcium and phosphate factors and protective factors determines whether are dissolved into the surrounding aqueous phase demineralization or remineralization is proceed- between the crystals [2]. first step in the continuum of the dental caries pro- cess which can eventually lead to cavitation. If the pH drops because of acid produced ied using different kinds of models. 4. De-/Remineralization that is. the calcium. hydrates are metabolized by bacteria in dental De-/remineralization cycles continue in the plaque to produce organic acids. in situ model. This is considered as the ing at any one time [2]. mote ion deposition into crystal voids in deminer- eralization.1 The caries process including Acld reslstant demineralization and Ca10(PO4)6(F)2 = subsequent Crystal flourapatite-like nucleus remineralization to form a coating on crystals low solubility surface on the crystals [2] . biofilm fluid) have cal. animal models. During this step. undersaturation begins. Demineralization is a continual The term “remineralization” is used to imbalance between pathological and protective described mineral gain. fermentable carbohydrates. in the crystal lattice can stabilize the apatite are needed to prevent dissolution of dental hard structure less susceptible to acid attack. tissue. Remineralization is the factors that results in the dissolution of apatite body’s natural repair process for subsurface non- crystals and the net loss of calcium. 5.72 C.1 Models (a neutral pH of 7). dynamic process of de-/remineralization in the the enamel starts to dissolve. The acids diffuse mouth as long as there are factors including cario- into the dental hard tissue through the water genic bacteria.1). Lei et al. phosphate. fermentable carbo. The de-/remineralization process can be stud- rium. and among the crystals and could reach a susceptible saliva present. The balance between pathological site on a crystal surface. thus. The oral fluids (saliva.1 Dynamics Process of lost. At a pH of ca.

Open system bio- inexpensive testing of developing and recently film models are analogous to continuous culture. Two main aspects should be consid. 12]. Each not be relied upon when using complex inocula model has its advantages along with disadvan.2b). 23]. The in situ models are designed to simu- film models or open system biofilm models [15].1. especially for tion of caries-preventive agents (Fig. Various models can be ducibility between experimental runs which can- selected according to different purposes. In vitro pH. involve the use of devices creating conditions that ered when the most suitable biofilm model for a simulate the process of dental caries. situ bacterial community dynamics within the pant compliance issues. Closed system biofilm models are analogous to batch culture and usually based on multi-well 4. mutans biofilm models as The in situ caries model designs are highly . avoid partici. so in vitro biofilm In situ models are also widely used for de-/remin- models are developed to produce artificial caries eralization experiments now. tained at a constant depth by static scraper blades (Fig. reviewed different kinds of tages of in vitro pH cycling: (i) the model can open system biofilm models [15]. (ii) the high level of for de-/remineralization investigations [23. [15. laboratory environment [22.1. 20. Enamel and de-/remineralization investigation was chosen: (1) dentin samples are the hard tissue substrates used to select pure cultures or defined communities or in in situ models to assess de. Silva TC et al.and remineraliza- microcosms and (2) to select closed system bio. attachment biofilm model as a high-throughput duced by ten Cate and Duijsters [13]. scientific control and the resulting lower variabil. require form microcosm biofilms to replicate enabling in fewer staff than in situ studies. in vitro experiments are the much of the complexity and heterogeneity of the most commonly applied methods.1. pensive. 21].2. They are system biofilm models applied in de-/remineral- also broadly used in profile studies for rapid and ization experiments [21. single-species biofilm model are widely used in The induction of artificial carious lesions in de-/remineralization investigations [17–19]. applied an active The modern pH-cycling models were first pro. Zürich biofilm model is another typical closed dated dentifrices for caries control [14].4 Demineralization and Remineralization 73 in randomized controlled clinical trials [8–10]. The constant mimic the dynamics of mineral loss and gain depth film fermentor (CDFF) was widely used involved in caries formation. process [11. et al. Microcosms are able to maintain tages. and are relatively inex. They can be original sample. In situ models lesions [15]. 4.2. properties [16].2a) [18].2. McBain AJ.1 In Vitro Chemical Model plates [18. 25].3 In Situ Model progression of dental diseases. 26. the in vitro evaluation of the efficacy of fluori. demineralization biofilm model for the evalua- cycling models are widely used. For example. 4. Saliva was usually collected to performed over a short period of time. according to whether they are “closed” or “open” tions known to influence de-/remineralization with respect to nutritional availability [15]. 27]. 24]. late the natural process of de-/remineralization Streptococcus mutans are considered the most and also to provide information in a short period cariogenic microorganisms in dental biofilm due of time without causing damage to the natural to their capacity to use dietary carbohydrates to teeth of volunteers [28]. These models serve as a synthesize extracellular polysaccharides (EPS) link between the clinical uncontrolled situation and because of their acidogenic and aciduric and the highly controlled laboratory experiments. marketed products [9].2 In Vitro Biofilm Model Dental plaque biofilms play a pivotal role in the 4. tion [8]. The CDFF allows the generation of large ity intrinsic to in vitro models. and (iii) it requires numbers of replicate biofilms which can be main- smaller sample size [14]. And S. 4. bovine and human teeth is an important tool to Multiple species biofilm models using defined study strategies for the prevention or treatment consortia could achieve a high degree of repro- of carious lesions. There are several advan. But they cannot replicate the oral Biofilm models can be divided into two groups environment with all of the biological varia.

control where possible [8]. aerial Tie bar view of a pen) PTFE seal Bottom plate Outlet for waste medium Drive shaft Fig.2. Lei et al. Methods ations.2 Detection and Measurement For many reasons—particularly time consider.’s investigations.2 In vitro biofilm models. (b) CDFF [15] variable because of the variations of the in situ uating fluoride dentifrices: Francis’ hypomineral- study designs. 4. ized area model. All in situ studies must have appro. (a) an active attachment biofilm model [18]. the priate controls including a positive and negative Connecticut model. methods. . and attendant costs— rodents have been the most commonly used Various techniques have been used to investigate the species for experimental caries studies [21]. 4.1. animal availability. a b Medium inlets Sampling port Gas Top plate Glass housing Sprung scraper blade Turntable (expanded. Gaffar’s CARA rat model.2. the process. mineral loss and gain during de-/remineralization According to Stookey et al. and the Indiana model [29].4 Animal Model 4.74 C. including destructive and nondestructive following rat caries models could be used for eval.

A microradiographic image is made on covering a range from 0.1 mM rhodamine B) and analyzed using 4.95 g/cm3 [39]. Parameters of interest able to identify tissue-emitting fluorescent signal are mineral loss (Delta Z in Vol%. reported a linear correlation between CT exactly the same lesions [31]. To prepare the intensity (or gray scale value) and the mineral samples for TMR investigation.2. a diamond tip of known dimensions is When high-intensity blue light illuminates the pressed onto a surface with a given load and dura. expected as the high organic content. The intensity of the tooth nanoindentation yields hardness and reduced image at a demineralized area is darker than the elastic modulus in the SI unit of Pascals (Nm−2) sound area. quantitative analysis of the de. and the mineral vol% and position of the to sound dentine [43].2. high-resolution film by X-ray exposure of the sections together with a calibration aluminum 4. and content of the enamel. Quantitative light-induced fluorescence (QLF) is tion (ultra-microindentation) [34]. tion based on CT intensity data [31]. It is a noninvasive. and respect to dentine mineral loss [11].4 Demineralization and Remineralization 75 4. The microindentation technique yields data detected by an intraoral camera. so it cannot be verse the CT intensity into mineral content. The software of QLF systems can [35].25–3. lesion depth.5 Quantitative Light-Induced de-/remineralization investigations: microinden. Optical coherence tomography (OCT) is a three- dimensional optical imaging technique which 4. thin slices (about density using three apatite phantoms. eralization or remineralization of human enamel.4 Confocal Laser Scanning step wedge. So it is possible to measure and visu. There are two kinds of indentation techniques for 4.2. The emitted fluo- in arbitrary units. Fluorescence tation (surface hardness) [32] and nanoindenta. ratio or average loss of min. This was lesion volume [45–47]. but uses Micro-CT investigation is a nondestructive high-frequency light (around 820 nm) instead of method to measure the mineral changes of dental high-frequency sound [48].2. The mineral can be automatically Microscopy calculated from the gray levels of the images of Confocal laser scanning microscopy (CLSM) is section and step wedge.2. revealed that surface hard.2.2. stained thick enamel samples with a fluorescent dye (0.1 Transversal alize longitudinal mineral changes during de.and remineraliza- ogy of and the change in mineral content of den. the resultant autofluorescence of enamel is tion. and thus. Moron BM et al. hard tissue.07 to 2. Published TMR or contact-microradiography is a highly papers proved that micro-CT could offer the sensitive method used to measure the morphol. found a good linearity using six phantoms surface. Some previous studies subsurface layer and lesion body [32. teeth.2. the elastic properties of the dentine influence the 4. lesion and can be used to detect the mineral loss of den- depth (Lesd in μm). tation.2.2 Indentation Techniques CLSM for quantitating demineralization and rem- Indentation techniques have been used to measure ineralization of enamel specimens [44].μm). covering a range of 0.and Microradiography (TMR) remineralization in the same lesion [37]. But the method is usually point of using micro-CT is to find out how to con- destructive to dental hard tissue. the hardness of the dental hard tissue surface.2. usually Knoop hardness number rescence has a direct relationship with the mineral (KHN) or Vickers hardness number (VHN).14 g/cm3 [38]. tal hard tissue [40–42]. Schwass tine samples) are cut perpendicularly to the tooth et al. During the a quantification system for assessing early demin- process of both microindentation and nanoinden.2. The key tal hard tissue [30].3 Micro-CT works in a similar way to ultrasound.2. Neves used to study any longitudinal mineral changes in et al.6 Optical Coherence Tomography hardness measurement [36]. cross-sectional imaging system that can visualize . the linearity 80 μm for enamel samples and 200 μm for den. 33]. process the image to provide user quantitative ness analysis should not be interpreted with parameters such as lesion area. Demineralizing dentin has eral content in the lesion area (Delta Z/Lesd in a strongly increased autofluorescence compared Vol%).

76 C. Lei et al.

the internal structures nondestructively [49]. dental hard tissue to acidic challenges, and thus
Amaechi et al. developed a quantitative method inhibit lesion development [7, 56]. In addition,
to detect the demineralizing lesions of dental calcium-fluoride-like deposits could form on den-
enamel using an OCT system [50]. This system tal hard tissues and act as a protective barrier on
was able to collect A-scans (depth versus the surface and serve as a reservoir for fluoride
reflectivity curve), B-scans (longitudinal images), [53]. Other researchers have some different opin-
and C-scans (transverse images at constant ions. They demonstrate that the incorporation of
depth). The area (R) under the A-scan could be fluorides into the mineral components of enamel
quantified to indicate the degree of reflectivity of only slightly reduced its solubility [54, 55, 57].
the tissue. Small amounts of free fluoride ions in solution
around the dental hard tissue play a much more
important role in inhibiting demineralization.
4.3 Methods to Influence These fluorides have a much greater caries-
the De-/Remineralization protective potential than a large proportion of FAP
Process incorporated in enamel mineral [58]. Free fluoride
ions are in part adsorbed onto the crystalline sur-
4.3.1 Traditional Methods face and are in dynamic equilibrium with the fluo-
ride ions in solution around dental hard tissue. So Fluoride it forms an equilibrium or supersaturation relative
Fluoride was introduced into dentistry over 70 to fluor(hydroxy)apatite, and the adsorption of
years ago, and it is now recognized as the main fluoride on the crystals can offer direct protection
factor responsible for the dramatic decline in car- from demineralization. Therefore, according to
ies prevalence that has been observed worldwide this theory, fluoride should be present in the right
[51]. Fluoride can be obtained in two forms: sys- place (biofilm fluid or saliva) and at the right time
temic and topical. Systemic methods include (when biofilm is exposed to sugar or right after
water fluoridation, salt fluoridation, milk fluori- biofilm removal), and even small amount of fluo-
dation, and supplements. Later in the 1940s, the ride (below ppm values) available is effective.
well-conducted water fluoridation program was In addition to its ability of inhibiting demineral-
established in the United States. Though some ization, fluoride is thought to be effective to pro-
dentists and researchers have conflicting opin- mote remineralization. However, fluoride’s ability
ions about their safety and benefits, these sys- to enhance net remineralization is limited by the
temic methods are still recommended in many availability of calcium and phosphate ions [59]. If
countries and receive support from recognized adequate salivary or plaque calcium and phosphate
international committees and associations. Due ions are available, fluoride ions can drive the rem-
to the widespread application of fluoride and the ineralization of extant non-cavitated caries lesions.
updated knowledge about its mechanisms of Fluorhydroxyapatite forms more rapidly even in
action, topical applications of fluoride (e.g., fluo- slightly acidic condition than do the other calcium
ride toothpastes, gels, varnishes, and mouth- phosphate phases, so fluoride can accelerate and
washes) are considered to be more effective promote remineralization of dental hard tissue.
methods for caries prevention than systemic use It has been demonstrated that fluoride used in
of fluorides [52]. enamel remineralization also work in dentine
It is believed that fluoride could inhibit demin- remineralization, and even their remineralization
eralization and enhance remineralization [7, 53– mechanisms are similar [60, 61]. However, dentin
55]. Numerous studies were designed to investigate demands a considerably higher fluoride concen-
the mechanism of fluoride in inhibiting demineral- tration in its surrounding solution than enamel
ization of dental hard tissue. According to previous does to reach an equivalent degree of demineral-
studies, fluoride could incorporate into the enamel ization inhibition [62].
apatite structure, enhance the resistance of the

4 Demineralization and Remineralization 77 Calcium Phosphate continue only at the hydroxyapatite (001) plane
Calcium and phosphate ions play important roles or along the c-axis, which is the pattern of crystal
in enhancing remineralization of dental caries. growth during amelogenesis. Therefore, CPPs
Investigators have tried various solutions are able to regulate anisotropic crystal growth
containing calcium and phosphate ions in their and also inhibit crystal demineralization in the
experiments, in which solutions contained enamel subsurface lesion [68].
between 1 and 3 mM calcium ions with phosphate The amorphous calcium phosphate (ACP) is an
ions in the ratio of 1:1 [63, 64] or 1.66:1 [63],often important compound because it is a precursor that
with the addition of 1 ppm fluoride ions. Higher can convert to apatite, similar to the minerals in
concentrations are difficulty to be used because tooth enamel and dentin. ACP is an unstabilized
of the instability of the solutions. So the low calcium and phosphate system. When a calcium
solubility of calcium phosphates, particularly in salt (e.g., calcium sulfate) and a phosphate salt
the presence of fluoride ions, limited the clinical (e.g., potassium phosphate) are delivered sepa-
application of calcium and phosphate rately, the calcium ions and phosphate ions are
remineralization systems. Therefore, novel mixed and result in the immediate precipitation of
calcium-phosphate-based delivery systems are ACP or, in the presence of fluoride ions, amor-
developed to combat the demineralization of phous calcium fluoride phosphate (ACFP). In the
dental hard tissue. New commercial products are intraoral environment, these phases (ACP and
available based on three types of novel systems— ACFP) are potentially very unstable and may rap-
crystalline, unstabilized amorphous, or stabilized idly transform into a more thermodynamically
amorphous formulations. stable, crystalline phase (e.g., hydroxyapatite and
fluorhydroxyapatite). However, before phase
transformation, calcium and phosphate ions should
4.3.2 Novel Methods be transiently bioavailable to promote enamel sub-
surface lesion remineralization. CPP–ACP and CPP–ACFP
CPP–ACP has been shown to promote Natural Medicine
remineralization of initial enamel lesions and to Previous studies indicated some nature medicines
prevent demineralization in laboratory, animal, were able to influence the de-/remineralization
and human experiments [59, 65]. Casein balance of dental hard tissue. The extracts of
phosphopeptides (CPP) can stabilize calcium and Galla chinensis (GCE) could inhibit the deminer-
phosphate as nanoclusters of ions through the alization and enhance the remineralization of
formation of amorphous nanocomplexes enamel and dentin [69–72]. In addition, this poly-
(diameter of 2.12 nm) in metastable solution phenol compounds had combined effects with tra-
[66]. But it can also prevent the growth of the ditional remineralizing agents, like fluoride [69],
nanoclusters to the critical size required for nano-hydroxyapatite [73]. However, the mecha-
nucleation and phase transformation [65]. CPP nism of GCE is still unclear, and more investiga-
contains the active sequence Ser(P)-Ser(P)- tions are still needed.
Ser(P)-Glu-Glu. Phosphorylated seryl residues
are regarded as responsible for the interactions Laser
between casein and the calcium and phosphate Several types of lasers, such as erbium-doped
ions in the nanocomplexes [67]. yttrium aluminum garnet (Er:YAG) [74, 75],
CPPs can bind to the more thermodynami- neodymium-doped yttrium aluminum garnet
cally favored surface of an apatite crystal face in (Nd:YAG) [74, 76], and carbon dioxide (CO2)
the caries lesion due to its high binding affinity [76–79], with different parameter settings, have
for apatite. And CPPs prefer binding to the (100) been used for caries inhibition. It is believed that
and (010) faces of hydroxyapatite crystals the use of the high-intensity laser on the dental
(Fig. 4.3). So crystal growth would be allowed to structure can lead to a more acid-resistant sur-

78 C. Lei et al.

a c



b d

b x

Fig. 4.3 A molecular model of the Ser(P)-Ser(P)-Ser(P)- peptide rendered in CPK and the crystal atoms in ‘line’
Glu-Glu motif bound onto the face of hydroxyapatite form; (b) as in (a), but viewed from above, looking down
(HA). The atoms are colorcoded as follows: calcium (1) on the HA (100) face; (c) as in (b), with the peptide dis-
atoms are light-blue crosses, calcium (2) atoms are dark- played in stick form and the atoms in the HA surface
blue crosses, oxygen atoms are red, phosphorus atoms are within 0.25 nm of the peptide rendered in CPK; and (d) as
magenta, carbon atoms are green, nitrogen atoms are blue, in (b), with the peptide displayed in stick form and the
and hydrogen atoms are grey. The symbol X indicates a atoms of the peptide within 0.25 nm of the HA surface
crystallographic axis projecting into the paper. Four views rendered in CPK. [68]
are presented: (a) a side view along the c-axis, with the

face, and previous investigations showed that creation of functional materials, devices, or sys-
lasers could inhibit enamel demineralization and tems through control of matter on the nanometer
reduce enamel permeability [80]. scale (1–100 nm). Nanotechnology has motivated
mimicking of the nanostructural features of natu- Nanoparticles ral human enamel and development of bioin-
Currently, nanotechnology is experiencing rapid spired strategies for remineralization and caries
growth, with many potential applications in car- therapy, respectively [81]. Previous researches
ies prevention and treatment. It is defined as the have tried to apply nanoparticles in dental caries

4 Demineralization and Remineralization 79 a b c Fig. CaF2 nanoparticles can be synthesized using Clinical investigations indicate that secondary the same spray-drying apparatus. evaporated and expelled into an exhaust hood. filler par- (approximately 5–100 nm) and near-nanoscaled ticles. a spraying of the superficial layer of initial caries lesions solution was prepared by dissolving calcium measuring 20–40 μm. Nanoparticles of ACP can be synthesized via a ter.4 TEM micrographs of the spray-dried nanoparticles: (a) small ACP nanoparticles. chemical reactivity.4). and Ca(OH)2 + NH4F → CaF2 + NH4OH. 84]. When the sizes (CaP) particles and calcium fluoride particles of particles are reduced from micrometer to have been used as fillers in resin composites nanometer. rinsing solutions as commercial products. phosphate face area. average dentist’s practice time [88]. [90]. These additives enable activity are all altered [83]. and biological (PO4). especially and NH4F. For example. The application of the resin composite to release calcium and phos- nanoparticles in dentistry can be categorized into phate when the pH is dropped down under in vitro two directions: preventive dentistry and restora. various types of nano-sized ion-releasing nanofillers include nanoparticles of hydroxyapatite or calcium carbonate are applied dicalcium phosphate anhydrous (112 nm in size). Two reasons for dental restoration failure. including spherical. And some nanocrystals The dried particles were collected by an electro- have been incorporated into toothpastes or mouth. hardness. Carbonate hydroxyl solution was sprayed through a nozzle into a apatite nanoparticles have also been reported to be heated chamber. Briefly. (b) ACP cluster. and needlelike nanoscaled particles try to improve the resin compositions. and cure conditions. or fluoride ions. The water and volatile acid were effective in repairing micrometer-sized tooth-sur. 84. These resin-based CaP or CaF com- dramatically. These calcium and phosphate or fluoride In recent years. active sur. 4. Investigators cubic. And the two solutions are atomized the resin composites [87]. Calcium phosphate devices (up to micrometers) [82]. The NH4OH replacing them consumes nearly 60 % of the is removed as NH3 and H2O vapors [96]. conditions. the resultant properties can change (Fig. Approximately half of leading to the formation of CaF2 nanoparticles: all dental restorations fail within 10 years. and so on [91–95]. nano-hydroxyapatite particles (10–20 nm diame. A two-liquid caries and restoration fracture are still the main nozzle was employed during the procedures. 4. (c) CaF2 nanoparticles [89] prevention and treatment. posites can release calcium (Ca). solutions are mixed during atomization: Ca(OH)2 its the longevity of dental restorations. face defects in vitro [86]. which lim. static precipitator. but little remineralization carbonate and dicalcium phosphate anhydrous could be obtained by nano-hydroxyapatite in the (CaHPO4) into an acetic acid solution. Then this body of the lesion [73. to combat early caries lesions [73. 85]. 60–80 nm length) promotes remineralization spray-drying technique. . providing caries-inhibiting properties tion dentistry [81]. Some amorphous calcium phosphate (ACP) (116 nm in in vitro studies indicated that 10 % suspension of size).

Ccahuana-Vasquez RA. Cutress and experimental rat caries studies: a comparison. et al. Tovo MF. Hannas AR.50(4):353–80. Delbem AC. Tagami J. in vitro studies. Silva TC. 1982. Giertsen E. Featherstone JD. nonbiological surfactants strongly limits their Caries Res. including nonphysiological tempera- 14. Caries Res. The chemistry of enamel car- organisms produce minerals. Yu numerous evidences indicating that organic tem. 2008. Brookes SJ. 2010. Alves the clinical application of biomimetic approaches KM. Franco KS. Secondly. pH-cycling models for clinical practice. Dental caries: a dynamic disease evaluated by a biofilm caries model. Adv Appl Microbiol. BMC find special templates to achieve biomineraliza. Munoz-Sandoval C. Machado MA. Crit Rev Oral Biol Med. Eichhorn M. Caries Res.5(8):565–9. J Dent. Featherstone JD. 1991. and characterization of carbonated apatites.2(3):283–96. Caries Res. Hannig M. ten Cate JM. Bagnato VS. Cury JA. 2011. Lei et al. McBain AJ. Wiegand A.3. ten Cate JM.11(4):481–95. Munoz MJ. J Appl Microbiol. Chapter 4: In vitro biofilm models: an talline hydroxyapatite micro-ribbons were used overview. Remineralization caries.53(3):286–91. Okada A. Featherstone JD. Thurnheer T. Mechanistic aspects of the interactions between fluoride and dental enamel.16(3):201–10. 2008. Cariogenicity of soluble starch in oral in vitro biofilm 5. process.11:13. 2010. Spiguel MH. Buchalla W. TW.24(2):135–41. dental hard tissue is unable to heal models. Featherstone JD. 6. 2012. Loesche WJ. ture or pressure [98]. Moron BM.80 C. Aust Dent J. Design of a randomized controlled double-blind crossover clinical trial to assess the effects of saliva dental hard tissue. 3. 2011. Adv Dent Res. 1983. evidence for a dynamic disease process.43(4):302–7. tissues. often to mineralized ies. Understanding the 94–7.18(4):316–34. bioinspired formation of enamel-like structures 2013. mutans biofilm 37 °C [99]. Exterkate RA. tion of dental hard tissue in vitro [89]. mechanism of dental hard tissue inspired the 10. analysis. 2009. 17(3):200–11. For example. model to evaluate antimicrobial substances and enamel demineralization. However. 2012. Comar LP.69:99–132. H. Microbiol Rev. J Appl Oral Sci.83 Spec No C:C39–42. dentifrices for caries control: strengths and limitations. Nelson DG. Wolf O. Kirkham J. Nanomaterials in preventive 20. as substitutes for amelogenin templates to control 16. Duncan JF. 1995. there are some problems about 12. Hayati F. 13. artificial biofilm induced secondary caries model for 4. Calcif 21. most of biomi. S. Matin K. Tissue Int. Kitasako Y.24(2):129–32. biomineralization. Firstly. Different protocols to produce artificial dentine carious lesions in vitro and in situ: plates or scaffolds would be a prerequisite for hardness and mineral content correlation. Braz Oral Res. Gmur R. Oral Health. Alternating demineraliza- metic approaches need various hydrothermal tion and remineralization of artificial enamel lesions. 1.3 Biomineralization tion behaviour of synthetic apatites. Effect of fluoridated 2004. Effect of carbonate and fluoride on the dissolu. . the suspected biocompatibility of remineralization process: an in vitro and in situ study. et al. Application of an References active attachment model as a high-throughput demin- eralization biofilm model. The continuum of dental caries – 19. Role of Streptococcus mutans in human HAP crystallization at biophysical conditions at dental decay. Rios D. Robinson C. The formation of teeth is a process of 7. which cannot be applied in Honorio HM. 2000. Pereira AF. Strafford S. Shore RC. Nat Nanotechnol. 1982. Guggenheim B. 2009. single crys- 15. Adv Dent Res. Reynolds EC. Nelson DG. An dentistry. Buzalaf MA. 17. So some investigators have in vitro evaluation of the efficacy of fluoridated focused on the biomimetic approaches in physio. Buzalaf MA.47(2):162–70. Kielbassa researchers who studied the remineralization of AM. Featherstone JD. [97]. Ccahuana-Vasquez RA. Zero DT. Though traditional methods Crit Rev Oral Biol Med.9(3):175–93.34 Suppl 2:S69–81. Tschoppe P.56(1):40–7. Delbem AC. Duijsters PP. 18. Evaluation of laser fluorescence in the monitoring of the initial stage of the de-/ in vitro. milk on enamel and root dentin demineralization 2. 2010.40(1):41–7. 4. Numerous studies have tried to substitutes on bovine enamel and dentin in situ.105(3):829–36. Kramer PF. Martus P. Cury JA. The application of in vitro models to research on demineralization and remineralization of surface and subsequent cavitation due to its the teeth. White DJ. J Dent Res. conditions. There are 11. Giacaman RA. Hannig C.46(5):460–6. Aust Dent J. discussion non-regenerative nature. Preparation. Magalhaes AC. Buzalaf MA. Biomineralization is the process by which living Wood SR. 1986. 2012. clinical application. Caries Res. have been proven to be effective to combat dental 8. Cochrane NJ. and repair itself after demineralization of the 9. logical-like condition.

Adv Dent Res. A studies. 2010. 53. 1999. Marshall Jr GW. Caries model. Autofluorescence and mineral shiitake mushroom on composition and cariogenicity content of carious dentine: scanning optical and of dental plaque microcosms in an in vitro caries backscattered electron microscopic studies. and bovine dentine compared with human enamel. Pereira-Cenci T. Review on fluoride. 2001.2011:135034. Schemehorn BR. 32. Caries Res. Cenci MS. Ruben J. Sinhoreti MA. Soares PC. Zaura E. ten Cate JM. Anderson P. Coutinho E. Purton DG. Banerjee A. Puppin-Rontani RM. Confocal laser to problems of cariology. Van Meerbeek B. 2008. 2012. Stookey GK. Relationship between gap size and dentine 40. JM. Caries Res. 42. Stinson Biol. Time JM. Deng DM. Honorio HM. Effect of Galla chinensis on in an era of decreased caries and increased fluorosis the in vitro remineralization of advanced enamel prevalence.32(8):591–602.22:97–114.254(5035):1178–81. Stookey GK. Ten Cate caries research. coherence tomography to detect demineralized regions radiographic studies of rates of in vitro demineraliza. Zero DT. discussion 31–4. de Fucio SB. secondary caries formation assessed in a microcosm Bedran-Russo AK. Guggenheim B. 1999. Arends J. J Biomed Biotechnol.105(5 Pt 2):461–5. Res. Nango N. 1989. J Public Health Dent. ten Cate JM. operator-. Bertassoni LE. 1991. et al. Pretty IA.43(8):649–56. Wu CD. 2008. Hoogenkamp MA.23(5):342–4. Barbour ME. Fontana M. Pessan JP. Elliot JC. Use of optical coherence tomography for alization of dentin. Gonzalez-Cabezas C. system of calibrating microtomography for use in 23.32(3):219–26. Eur J Orthod. Podoleanu AG. Caries Res. sis on calcium fluoride mechanisms in caries preven- Jaecques SV. ten Cate JM. In situ caries models. Biofouling. and with early artificial caries lesions using confocal 24. Huang D. Analoui M. MC. Choo- Spec No:924–8. Proskin HM.38(3): scanning microscopic analysis of the depth of dentin 212–22.9(3):214–30. 2011. Giertsen E. Habelitz S. et al. Effect of bleaching on sound enamel biofilm model. Amaechi BT.31(4):533–40. The laboratory assessment of Oral Rehabil. caries-like lesions in primary and permanent teeth. Nakashima S. 1997. Res. Mechanisms of action of fluoride for caries con- dependency of microhardness indentations in human trol. 1998. Sowa MG. Boyde A. Caries Res. The J.51(1):23–41.43(4):314–21. Giannini M. Ogaard B. 2011. Science. demineralization and antimicrobial dose–response 39. 46. Swain MV. Vivan Cardoso M. 26. 1995. Ripa LW. Lund RG. Effect of Galla chinensis on growth and metabolism 41. Signoretto C. Edgar WM.4 Demineralization and Remineralization 81 22. Greene AL. 208–13.71 48. by Streptococcus mutans biofilms grown in the Fischer GM. 1997. 2010. The effects of fractions from 43. light-induced fluorescence systems: an in vitro study. Lukantsova 30. Nakata K. Levinkind M. Cury JA. Demineralization of dentin 44. Application of the Zurich biofilm model Sobrinho L. 2009. Stookey G. van der Veen M. Nikaido T. J Biophotonics. mouthrinses. Caries Res.32(5):385–92. Dunipace AJ. 1991. Caries Res.32(5):312–9. J 35. 2009. Jackson DA. 2004. Warrick JM. Arends J. 1995.and re-mineral- of mineral density for monitoring enamel remineral. discussion loss in vitro. Cheng L. Gmur R. Buzalaf MA.31(2):125–31. Evaluation of surface 50. enamel erosion: a review. Rogers JA. Eur J Oral Sci. Braz Dent J. Smith LP. 2003. structural and mechanical changes following reminer. . Guggenheim M. Cenci MS. de Carvalho FG. Buijs MJ. WG.36(11):900–6. Lin CP. Adv Dent Res. 27. J Dent. and self-applied gels) 37. Witjes M.19(2):139–44. 2012. Higham SM. Lagerweij M. Dos Santos PH. Higham SM. Dent Mater J. Caries 28.9(3):198–207. assessment of dental caries: quantitative procedure. 34. Eckert GJ.38(1): enamel remineralization using microradiography and 54–61. A correlational study. quantitative light-induced fluorescence. 45. Pugach M. In vitro remineral- of microcosm biofilms. Demineralization and remin.28(12):1092–3. ten Cate JM. Popescu DP. Bedran-Russo AK. ization adjacent to bonded orthodontic cleats using ization progress.25(3):217–23. Clasen AB. Zhou X. with special empha- 38. confocal microscopy. fluorescence techniques to quantitate early mineral frices. Azevedo MS. van de Sande FH. Exterkate RA. A. An in vitro biofilm model for enamel 2010. tion. Optical coherence tomography. Rees JS. Swanson EA. Arch Oral 49. laser microscopy. Berger SB. tion in human and bovine dental enamel. A comparison of methods using optical 33. Miller LL. 2011. Friesen JR.45(2): ization effects of grape seed extract on artificial root 87–92.4(11–12):814–23. 2011. 25.2(1):15–20. 1998. 31. 29. Chang W.27(9):1057–63. Schwass DR. Caries Res. lesions.43(2):97–102. Relative ability of laser Animal caries models for evaluating fluoride denti. 2011. Scanning micro. Huysmans titative evaluation of caries excavation.33(3):220–6. An approach to normalizing micro-CT depth profiles in vitro detection of early enamel de. Ando M. Neves Ade A. 1998. Marshall SJ. 1992. Schuman JS. Herkstroter FM. Hall AF. Monogr Oral Sci. Scanning. Ciric L. A critique of topical fluoride methods (den- Caries Res. 2004.26(6):579–88. 2004. J Dent Res. Ando M. Tagami 47.57(6):334–41. Leichter JW.23(2):110–5. Xie Q. caries. eralization evaluation techniques. 52. Li Y. Dent Mater. Int J Oral Sci. Correr- Thurnheer T. Papetti Braz Dent J. Acta Odontol Scand. Li J. J Dent. Micro-CT based quan. Experimental intra-oral caries L. ten Cate 36. Pender N. in teeth. et al. The validity and repeatability of three models in fluoride research. Measurement of constant depth film fermentor. ten Bosch JJ. Cheng L. Hewko MD. 51. Pavan S. tifrices.

Trop Med Hyg. 2008. Caries Res.24(2):53–7. EC. J Dent Res. Li J. Remineralization poten- plexes. Li JY. The effect 63. Harless JD. J Dent Res. Maung NL. J Dent Res. Hao YQ. nano-hydroxyapatite and Galla chinensis on reminer- 56.66(11):1640–3. Ceballos L. of Galla chinensis and their combined effects with J Oral Sci. in vitro. O’Connor CJ. Cai F. In vitro evaluation of lesions in enamel.35(1):41–6. Effect of com. and physical behavior considerations. phopeptide-amorphous calcium phosphate nanocom. posite restorations. enamel in a human caries model. Duijsters PP. Nakashima S. 1987. Featherstone JD. Barrett-Vespone NA. Reynolds EC. Huang S. 1998. Nanotechnology and its role in calcium phosphate: the scientific evidence. Summary of dis- Effect of Galla chinensis extract and chemical frac. Dederich DN. Li J. 74. II. tism in developing nanostructured inorganic matrices 70. Caries Res. for drug delivery. Palazzo B. Cai F. phosphate and fluoride. of two bovine root lesions morphous in vitro.36(6):423–9. J Biol Chem. try. Wohland T. Ellwood R. J Dent Res. Gao S. tooth enamel. Jing Y. 79. for dental posterior restorative composites: clinical. 1986. 1983. solution on tooth demineralization.102(1):1–2. enamel demineralization after Er:YAG and Nd:YAG 58. Physicochemical characterization of casein phos. Cheng L. Li W. Oral Biol. Effect of Galla chinensis on the remineralization data.45(5):460–8. Cochrane NJ. Wefel JS. 57. 2007. Adv Dent caries therapy. Chu JP. . Oregon. Effects 62.29(4):1349–55.65(1):2–11. eralization of human carious dentine in vitro. 78. Bahar A. Rehardening of of fractional CO laser irradiation on remineralization softened enamel surfaces of human teeth by solutions of enamel white spot lesions. Casein phosphopeptide-amorphous 81. Reynolds EC. Cai F. Caries Res. Scand J Dent Res. Sano H. Wang B. 1973. Reynolds ogy on the control of infectious diseases. Garcia-Godoy F. Lin YT. Yu H.34(4):281–8. Ahrari F. 2012. Yoshie M. Kantorowitz Z. Koulourides T.18(11):1351–6. 2011. Arends J. Arends J. Poosti M. Hao Y. Flaitz C. Castellan CS. Liang QQ. 2001.89(11):1187–97. Zhou X. Caries Res. Huq NL. ten Cate JM. 84. Photomed Laser Microradiographic study of demineralization of shark Surg. Huang S. Res. Hannig M. Remineralization of bovine cial caries-like lesion progression in dental enamel.25(1):39–45. et al. 2005. Luiz AC. J Dent. 2009. The use of saturated DCPD in 80.38(10):811–9. 3893–946. Dent Mater. Kolesnichenko VL. 2010. Allaker RP. Expert Opin Drug Deliv. 2009. Toledano M. Tsai CL.14(1):46–9. 2008. Roveri N. Enamel subsurface lesion remineralisation with inorganic nanoparticles. Potential impact of nanotechnol- 67. Que KH. Davies R. Sakaguchi RL. Ren G. 2012. Iafisco M. Am J Dent. Liao H. Najjaran H. 54. 64. Osorio R. The role of biomime- in vitro. J Dent Res. Hicks J. 5(8):861–77. Hsu CY. Cushing BL. dentifrices containing 5. 1991. 82. Cross KJ. pounds of Galla chinensis on remineralisation of ini. tial enamel carious lesions in vitro. ten Cate JM. chemis- 71. J Dent.79(9):1725–30. Xie tion on tooth demineralization.36(5):369–73.51(1):69–77. Zou L. Oregon Health and Science Dent.100 ppm fluoride. test dentifrice containing nano-sized calcium carbon- 69. 2002. on in vitro secondary caries formation around com- Morgan MV. Combined effects of Caries Res. Dent Res. Gao S. J incisor root lesions in vitro: the role of the collage. 2000.17(3):193–9. 87.189:226–7. ten Cate JM. Palamara JE. J Dent. University. 83. Hsu CY. Review of the current status and challenges 35(5):383–7. Reversal of primary root caries using matrix on inhibition of enamel demineralization. Duijsters PP.36(12):999–1004. Saranathan S. Zhou XD. tide-amorphous calcium phosphate. In vitro acid 87(4):344–8. 76. Ruben J. fluoride on remineralization of initial enamel lesion 86. Petersson of low-energy CO2 laser irradiation and the organic L. Caries Res. Int J 55. Effect of a tooth enamel. Cheng L. CO2 laser inhibitor of artifi- 61.104(9): casein phosphopeptide stabilised solutions of calcium. et al. 1988. 2008. 66. 2014. Caries Res. Caries Res.4(3):152–6. Christoffersen J. Cochrane NJ. Huang ST. 73.25(2):85–90. ER-YAG laser pretreatment effect 59. Seka W.000 and 1. J Dent. New approaches to enhanced remineralization of 85. Pigman W. Rolla G. Portland. cussion from the Portland Composites Symposium tions on demineralization of bovine enamel in vitro. nous matrix. 65. Zhang L. Rowles SL. Chemical data. Reynolds in vitro study. Adv Dent Res. Borsboom P. Levine RS.21(1):3–6. Chow LC. Bezinelli LM. 2007. 2000. Dijkman T. The nature of early caries Mendes FM.82 C. 1961. Fluoride and casein phosphopep. 72. Perich JW. Klont B. 2008. Takagi S. Lynch E. tial of nano-hydroxyapatite on initial enamel lesions: an 68. J (POCOS) June 17–19. Jordan TH. Fried D. fluoride on enamel demineralization/remineralization 2010.42(2):88–97. Yu H.280(15):15362–9. of calcium phosphates. Moosavi H. 2001. Chem Rev. Chang HW. Nature.77(6):1397–403. Hannig C. Reynolds Recent advances in the liquid-phase syntheses of EC. 2007.21(1):25–9. 2004. 2008. Huq NL. Effect of compounds ate on remineralization of enamel lesions in vitro. Baysan A. Cross KJ. Wefel JS. laser irradiation on primary teeth. Lasers Med Sci.96(3):209–11. Cheng L. Influence of fluoride in Oral Sci.17(6):513–9. Lopes RM. 2008. Lei et al. Further studies on the remin. Ogaard B. modulated by Er:YAG laser (Part 1)–FRAP. Guo B. 2005. resistance of CO2 and Nd-YAG laser-treated human 60. 75. Cheng L.35(10):787–93. Shen P. De PEC. Microradiographic HH. I. Walker GD. Influence of fluoride in solu. Cueto H. 1983. Burrow MF. Enamel diffusion remineralization of artificial caries lesions in vitro. Cochrane NJ. Effect of tooth-bound alisation of initial enamel lesion in vitro. Trans R Soc EC. Arch 77. et al. 2004. Hao Y.

23(12):1482–91. Jiang D. .86(4):378–83. Moreau JL. and PO4 release: effects of reinforcement.27(8):762–9. dicalcium 99. Langmuir. Nanotechnol.89(7):739–45. Biological synthesis of tooth enamel instructed by posite. Yamagishi K. 2002. 2005. Frost PM. J Nanosci 94. and F release for caries inhibition. an artificial matrix. Xu HH. 96. J Dent Res. Weir MD. Synthesis of dental for caries inhibition. Sun L. Nature. containing amorphous calcium phosphate nanoparticles 98. Moreau JL. et al. Huang Z. nanocomposite with high strength and fluoride ion 97.4 Demineralization and Remineralization 83 88. Chow LC. Onuma K.26(5):2989–94. based dental nanocomposite. Xu HH. 2010. Novel CaF(2) 4261–7. Lin Q. Dent Mater. Sun L. Biomaterials. of restorations in a general dental practice. J Dent Res. Chow LC. Stupp SI. Takagi S. Wang M. Weir MD. Okada F.11(6):5199–206. et al. Tagami J. J Dent Res. Moreau JL. Xu HH. Newcomb CJ. enamel-like hierarchical nanostructures on single 2007. Otsuki M. Takagi S. Ma G. Prim Dent 2010. Snead of calcium phosphate nanoparticles on Ca-PO4 com- ML. Weir MD.9(1):31–6.89(1):19–28. Strength and 90. 2011. Huang Z. 2010. 2008. Update on dental nanocomposites. Growth and mechanisms of phosphate particle size and silanization. 95. Chow LC. Nanocomposite for rapid tooth repair. Sun L. J Dent fluoride release characteristics of a calcium fluoride Res. An audit on the placement and replacement PO(4). Xu HH. 2010. Sun L. Materials chemistry: a synthetic enamel 92. enamel-like hydroxyapatite through solution mediated 93. Zhang J. Chow LC. Xu HH. Xu HH. release. Suzuki T. Effects 89.433(7028):819. 2010. Dent Mater. Sun L. Nanocomposites with Ca solid-state conversion.29(32): 91.31(35):9202–11. Biomaterials. Care. 2007. Sun L. Bringas Jr P. Strong nanocomposites with Ca. Liu XY. Chen MH. Moreau JL. Chow LC. crystalline hydroxyapatite micro-ribbons.89(6):549–60. 2011.

usually beginning with the demineral- ization of enamel and followed by bacterial inva. Xuedong (ed. Li (*) State Key Laboratory of Oral Diseases.3 Percussion suspected sites. The interproximal marginal ridge Caries does not cause periodontal and periapical area has ink stain discoloration under the enamel inflammation. dental radiographs or other special inspec. It can also be used to assess e-mail: 43339426@qq. Periapical © Springer-Verlag Berlin Heidelberg 2016 85 Z. extension of cavity can be examined.1). Zhang Yaru. the depth and cases. The Diagnosis for Caries 5 Yang Liu. we caries is defined as a localized and progressive can get a general scope of carious damage. For some difficult areas. People’s Republic of China secondary caries [1].1.com the proximity of caries to pulp chamber. 5.2 Probing sion. Wang Shuang. It usually takes 6–12 months for caries to appear.1007/978-3-662-47450-1_5 . Chengdu. Yaru • P. Shuang • Z. Generally.1 Inspection When making an examination for dental caries on 5. mal cavity is suspected and cannot be located nosis (Table 5. cal areas. For observation on tooth cervi. bacterial infection that results in disintegration of the tooth. The sharp probe is used to inspect the suspicious sis with routine inspection. through an inspection. we can make a correct diagno.). so the reaction to percussion is or a visible cavity. we can find black or chalky area or a formed cavity.2. Pulp exposure can also be located while examining the deep carious lesion.1 Radiographic Examination Y.1.1 Conventional Diagnosis tooth surface to locate the area of dentinal hyper- Methods sensitivity. Liu • L. 5. Li Boer. and Peng Li According to the glossary of endodontic terms. the cheek and tongue should be pulled away to fully expose buccal and lingual surface of 5. DOI 10. Depending on the inspection. Boer • W. Dental Caries: Principles and Management. Radiographic examination can be helpful in locat- West China Hospital of Stomatology. the probe is useful to locate affected area when it is hooked by the edge of the cavity. If a proxi- tions are supplementary methods for caries diag.1. The probe can also be used on the 5. always negative.2 Special Diagnostic Methods 5. With the help of the probe. posterior teeth. ing proximal caries and undermining caries and Sichuan University.

removal of stimuli. it is . tory. The pulp is sup- guished from normal triangular low-density areas posed to be healthy if pain disappears right after in the cervical region of the tooth. the practitioner can obtain well a vision on hidden carious lesion The new technology of caries Fiber-optic transillumination This system uses fiber transillumination diagnosis for potential caries diagnosis Electrical impedance technology This technology is an alternative way for occlusal pit and fissure caries diagnosis Ultrasonic technique It is a new method for caries detection by measuring the wave that reflects back from tooth structure Elastomeric separating modulus Elastomeric separating modules are used technique to separate apart adjacent tooth temporarily for examination of proximal surfaces Staining technique This technique can show the presence of caries and estimate the depth of carious lesion Quantitative laser fluorescence Autofluorescence is light emission technique phenomenon of biological structure The differential diagnosis of the Enamel hypocalcification The key points of the differential superficial caries Enamel hypoplasia diagnosis for caries are glossiness and Dental fluorosis smoothness. But if the pain is lingering.1 The diagnosis for caries Conventional diagnosis methods Inspection Black or chalky area or a formed cavity can be seen Probing Probe can be used to locate affected area. A series of researches have irritation is examined during cold and hot revealed that more than half of proximal caries are irritation test. Radiolucency on hard tissue due to demineralization is identified as The response of dental pulp toward cold and hot carious lesion. Secondary car.2 Cold and Hot Irritation Test clinical assessment of caries. the area of dentinal hypersensitivity. Table 5. symmetry of the lesion. Liu et al. When cold water is used as stimulus. and the should be analyzed and combined with clinical patient’s response is evaluated. and pulp exposure Percussion The reaction to percussion is always negative Special diagnostic methods Radiographic examination Radiolucency on hard tissue due to demineralization is identified as carious lesion Cold and hot irritation test The response of dental pulp toward cold and hot irritation can determine the severity of caries Dental floss examination Dental floss can diagnose caries on proximal contact area Diagnostic cavity preparation After removing supportless enamel. Proximal caries should be distin. stimuli can elicit acute pain. Examination is done by putting seen on the radiograph. the diagnosis result percha stick on the surface of the tooth.2. predilection site. Since the radiograph is a chloroethane-soaked cotton ball or hot gutta- two-dimensional image. and progress of the lesion and bite-wing radiographs are commonly used for 5.86 Y. These external examination. the pulp is likely to be in irreversible inflamma- ing materials on the floor of the cavity. ies should be differentiated from low-density bas.

3 Dental Floss Examination A new diagnostic technique for caries was Caries on proximal contact area is difficult to be called fiber-optic transillumination. The floss will be torn if caries is present. The carious cavity is tioner can obtain well a vision on hidden carious filled with dead and decayed tissue. Dental uses fiber transillumination for potential caries floss can be used as a convenient method. sensitive. The normal tooth surface of the tooth. This ultrasonic and X-ray examination. 5. Generally. sue. saliva.3. reflecting waves. The principle is based on the putting a dental floss across the embrasure of fact that the light transillumination index in the suspicious tooth surface and moving the decayed tissue is lower than that in normal tis- floss horizontally in a seesaw motion. These wave was used for caries diagnosis.1 Fiber-Optic Transillumination. some techniques and meth. At sensitivity of caries diagnosis.2. However. .3. With the latest development in sci. progressive.4 Diagnostic Cavity Preparation The electrical impedance technology is an alter- native way for caries diagnosis by examining After removing supportless enamel. last.5 The Diagnosis for Caries 87 important to note that the flow of water may methods have greatly improved the accuracy and affect the accurate location of carious cavity. the tooth decay area and occlusal fissure. it is difficult to wave is received by a sensor when reflecting back identify early caries which is in the hidden area from the tooth surface. The typical pathological changes have important reference value for caries diagno. the methods for dental caries ies detection by measuring the wave that reflects diagnosis are mainly based on clinical inspection back from the tooth structure. shape. Examination with floss can be misled by dental calculus. After that. Dying the Following this principle. tooth potential difference. the practi. The conductivity is measured by probe in tious dentin.2 Electrical Impedance Technology 5. and current passes through the pulp condition can be easily defined. drying. The electric caries detector device measures 5. Tooth caries is chronic.3 Ultrasonic Technique hard tissue. The ultrasonic technique is a new method for car- sis.5 % basic fuchsin can the tooth surface is measured under controlled help dentists to identify and remove the infec. the decayed area shows dark iner can experience the roughness of the sur. and sta- ble for occlusal caries detection. This system examined by inspection and probing. 3].2. caries should be differentiated from dentin hypersensitivity. Currently. cavity should be removed completely. face. 5. electrolytes. pulp to the ground through handheld lead form- ing a circuit. FOTI 5. By diagnosis [2. the exam. shadow. At present. and the decay one are supposed to have different ence and technology. To identify the scope and depth of cavity. Therefore. 18 MHz frequency ods are being used for caries diagnosis. and bacterial diseases. the resistance offered by decalcified dentin with 0. and quality of tooth 5. and lesion. this area becomes more the infectious dentin on the floor and wall of the electric conductive than the normal tissue. The main characters of tooth caries are the changes in color.3. This method is simple.3 The New Technology the bulk electric resistance and potential differ- of Caries Diagnosis ence.

7].5 Staining Technique Enamel hypoplasia is a deficit in enamel forma- tion. For this reason. In mild 5. 5. the diag. Liu et al. coloration [9] (Fig.4 Elastomeric Separating 5. tiny white streaks or specks are Fluorescence Technique seen in the enamel. 5. 5. the dye is used in carious cavity to stain dead and decayed dental tissue. and cervical part are caries’ predilection done based upon its location. Dental fluorosis is a developmental disturbance. This reflected light is detected by spectrum for Caries and recorded in computer and demineralization is quantified. However.4.3.88 Y. smoothness. However. helpful especially when proximal surface caries was examined.6 Quantitative Laser type of fluorosis.4. the scope [6. characterized by irregular. areas like cusps or any other smooth surface.1a). The enamel surface 5. This method can be spots or plaque on tooth surface [8] (Fig. The lesion is rate apart adjacent tooth temporarily for exami. It could hardly be found on the self-cleaning nosis of the smooth surface caries is more chal. Quantitative laser fluorescence devices use high-intensity halogen lamp to stimulate the 5.4 The Differential Diagnosis can also be rough in appearance. opaque. 5]. proximal sur- The diagnosis of the pit and fissure caries can be face.1c). 5.4 The Key Points tooth to emit the fluorescence in green spectrum of the Differential Diagnosis [4. Common clinical developmental disturbance is caused by abnor- presentation of caries is described below. The com- monly used dye is 1 % basic fuchsin. and chalky nation of proximal surfaces. The autofluorescence of [11] (Fig. sites. and confocal laser scanning micro. light lesions that are caused by developmental distur- scattering. The related other new technologies are dye-enhanced laser fluorescence (DELF). and hardness are not affected.4. glossiness.1 Enamel Hypocalcification Modulus Technique This is a condition where the enamel is formed Elastomeric separating modules are used to sepa. the dentist can determine the presence of caries and 5. The lenging due to its appearances. The enamel is thin and deficient in amount. without adequate mineralization. yellowish.1b). The caries teeth have chalky or snuff colored spots without gloss.3. but discolored and pitted in severe type [10]. mal development or irregular mineralization on . due to exposure of tooth bud to high concentra- tion of fluoride during its development. dental tissue decreases in demineralization of the tissue.3 Dental Fluorosis estimate the depth of carious lesion.2 Enamel Hypoplasia 5. bance may have color changes. of the Superficial Caries Predilection Site Pit and fissure. Glossiness and Smoothness The enamel quantitative light-induced fluorescence.4. 5. The staining technique usually stains the degraded It is seen clinically as dot or banded sunken collagen which is present in the carious cavity but defects with chalky.3. With this technique. The spots and stains left by fluo- Autofluorescence is light emission phenomenon rosis are permanent and may darken over time of biological structure. or brownish dis- never stains the intact collagen.

Caries Res. Fluorescence methods (VistaCam iX proof and tions. 4. and reproducibility of direct lesion which is chalky white in appearance can visual examination following tooth separation for the be arrested by the tooth remineralization. 5. acid. (c) White specks central incisors.19(4):379–84. and cold stimula. et al. It will neither uation of effect of developer age in the detection of develop nor disappear. developmental lesion can be found bilaterally and in a similar manner. This is different from dentinal ous lesions in teeth recovered from archaeological con- hypersensitivity. fibre-optic transillumination. The dentin hypersensitivity is text [J]. Zalewska M. Madalli VB. sensitive to sweet. Tomczyk J. diagnosed as dental hypocalcification. shooting pain. Wenzel A. The initial enamel bite-wing radiography. Progress of the Lesion The lesions of develop- References mental origin will become quiescent as soon as 1. 2014. or disturbances affect the tooth during the period of tooth with exposed root surface. 1998. . It is known as enamel hypoplasia. 2014.5 The Diagnosis for Caries 89 a b c Fig. visual examination. areas. Caries Res. This sensitivity can also Symmetry of the Lesion The developmental be found on wear-away tooth. decayed tooth. Am J Phys Anthropol. 1985. heat. development. 2. J Clin Diagn Res. Danielsen B. Basavaraddi SM.1 Different clinical images of tooth diseases. The use of fibre-optic transillumi- The Differential Diagnosis of the Medium nation in the diagnosis of posterior approximal caries Caries The teeth with medium size caries are in clinical trials [J]. and ress toward the pulp chamber. are seen on the labial surface of maxillary anterior teeth the tooth surface. The color of carious lesion changes an in-vitro study [J].8(3):236. Hintze H.154(4):525–34. The caries is progressive approximal caries using three speed dental x-ray films: by its nature. 3. (b) The yellow circle shows sunken defect with yellow discol- (a) Chalky plaques can be seen on the labial surface of the oration.32(3):204–9. Based on the stage of tooth stimulation of nerve endings in dentinal tubule development. The eval- the tooth erupts in the oral cavity. et al. Therefore. The sensation can range all the way from irritation to intense. Mitropoulos CM. Annigeri RG. Reliability of from chalky white to dark brown with its prog. the lesion can be seen on different due to change of temperature or pH in oral cavity. Komarnitki J. Patients usually complain that they feel pain DIAGNODent pen) for the detection of occlusal cari- with these stimuli. identification of cavitated carious lesions in contacting approximal surfaces [J].

fluorescence system for in vivo diagnosis of occlusal 10. 1938. Dean HT. J Dent Res. Rushton MA. Kidd EAM.58(6): Comparison between visual examination and a laser 441–52. enamel hypocalcification [J]. Comparison of laser fluorescence and longitudi. ASDC J Dent Child. 2014. Hafström-Björkman U. 2001. conventional excavation [J]. Seow WK. 5. 1962. .26(4):241–7.35(6):421–6.90 Y. Josselin D. 9. Sundström F. MicroCT-based compari.27(1):12. 1990.112: nal microradiography for quantitative assessment of 24–7. 1992. Manji F. Fejerskov O. tion: a review [J]. caries [J]. Am J Dent. Kaisarly D. Liu et al. Lai G.69:692–700. 11. et al. Xu X. Endemic fluorosis and its relation to dental caries [J]. et al. Enamel hypoplasia in the primary denti- 6. Brailsford SR. Caries Res. The surface of the enamel in hereditary E. Caries Res. Br Dent J. Sheehy EC.53(33):1443–52. in vitro enamel caries [J]. 7. de Jong 8. The nature and son between fluorescence-aided caries excavation and mechanisms of dental fluorosis in man [J]. et al. discussion 721. 1990. Public Health Rep. Baelum V.

planning traditional curative interven- European Union spent a total of €54 billion on tion strategies entirely on the basis of epidemiologi- oral health care. This fact should be interpreted on the back- Oral diseases. Xiao Department of Preventive Dentistry.5 billion [2].1. China a time of dramatic decline of caries status e-mail: hongxiao@scu. underpins that restorative treatment is unaffordable income countries. an important determinant of restorative care. This trend can be attributed to © Springer-Verlag Berlin Heidelberg 2016 91 Z.1. In the recent several decades.000 Not surprisingly. the costs of in low-income countries [5.1007/978-3-662-47450-1_6 .to 14-year-old 5–10 % of public health spending is used for oral children by 30 %! health care [1]. 2004 expenditures for oral health care were US$ and political conditions is doomed to fail. for low-income countries. For example. a compre- nature.and middle. gross domestic product (GDP) below US$ 5.to variety of oral diseases. Back in the year 2000. have been ranked the fourth most expen. ity and disability among the 0. 4]. which further fordable financial resources from low. Dental Caries: Disease Burden Versus Its Prevention 6 Hong Xiao 6.). However. Sichuan University.2 Uneven Distribution of Oral Disease Burden Around the World H. treatment to control periodontal diseases in chil- dren on basis of the Community Periodontal Index (CPI) of Treatment Needs (CPITN) data greatly 6. 6].1 Global Trends of Caries exceeded the total national health-care budget of Burden Kenya [3. it appears that no country with a important source of oral disease burden. Take Nepal as another example: the total costs of restoring dental caries cavities of the 6. hensive national essential health-care package at sive disease to treat in most industrialized coun.cn worldwide. If we formed under the medical umbrella. economic. the However. the cal data without considering the social. In the high-income industrialized countries. In partic- 81. Among the take the Care Index (F⁄DMFT*100 %) for 34. such figures did not ular the national economic conditions appear to be include the additional costs of dental care per. DOI 10. a cost of US$ 4 will reduce the burden of mortal- tries. has a Care Index higher than 30 %. these costs will require unaf. Dental Caries: Principles and Management. Xuedong (ed.1 Oral Diseases: One of the Most child population would exceed the total health- Costly Diseases to Treat care budget for children of the entire country [5]. we have witnessed West China Hospital of Stomatology. and in the United States.edu. dental caries has long 44-year-olds as an indicator of the country’s restor- been the main factor attributable as the most ative care level. despite their non-life-threatening ground that. Chengdu.

the preva- disease burdens mainly because of communica. caries status can be monitored through 6. noncommunicable diseases are the main consumption of sugar and inadequate use of source of disease burden [7]. should be coordinated more effectively with other fifth of the caries lesions in the primary dentition programs in public health [8–10]: were treated. This might be attributed to increased tries. However. middle-. ranging from countries and some countries of Latin America as low as 46. the middle-income countries had about 20 %. However.92 H. Such proportion of treatment dra- matically decreased to about 5 % in the middle.8 % in Latin America and Caribbean. Xiao widespread use of topical fluoride and increasing Situations in the permanent dentition told a awareness of the importance of maintaining good better story. This result from a number of public million population of each country with the health measures including effective use of fluo- worldwide average of 1. Most industrialized a half of most countries or regions. disease contribution to the total YLD/million Worldwide. Worst findings were found in incorporated as appropriate into policies for the low-income countries. contribution of caries was found to be over the mean DMFT index. recent years. However unfortunately. China is found to be among those among adults is high as the disease affects nearly countries with lowest oral disease contributions. ease affecting children and adults. as measured by world. where the proportion the integrated prevention and treatment of of treated caries lesions could be totally neglected. chronic noncommunicable and communicable . dental caries still remains a common dis. and essential to general health and that oral health tion especially from a professional perspective. lence rates of dental caries seem to increase in ble diseases. it Programme emphasizes that oral health is integral is able to reveal some valuable objective informa. only about one.6 %. is a determinant factor for quality of life. posing tre. 6. missing. fluoride. they ferent story. in some parts of the Care Index (F/DMF score) of over 50 %.1 can be found in sub-Saharan Africa closely fol. However. However. Both the countries carry heavy of dental caries were low. and improved self-care practices. periodontal diseases.3 Developing Global Policies national epidemiological surveys by recording the Highlighting the Importance dmf/DMF indices (decayed. in the high-income coun. 100 % of the population in the majority of coun- With respect to relative contribution of caries tries. the levels lowed by India. countries to as high as 89. Although the recording of such indices disregards the impact of perceived The policy of the WHO Global Oral Health pain and discomfort as a result of dental caries. including car. A steady decline of caries experience make very little contribution to the total YLD/ is found. If the burden of disease is described using The temporal trends in dental caries experi- years lived with disability (YLD) per million ence of 12-year-old children in developing and people. • To adopt measures to ensure that oral health is income countries. the Care Index was found mendous economic burden.1. and edentulism. in high-income countries.3 illustrates the levels of dental to oral disease burden of different regions of the caries among 35–44-year-olds.2. and 6. while world. In most developing countries. and filled of Oral Health tooth/surface indices).7 % in established economy market show high DMFT values. The WHO The proportion of each component varies greatly Global Oral Health Programme has implied that among high-. Figure 6. When it comes to oral diseases. to be within 5 % for the low-income countries. Usually. together with changing living conditions. the highest disease burden of the world developed countries can be illustrated in Figs. While the Middle rides. the prevalence of dental caries population. Eastern Crescent is found to have the highest oral lifestyles. greater emphasis is put on developing global poli- Data collected between 1990 and 2004 indicate cies based on common risk factors and approaches that. and low-income countries. the industrialized countries tell a dif- ies. The high-income countries had a oral hygiene.

6 Dental Caries: Disease Burden Versus Its Prevention 93 Decayed missing and filled permanent teeth Very low: <1. to (Reproduced. and to provide diseases and into maternal and child health affordable fluoride toothpaste policies • To develop and implement the promotion of • To take measures to ensure that evidence.who. 6. Petersen et al. of fluoridation programs. and filled teeth (DMFT) index) among levels of fluoride. with the permission of the publisher.6 Moderate: 2.int/bulletin/volumes/83/9/petersen- (Reproduced. and which have not yet estab- 12-year-olds in developed and developing countries lished systematic fluoridation programs. from 0905abstract/en/) 5 • To consider mechanisms to provide coverage of the population with essential oral health 4 care.1 Dental caries levels (decayed. in drinking water. from consider the development and implementation Bulletin of the World Health Organization. missing. nurses. http://www. teeth (DMFT) index) among 12-year-olds worldwide [7]. salt. and filled Bulletin of the World Health Organization. 6. . oral health and prevention of oral disease for based approaches are used to incorporate oral preschool and school children as part of activ- health into national policies as appropriate for ities in health-promoting schools integrated prevention and control of noncom.2–2. http://www. giving priority to [7]. to incorporate oral health in the frame- work of enhanced primary health care for 3 DMFT chronic noncommunicable diseases. missing.int/bulletin/volumes/83/9/petersen- 0905abstract/en/) equitable strategies such as the automatic administration of fluoride.2 Changing levels of dental caries experience (decayed.2> Low: 1. • To scale up capacity to produce oral health municable diseases personnel. including dental hygienists. or milk. in collaboration with 1981 1983 1985 1987 1989 1991 1993 1995 1997 1982 1984 1986 1988 1990 1992 1994 1996 1998 integrated programs for the prevention of Developed countries All countries Developing countries chronic noncommunicable diseases • For those countries without access to optimal Fig. Petersen et al. for example. and to 2 promote the availability of oral health services that should be directed toward disease preven- 1 tion and health promotion for poor and disad- 0 vantaged populations.7–4.4 High: >4. with the permission of the publisher.who.4 No date available Fig.

covering 5–74-year-olds from 11 provinces.9 High: >13. The second national epidemiological investiga- sions dedicated to the prevention and control of tion of oral health in China took place from 1995 to oral and craniofacial diseases and conditions 1998. The first national epidemiological investi- • To address human resources and workforce gation of oral health in China is the first planning for oral health as part of every large-scale epidemiological investigation orga- national plan for health nized since the establishment of P. http://www. China. and municipalities maximize resources in support of national oral directly under the central government.340 students exam- experience of community oral health programs ined. prevention in order to consolidate and adapt oral autonomous administration regions. auton- sibility among stakeholders in order to omous administration regions.2 Caries Burden in China bution of these auxiliaries to the primary-care level and ensuring proper service back-up by 6.2. palities directly under the central government. which had examined the • To strengthen oral health research and use evi. This investigation had included 6 age groups • To strengthen partnerships and shared respon. and munici- health programs and to encourage the inter. from 0905abstract/en/) and auxiliaries.0 Low: 5. 6.0–13. the budgetary provi.94 H. missing.9 Moderate: 9. • To increase. providing for equitable distri. country exchange of reliable knowledge and There were altogether 131. 6. . status of caries and periodontal diseases in pri- dence-based oral health promotion and disease mary and middle school students of 29 provinces.int/bulletin/volumes/83/9/petersen- (Reproduced.712 people at 396 sample sites were selected. A total of health programs 140. China has organized two nationwide epidemiol- tional standards and to evaluate progress in ogy investigations.0–8.R. of Oral Health in China tem into health surveillance plans so that oral health objectives are in keeping with interna.1 The First and Second National dentists through appropriate referral systems Epidemiological Investigation • To incorporate an oral health information sys.3 Dental caries levels (decayed. The first was conducted promoting oral health between 1982 and 1984. Xiao Decayed missing and filled permanent teeth Very low: <5. and filled Bulletin of the World Health Organization. with the permission of the publisher. teeth (DMFT) index) among 35–44-year-olds worldwide [7].who. Petersen et al. as appropriate.9 No data available Fig.

Unfortunately.2. overall status of oral health in China. No difference is observed between urban accounting for 11. Caries prevalence rate of the 12-year-olds is while most of these children have a DMFT of 2. 32.0 % in the primary dentition. Analysis of the frequency first molars. and 65–74-year-olds were 76.9 %.8 % of all attention when it is found that 79. caries prevalence rates for 5-year-olds. 35–44-year- olds.1 % of the total subsample. 6. and boys have a statistically sig- The constitution of DMFT indices can be viewed nificant lower caries prevalence rate than girls in Fig.0 %).7 Missing 0. The most common rea- Caries status obtained from stratified popula.1 Caries Status of 5-Year-Olds examine the main reasons for caries in children.45 % of 12-year-olds have pit and fissure .5).8 %.2. which has shown that an astonishing (25. A total of 93. toothbrush- live in the cities have a slightly lower caries prev. and the remaining vast level randomized sampling [11]. Children who sugar consumption before sleeping. It has been At the planning period.8 63.0 %. the sampling methods found that 13 % children began to brush their have been carefully designed as stratified multi. 88. and planned future human resource allocation in oral health service. Approximately half of the subsample have The third national epidemiological investigation their guardians (mostly parents and grandpar- of oral health in China was implemented in 2005. carious teeth have not been treated (Fig.6 %). 6. people were selected covering 5–74-year-olds in Around one-fifth of children don’t brush their 6 age groups.2 The Third National Epidemiological Investigation examined children. correlate with caries status of children. 28. and filled teeth in 5-year-olds in China (%) 6. missing. Fig. and 39 % of 5-year-olds use the fluori- tionnaire investigation was simultaneously con. The 5-year-olds have a caries prevalence rate of It has been found that urban/rural distribution. a comprehensive ques.4 Constitution of decayed. sons for dental visits are acute or chronic tooth- tions is detailed as follows.2 %). and oral hygiene by parents all alence rate (62.7 %).5.6 Dental Caries: Disease Burden Versus Its Prevention 95 Results of these two epidemiology investiga- tions have provided valuable first-hand data for the central government to make oral health- related policies. ache and other reasons such as dental emergency. The sample well represents the teeth.5 Filled 2. 6. 1. ents) completed the questionnaire. 66. In addition There were 49 % parents aware of the fluoride to dental examinations.3 % of all cari. teeth before the age of 3.2 Caries Status of 12-Year-Olds Average DMFT of the 5-year-olds is 3. According to the second national survey which was conducted in 1995.2. visit dentists periodically. children have a higher caries prevalence rate (70. and mandibu- distribution of DMFT in children has aroused our lar second molars. while in the rural areas. respectively.33.4 % vs.8 %. It ducted to investigate the oral health-related should be paid attention to that only 22 % children concepts and behaviors of the selected sample. and 64. and rural areas. proportion of carious teeth have never been The most often affected teeth are mandibular treated (96.2. 6.6 %.826 majority has just begun to brush their teeth. ing starting age. toothpaste. maxillary first molars. 12-year-olds. who present a significant car- of Oral Health in China ies index of 8.4. Multiple regression analysis was performed to 6. 45. set up targets for oral health ser- vice. dated toothpaste when brushing their teeth.2. Decayed 96. In ous teeth concentrate in about one-third of the China.

subsample have never seen a dentist. 99 % do not use dental floss. However. to be smokers. only However. 6.1 %).8 Missing 0.5 Constitution of decayed. It is sad that only 28 % have urban area and rural area (2.9 %).3 Caries Status group is the most important age group. nificant higher caries prevalence rate than men Ninety-three percent of the children report that (91.96 H. in have visited a dentist. investigated brush their teeth daily. Not tal visits and self-perceived impact of oral health. Better teeth brushing the percentage of daily consumption of cigarette habits are found in cities.6 Filled 8. However. The most Among the 35–44-year-olds. signifying bad periodontal status. dissert. 84. over 60 % of them have realized There are 32 % questionnaire respondents reported that bleeding during toothbrushing is abnormal.75 % vs. The investigated 12-year-olds have completed the questionnaire by themselves. much difference was found between the urban It has been found that 82 % of the 12-year-olds and rural populations (89. The percentage DMFT indices is shown in Fig. In addition to questions on age group for adults. and 35 % have reported to be brushing their dren smoke (boys 5. .1 %. 87.7 %).7 % and girls 0.6 Filled 10. such All of the investigated subgroup answered the as sweetened milk. women than in rural and alcohol is further reduced to 1.3 % vs. Sixty-nine percent of the children have (32. The constitution of the they have never used dental floss. Xiao Decayed 88. However. missing. unfortunately. There is a huge gender difference in In the past 12 months.2.6 Fig. On a daily basis.5 %) and that teeth at least twice a day.0 Missing 57. daily consumption of sugar-containing food.19 %). while 23 % men. areas and men. 69 % believe common reasons for their dental visit are acute or there is a need for them to receive oral treatment. 27 % use toothpicks. candy.0 % and 0. carbonated soft questionnaire. for boys and girls.1 % vs. has been affected by caries. respectively. and there is a huge difference between chronic toothache.6.6 Constitution of decayed. missing. but over With regard to oral health-related knowledge. formed the habit of frequent dental check-ups. of sugar is found in 21 % of those investigated.1 %). eases. the vast majority of this age group (88. women are found with statistically sig- 28 % of them brush their teeth at least twice a day.2. 6. the of children who use fluoridated toothpaste is prevalence rate for root caries is near one-third 46 %. quite questionnaire has also included questions on den. 6. As this age 6. It has been found that the oral health-related knowledge and behavior.4 Decayed 34. and filled teeth in 12-year-olds in China (%) teeth in 35–44-year-olds in China (%) sealants. 0. however. and sweetened fruit juice. 47 % of the total contrast to 2 % women. 21 % of 12-year-olds daily alcohol consumption. Fluoridated tooth- only one-tenth of 12-year-olds understand dental paste is used in 46 % people. It is satisfactory 89 % have reported that they brush their teeth that only a small fraction of the investigated chil. drink alcohol daily. daily. Daily consumption plaque as the cause for caries and periodontal dis. it has of 35–44-Year-Olds been receiving continuous attention from the The 35–44-year-olds is the WHO recommended central government. Among all the 35–44-year-olds. and filled Fig. drink.

It has been found that dental check-ups.1 Filled 1. three-quarters of the questionnaire respondents Multiple regression analysis has revealed that brush their teeth on a daily basis and that slightly the caries status of the 35–44-year-olds is closely over one-quarter brush their teeth twice a day.0 %). however. there are urban population (60. and About half of the examined subjects have few of them have formed the habit of regular handed in the questionnaire. the majority of them have attributed their as low as 1. 6. the respondents have ever used dental floss.4 Caries Status found in 27 % questionnaire respondents. The age group of significantly higher in urban populations than 65–74-year-olds are found to be heavily affected rural (73 % vs. For the remaining males (61.3 %). with percentage is found to be higher in cities than in daily consumption of sugar-containing foods. the percentage of genders. missing. Daily sugar-containing food consumption is 6. and Caries prevalence in the age group of 65–74-year.6 % respondents.9 Fig. 65 %). Rural population have a root months. treated (1.9 % of all the carious lesions in the dental attendance to be because of acute or root have been treated (Fig. even at this age.8 Missing 75. toothbrush. only 16 % of them have been to a den. the Those with no use of fluoridated toothpaste.4 %.9 Decayed 22. majority of which is missing due to caries Over half of the elder population believe they (75. The mean DMFT score is 14.3 Filled 1. but almost none of basis manifest with high caries risk. And it is found that among those who is as high as 98. in the past 12 by caries in the root. cities and females. Quite surprisingly. Also. caries prevalence rate of 67. However.7). self-oral hygiene behavior is found to be better in sumption of sugar-containing foods. There are 26 % of the respondents who and who are not brushing their teeth on a daily report they use toothpick daily.2. chronic toothache or other dental situations. Alcohol consumption is not much difference is discovered between both found in 13. 6. An of 65–74-Year-Olds average of 27 % of the respondent smoke. the male is almost six times that of the female. and only a fraction of the iceberg is are in need of oral examination and treatment.1 % as many as 46 % 35–44-year-olds who have females are affected by root caries. 6.6 Dental Caries: Disease Burden Versus Its Prevention 97 Decayed 98.1 %). In 27 % of the questionnaire ing frequencies. rural areas.9 %) (Fig. It is found that 66. fluoridated toothpaste is used. higher than the tist. there is a huge difference between the two gen- olds is found to be very high.2 %. more than 20 years. respondents.8 Constitution of decayed and filled root caries in Fig. and filled 65–74-year-olds in China (%) teeth in 65–74-year-olds in China (%) Root caries is another important issue that and the percentage is found to be statistically should not be neglected. and not much difference is smoke.2. It is further discovered that only 54 %.8).7 Constitution of decayed.7. The prevalence rate ders. This related to the use of fluoride toothpaste. 90 % of them have been smoking for found between urban and rural populations. higher than never visited a dentist ever. and other behavioral variables. con. 6. only 19 % of the respondents report that .

tively [15]. the invention of X-ray has require removal of any or all of these contributing offered another possibility to visualize lesions factors. either of dentinal lesions were found to be ranging with propaganda via mass media or face-to-face between 0. and the major. Usually manuals expenditure on dental visits.3 Caries Preventive Strategies 6.3. Each referral is acute and chronic toothache. Given time. it is unfortunate that about one-third of the all the there will be dental health educational and pro- respondents have never been to a dentist for any motional activities held across the country. sensitivity and specificity as well as operator ars and frequent dental visits. Later. themselves who can only resort to their naked duce the chronic oral disease which brings pain eyes and self-practicing experiences. appear to have very low sensitivity and high specificity in diagnosing caries [12–14]. 6. Self-awareness with regard to car. Removal of etiological factors is very impor- dents have experienced toothache.3. 6.1. so that they will be self. agreement. 83 % of the respon. A conclusion from one study was that conscious about the importance of keeping good although good results were obtained regarding oral hygiene. There form of oral examination or treatment. have been made. not uted free of charge. are dental schools or colleges. China. Table 6.85 and 0. There is a hierarchy of caries-preventive strat- egies which include the following. Secondary prevention mainly refers to the early tors. free dental check- When we analyze the oral health impact on ups are available. Xiao they have visited a dentist within the past 12 education. such as visual 6.1 Conventional Caries Detection Methods Traditional diagnostic methods. caries ceptible teeth. Therefore. preventive methods that are to be introduced in the following section. However. The most common reason for dental own national campaign for over a decade. In many cities where there to be able to find a source to partly cover the bill. still at their early stages.98 H. respec- educational lectures.2 Secondary Prevention Dental caries results from a variety of contribut- ing factors. new caries scoring system as presented in ies prevention is often highlighted in this stage.2. Ekstrand et al have proposed a logical factors.3. restricting the consumption of sug.92 and 0. for another . carbohydrate-rich diet. Primary prevention is the most important strategy Continuous attempts to improve the sensitivity as it stresses and deals with combating the etio.97 and 0. and other hygiene conditions. There are three most important fac. use of fluoride. it is sad to find that over half the respon. tant in this stage. year on the “love teeth day” on September 20th. namely. and sus. This has and discomfort to the majority of the population resulted in countless mistaken diagnosis and worldwide since an early age.1 Primary Prevention inspection. that hide from usual visual examination. Many countries have set up their own launches Although improvements in visual inspection with or campaigns to deliver the concept of oral health new scoring systems (take. the interrelation and diagnosis mainly relies heavily on the dentists interaction between these three factors will pro. cariogenic microflora (termed as diagnosis and treatment of lesions found to be dental plaque). effec. for example. omission of countless lesions which had been left tive caries-preventive strategies almost always not dealt with. The main methods include den- ity of the elders are not satisfied with their oral tal plaque control. it takes more time to learn the method. For a long time. containing educational information are distrib- dents report that they are fully self-financed. ICDAS. daily life.93. has launched its months. Sensitivity and specificity for detection People are motivated by a variety of means. For the is a unique theme every year.

2. It can be either reflected. carious lesions is now a reality. the sensitivity of uated in a few studies. 6. caries can not only be detected detection on both occlusal and approximal sur. This quantitative method. transmitted.1 Detailed criteria for visual inspection of 1970s. scattered.6. digitized fiber- contact with an infected fissure [16]. It brings special advantages in diagnosing occlusal surfaces introduced by Ekstrand et al caries in the proximal surfaces which are difficult Classification Visual inspection to discover with the naked eye under normal 0 No or slight change in enamel means of illumination. and the initial results the explorer is reported to be only about 0. many new and high-tech diagnosing has a long history and is still the most widely technologies have become available. Moreover. Bitewing radiography new possibilities in caries diagnosis at its earliest has been found to be useful for dentinal caries stages.6 Dental Caries: Disease Burden Versus Its Prevention 99 Table 6. the site of a superficial carious lesion. in a the occlusal view during transillumination) study on intraoral transmission of pathogenic through computer image analysis.3. providing used diagnostic technique. occlusal lesion depth.2. that a combination of FOTI and The use of explorers has received some dis. The sur- visible after air drying face is examined using the transmitted light.3 New Caries Detection Methods The use of film radiograph for caries detection Till now. and good specificity. indicate that both the sensitivity and specificity A number of reports have demonstrated that are very high. or absorbed. ing accuracy while tends to damage tooth tissue Using the digital image of a tooth (seen from and contaminate sound areas. Therefore. but also can be quantified. The different sionals [17–20]. However. this method needs to be probing with a sharp explorer may cause damage developed further before it can be applied in clin- to newly erupted teeth or even create a cavity at ical situations. visual inspection was useful for determination of pute as some believe it cannot increase diagnos. For detec. showed that sterile fissures have attempted to improve the performance of might be inoculated by probing after previous FOTI. in vitro study. used caries detection adjunctive to dental profes.3. seen 2 Opacity or discoloration distinctly from the occlusal view. Cortes et al showed. The contrast between sound and carious tis- 4 Cavitation in opaque or discolored sue is then used for detection of lesions. its use has been questioned by several authors. In FOTI. it has no value for occlusal tant implications as thanks to these high technol- enamel caries detection and only a limited value ogies. longitudinal quantitative monitoring of for approximal enamel caries detection. Loesche et al. Its use can be traced back to the phenomena can occur alone or in combination. Demineralized areas appear opaque or discolored enamel and/or grayish discoloration from the darker compared with the surrounding sound tis- underlying dentin sue. enamel exposing the dentin FOTI has been evaluated in a number of stud- ies for detection of posterior approximal carious lesions and has shown low-to-good sensitivity example) seem promising. . white light from translucency after prolonged air a cold-light source is passed through a fiber to an drying (>5 s) 1 Opacity or discoloration hardly intraoral fiber-optic light probe that is placed on visible on wet surface but distinctly the buccal or lingual side of the tooth. optic transillumination (DI-FOTI). researchers microorganisms. has been eval- tion of occlusal dentinal lesions. Decayed tooth structure visible without air drying manifests itself as the dark shadow under illumi- 3 Localized enamel breakdown in nation of ultraviolet. However. 6. in an tion is still needed. further clinical valida.5–0.2 Fiber-Optic Transillumination New Caries Detection Methods: Optically (FOTI) Based Light interacts with the dental hard tis- Fiber-optic transillumination (FOTI) is a widely sues in different ways. This has very impor- faces.

one is able to tell The source of light illumination can be either an whether the site of examination is diseased or not argon + ion laser. In sound enamel. in which electrons of a lower-energy the DIAGNOdent pen (Kavo). as well as some a fluorescent dye (tetrakis N-methylpyridyl por- organic components. Intensity of also detects caries lesions based on fluorescence the near-infrared fluorescence reflects the extent findings (laser-induced autofluorescence of natu- of tooth decay. Systems BV. on the finding that natural tooth structure will absorb the 655 nm wavelength light. proteinic chromophores. The tooth is illumi- value of the test site with that of the comparison nated by a broad beam of blue-green light which site (usually the same location at the contralateral is transported through a liquid-filled light guide. excellent reproducibility were reported. In other ing. the path phyrin. Amsterdam. fluorescence occurs as a result of the conducted to evaluate the devices. targeted prevention for pediatricians. Thus. Mineral that the photons will hit a chromophore. DIAGNOdent pen associated with TMPyP was more capable of identifying this difference in DIAGNOdent DIAGNOdent is developed based mineral loss as well as the gold standard method. Demineralization Correlation was observed between the amount of of dental hard tissue will result in the loss of auto. When they developed for the use in approximal and occlusal fall back to the original level. mineral loss and DIAGNOdent measurements. Xiao A possible consequence of absorption is fluo. filtered images can be captured and stored in a sures on fully erupted first permanent molars in computer. It has using fluorescent dyes. while Quantitative Light-Induced Fluorescence (QLF) decayed tooth structure produces fluorescence in Quantitative light-induced fluorescence (QLF) the near-infrared spectrum [21–23]. thus Demineralized areas appear as dark spots providing helpful information to decide cost. By comparing the numerical ral tooth structure) [24–28]. loss was determined with gold standard method. A new device. but DIAGNOdent in detecting early caries lesions by some can be probably attributable to apatite.100 H. fluorescence is relatively intense. has recently been status are moved to a higher status. This device is matic light at a wavelength of 488 nm. and smooth surface caries. Several in vitro and in vivo studies have been words. After Biberach. good to excellent sensitivity and molecules in the tissue. both caries-active and caries-free children. producing diffuse monochro- and at what severity is the disease. TMPyP) to enhance the performance of lengths are long so that there is a high probability DIAGNOdent and DIAGNOdent pen. energy is emitted in surfaces. The cause of enamel fluorescence is still In recent years. the Netherlands) can be The version called DIAGNOdent (Kavo. peak intensity of 370 nm. Germany) is designed to detect occlusal calculating the loss of fluorescence which . Software (Inspektor Research effective. which has an optical band-pass filter with a the tooth structure or pain to the patient. who had used caused by inorganic complexes. They also found that the detection devices are introduced below. which has the same mode of function- the form of light. a new approach has been pro- unclear. This proposed approach been proposed that fluorescence in dentin is has been tested by Alencar CJ et al. customized to analyze the collected images. or blue very sensitive so that it can be used to analyze the light from a 50 W xenon microdischarge arc initial stage of caries while causing no damage to lamp. Most of the fluorescence is induced by posed to improve the performance of organic components. fluorescence (the natural fluorescence). called fluorescence. tooth in the same dentition). fluorescent- the most caries-susceptible site of pits and fis. In a study by interaction of electromagnetic radiation with Lussi et al. They found that DIAGNOdent and DIAGNOdent The amount of autofluorescence loss can be pen are capable of identifying demineralization measured by devices to quantify the severity of around brackets bonded with resin-modified tooth decay. named rescence. Using a color CCD It has been found to be able to help identify video camera and a frame-grabber. viewed by QLF. Some of these high-tech caries glass ionomer cements.

∆F (average change be measured. ments of QLF could detect differences in remin. mouth rinse. latest inventions and break- throughs in new dental material have tremen- New Caries Detection Methods: Electrical dously reshaped the conception of dental Impedance Based Electrical caries monitor treatment for carious lesions. Temperature variations may also influence the It has been found that longitudinal measure.67 to 0.6 Dental Caries: Disease Burden Versus Its Prevention 101 indicates the severity of a lesion. hand. demineralized the tissue. sodium monofluorophosphate gies are less frequently used in recent times.71 to 0.92. ∆F 0. the lower the resistance becomes. During examination. as toothpaste. more suitable for smooth surface caries examina. These circumstances include examined still under development. or a herbal. is not intended to be utilized but has to be turned Measurements can be performed by closing a to when caries at late stages are discovered. The possibility of adapting it for occlusal positive or false-negative readings may be caries diagnosis as well as secondary caries is recorded. unimaginable without the forthcoming of adhe- tal space and fluid content inside. When a tooth sur- visual demonstration for patients. At circuit of a very weak alternating current through this stage.96. the measuring site methods. tion.80. in %). under some circumstances.91. and both are connected with the device by Therefore. However. according to a study of 91 in vivo samples. face is of interest. specificity ranges from 0. etc. Tooth structures are (ECM) is developed on the basis of analyzing the no longer subjected to unnecessary damages in conductivity of tooth structures. However. And the be limited to a lesion depth of about 400 μm. and daily brushing with sodium fluoride (NaF.3. In a with intra-examiner ∆Q 0. These technolo- 1. its conductivity is than ever before. tooth is much better protected under diseased condition. QLF has a huge advantage in direct should be isolated from saliva. In this way. fluoride placebo dentifrice. At the same time. Natural enamel order to compromise for a more stable restora- is no good conductor for electricity. Intra-class correlation coefficients This equipment is mainly devised to detect (ICCs) for each QLF metric were found to be high caries lesions at approximal sites of teeth. the probe tip can be placed in countless studies have confirmed its accuracy and an electrolyte which covers the surface. excessive dehydration of which evaluated the anticaries efficacy of various the adjacent or other reference sites. However. and (MFP.450 ppm F) dentifrices. which could To now. optical coherence tomography (OCT). further studies are still ongoing. The more sive dental materials. and area number of in vitro and in vivo studies. reported sensitivity for ECM in diagnosing den- It can be used to reliably monitor the caries status tinal carious lesions of permanent premolar and of an individual over time. and occlusal kinds of oral hygiene maintaining products such surface with too complex morphology. by measuring the electric con- ductivity of the test site and comparing it with 6. three measures the patient. Then. when dental caries already come into . near-infrared (NIR) technology. A probe is placed on the site that is to are given: lesion area (mm2). Other high-tech caries detection technologies eralization of early enamel caries on buccal include electrochemical impedance spectroscopy surfaces of anterior teeth following supervised (EIS). In addition. the extent of the carious Tertiary prevention is a last-resort strategy which lesion can be derived [29]. non.98. However. an earth-unit is held in the patient’s in fluorescence. outcome of the measurements in various ways. the 0. it seems to molar teeth ranges from 0.3 Tertiary Prevention findings of the contralateral or adjacent tooth in the same dentition. and ∆Q (area*∆F). 1. the QLF method has been found to be be regarded as acceptable. reproducibility. false- tions.450 ppm F). it has already teeth which have only erupted into the oral cavity been employed in a number of clinical studies for less than 6 months. compared with other caries detection a cord. All those new possibilities are greatly increased because of expanded intercrys.

Many mechanical methods can be employed Toothbrushing movements of different groups of for this purpose. caries can be prevented through repeated rotary movements of the toothbrush perfect oral hygiene. trol is performed by individuals at home. Although numerous clinical studies the level of which is measured by calculating the have revealed no statistically significant . dental plaque con. frequency of daily toothbrushing and its duration cally observed complications are acute or chronic of time but also includes the correct toothbrush- pulpitis. prosthetic dentistry is needed to restore a teeth in a wrong way can also bring about unde- full dentition and maintain proper masticatory sirable consequences. what is to be undesirable complications it will induce if not stressed not only involves stressing the adequate dealt with.102 H. Under This method is so easy to conquer that it can even some circumstances. For enough time. only by performing correct toothbrushing meth- When things become worse. posing potential danger in pulp exposure or even tooth fracture. Therefore. people tion. direction and force. the efficiency of different rhythms of vibration and rotation in all toothbrushing is not always satisfactory.4.1 Dental Plaque Control the gingival sulcus and the interproximal spaces. form effective self-oral hygiene. damage to the ods can they effectively remove the maximum integrity of dentition occurs as a result. Usually. invented to better serve the disabled and the elder. Among those possible and often clini. when directions. removal of dental plaque the majority however. such as multiple wedge- functions. and these the most frequently advocated and most widely movements are often very complex which include exercised [30–32]. essential oil. all that should be done is to prevent the plaque removal rates. Some toothbrushes are specially designed icals. It mainly involves Theoretically. tics. brushing the case. it when mechanical removal is not possible due to In addition. alveolar abscess. Therefore. Chemical removal of dental plaque can be Despite the brushing technique. brush itself is to be carefully selected. between the maxillary and mandibular dentition. ing methods. shaped defects. and many others. Another method to be sug- tiation and progression of carious lesions. However. and each method has its own focus. Xiao being. for different subgroups. Among those. and a number of other seem not to pay enough attention to this fact that less-frequently encountered caries derivatives. a regular-design tooth- with chemicals can only be used as an adjunctive brush with soft round-end bristles is well enough to mechanical methods or used as a substitute for to maintain everyday oral hygiene. Moreover. such as triclosan. In this amount of dental plaque. Now there ferent frequencies. However. the tooth- achieved by administration of mouth rinses at dif. such as children or the sirable consequences as microbes can start to disabled who require a toothbrush to have a tolerate the effects of these chemicals given smaller head and less-likely-to-slip handle. There are a number of toothbrushing methods 6. However very unfortunately. Prevention Horizontal vibrating method (also known as the Bass method) stresses the removal of plaque in 6. electronic toothbrushes are some reasons. periapical inflamma. alveolar osteomyelitis. because it demands dynamic equilibrium of at a reasonable level which does not allow the ini. this method is very much time- Dental plaque control refers to maintaining the consuming and difficult to exercise for most peo- amount of plaque accumulation on tooth surfaces ple. there are unde. kinds of key effective chemical components in Each kind serves a targeted subpopulation of a the mouth rinse solutions. certain age or of particular physical characteris- chlorhexidine. be mastered by children and adolescents to per- ist or dentist as indicated necessary.4 Methods for Caries to choose. benzethonium chem. This often involves different are different kinds of toothbrushes in the market. However. it is performed by a hygien. toothbrushing is bristles have been preprogrammed. gested is reported by Fones.

mannitol. Then it comes lae. and many others). fructose. there are an important caries-preventive strategy. xylitol. eralize enamel crystals if the dental plaque is not wiped away and remain on the tooth surface for a long time. Therefore. Hopefully in the future.2 Restriction on Sugar public to choose. sucrose is found to be One important aspect as well as an important pre- the most dangerous in causing dental decay. Therefore. sugar is very important for the general however. for dental microflora to use or will produce very Electrical dental syringe can produce high. where xylitol-containing prod- Consumption and Use ucts (mainly in forms of chewing gum or soft of Sucrose Substitute drinks) dominate. Such dental floss. in the case of periodontitis or attachment the advocacy of the use of sugar. and odontic wires or partial removable prosthetic stevia sugar and those with low sweetness such as denture. This process. progress once started.3 Reinforce Tooth Resistance Among all kinds of sugar-containing food to Acid (food that contains glucose. despite of its undesirable carioge- Toothpicks can be used to remove food debris. However. nicity. e. addi. and restriction can be applied to either the amount of electrical dental syringe. it is very difficult to com- who have lost the protection from gingival papil.g. substitutes. Dental floss. and tration is much lower than the superficial part. maltulose. 6. these sugar substi- tutes have also entered the market for the general 6. Among the many choices. maltose. number those non-cariogenic species. sorbitol. it might accumulate inside dental microflora and demin. the toothbrush fails to reach some the initiation of dental decay will continue to remote parts of the oral cavity. However. care is needed so that it won’t hurt the health of human as a vital source of energy and adjacent soft tissue. which often takes place in mixed at a mol ratio of 1:1. can effectively help remove dental both. studies on isomaltitol are Oral bacteria. to be able to hydrolyze into glucose. Isomaltitol is a mixture of α-d- acid production and acid toleration. cyclamate. which has been found deep part of dental plaque where oxygen concen. bring us a new choice of sugar substitute. and many others. mannitol and is hard to be metabolized by cario- produces acid. interdental brushes can sugars in nature but have been found to be hard be used to clean those places.6 Dental Caries: Disease Burden Versus Its Prevention 103 differences in the cleaning ability between an of studies.4. maltose. This metabolism end-product will genic bacteria. A lot requisite for tooth resistance to acid is that first of . interdental brushes. Therefore.6-d-sorbitol (GPS) and α-d- sugar contained in food debris to get energy to glucopyranosyl-1. limited amount of acid even if some species have speed projection of water which contains rich managed to metabolize them. plaque on interproximal surfaces. For some subgroup of people nutrition. especially loss therefore leaving the individuals at greater sucrose.. These sugar substitutes are danger of caries attack. restricting the tional accessories can be utilized to perform the consumption of such cariogenic-potent sugars is cleaning.1-d-sorbitol (GPM) which are survive.4. benzoic imine. such as the surface under the orth. the target group in the unbalance of oral microbial micro-ecology are greatly facilitated in maintaining good oral where cariogenic species will tremendously out- hygiene. pletely replace it by other means. This special group foam and can remove food debris for hard-to. especially the species capable of very hot. lactose. Recently. both in vivo and in vitro. Also in recent years. either consumption or the frequency of consumption or waxed or not. of sugars includes those with very high sweetness reach places. Therefore. sorbitol. such as aspartame. toothpicks. have proved ordinary toothbrush that is powered by hand and that consumption of sucrose-rich diet will result one that is powered by electricity. metabolize glucopyranosyl-1.

Systemic application of fluoride refers to addi- mental stage. its various forms have been tested and both the primary and permanent dentitions. before any individual is born. had noticed the reverse relationship between its Many clinical studies have shown very encour- existence in drinking water and reduced rate of aging results with regard to reductions on caries caries. agents such as tablets or drips usually adminis- long (under ideal conditions). Normal anatomy and composition or infrastructure (such as water supply equip- are no guarantee of the lifelong service of the ment). varnish. After birth. tered by professionals. Such vehicles which proper oral hygiene and good general nutrition is have come into being in the western industrial- the only way leading to a healthy full permanent ized countries for many decades include water dentition that will manifest itself years later (usu. Also. Many dif- malnutrition of the mother will influence such ferent kinds of fluoride are used worldwide. the first few years serves as the sodium monofluorophosphate (SMFP). At the same time. when it is found to be existing in the drink. epide- such underlying mechanism. the other side of the story must not countries. the production of lactic acid is greatly and premature delivery as well as low birth reduced. topical fluoride application consumption. in such develop. HA) and form fluorohydroxyapatite (FHA) proper oral health of the mother is of immense or fluorapatite (FA). Alongside than systemic fluoride administration. However.104 H. Further laboratory studies have convinced incidence rates. into the oral cavity gradually and develop various Systemic and topical applications of fluoride physical functions of the oral cavity as well as the have been widely accepted and promoted. Dean ally applied by professionals. methods are easy for personal use at home and From the time of its discovery many years have been widely accepted as important means of ago. maintenance of cavity alongside with saliva. Fluoride is proven miological surveys have shown a steady decrease to be able to reduce enamel solubility in acid in caries prevalence rates worldwide. critical tooth formation process of the child among which most frequently used includes adversely. The rest are usu- ing water which led to mottled enamel. Dr. and salt and ally at the age of 12) and serve the individual life. serves as an equally effective means of fluoride ously. both of which will have substantial Since the discovery of this potent anticaries impact on the tooth formation and maturation for chemical. cation methods that are more feasible and flexible ple personal oral hygiene maintenance. daily oral hygiene maintenance. while the primary dentition that the effective component fluoride ion gets into remains very vulnerable to local contributing fac. (fluoridation of water supply). which are very resistant to significance. milk. indicating . masticatory system. Weapons we have against the war of dental supply. the tite. mouth various forms can provide potent protection to rinses. the permanent dentition is still tion of fluorides into various kinds of vehicles so under formation. These with regular dental check-ups. stannous most pivotal stages for a natural dentition to erupt fluoride (SnF2). between gingivitis and periodontitis of the mother therefore. The first two our teeth. and silicon fluoride (SiF2). fluoride is able to sup- studies have revealed the causal relationship press bacterial metabolism of carbohydrates. cariogenic bacteria and sugar-containing food On the other hand. gel. weight. and foams. the body and continuously secreted into the oral tors to dental decay. crystals (mainly exist in the form of hydroxyapa- Therefore. developing However. fail to have this means of fluoride admin- dentition. Clinical observations and clinical acid. including istration that will benefit the general public. Therefore. Two to three decades later. calcium fluoride (CaF2). This category involves a variety of appli- decay can be a variety of choices other than sim. fluoride in its methods include fluoridated toothpaste. Local contributing factors. Xiao all a tooth must have natural anatomy and proper solutions because it is able to react with tooth amount of inorganic and organic components. which do not have adequate resources be neglected. However. sodium fluoride (NaF). proven to be suitable for clinical use. exist in the oral cavity continu.

6 Dental Caries: Disease Burden Versus Its Prevention 105

the tremendous achievements by widespread use aggregation is small. However, in recent years
of fluoride in caries prevention dentistry has ever there is also some dispute about its safety.
managed to achieve. A great number of clinical studies have veri-
fied that pit and fissure sealing can substantially
reduce caries onset. Systematic reviews on ran-
6.4.4 Pit and Fissure Sealing domized clinical trials have found similar encour-
aging results. In this sense, pit and fissure sealing
Pit and fissure are created in the process of tooth is strongly recommended by FDI, ADA, IADR,
development. They have distinct anatomical fea- WHO, and many other professional organiza-
tures that render them very much vulnerable to tions. And in many countries, it has already been
caries attack. These depressions of occlusal sur- included as part of governmental budget for car-
face (together with the buccal and lingual sur- ies prevention programs.
faces of the molars) always have the bottom part
at deep enamel, enamel-dentinal junction (EDJ),
or even at the dentine. What’s worse, these nar- 6.4.5 Preventive Resin Restoration
row places are hard to reach with routine exami-
nation and cleaning methods. Preventive resin restoration is actually a variation
As a result, it is not surprising that there is of pit and fissure sealing. It involves treatment of
almost always presence of accumulation of mul- susceptible or early carious lesions in pit and fis-
tispecies microbial biofilm, food debris, remains sure (preservative cavity preparation and restora-
of enamelogenic epithelium, organic plug, etc. tion with fluid resin mainly) and combines it with
Therefore, pit and fissure are most often discov- subsequent pit and fissure sealing. This method
ered as the first site of carious lesions of an indi- has adopted concepts of minimal invasive den-
vidual. Data of a clinical study show that about tistry (MID) into caries prevention. However, its
67 % of caries lesions of children at the age of 3 application is restricted to early caries lesions only.
are pit and fissure caries. Another epidemiologi-
cal survey of 25,000 school children revealed that
80 % of all diagnosed carious lesions are located
at pit and fissure.
In the 1960s, on the basis of research findings 1. Baelum V, van Palenstein HW, Hugoson A, Yee R,
on enamel etching and adhesion, pit and fissure Fejerskov O. A global perspective on changes in the
sealant was invented. The underlying strategic burden of caries and periodontitis: implications for
thinking is that if a posterior tooth erupts fully dentistry. J Oral Rehabil. 2007;34(12):872–906; dis-
cussion 940.
into the oral cavity and gets all the vulnerable 2. Widström E, Eaton KA. Oral healthcare systems in
caries-susceptible sites concealed by dental the extended European union. Oral Health Prev Dent.
material the pit and fissure are no longer open to 2004;2(3):155–94.
the oral cavity and therefore will not be influ- 3. Manji F, Sheiham A. CPITN findings and the man-
power implications of periodontal treatment needs for
enced by the microbes that inhabit the mouth and Kenyan children. Community Dent Health. 1986;3(2):
their dangerous acidic metabolic products. And 143–51.
this invention has been proven to be a huge 4. Ainamo J, Barmes D, Beagrie G, Cutress T, Martin J,
success. Sardo-Infirri J. Development of the World Health
Organization (WHO) community periodontal index of
During the following years, the components treatment needs (CPITN). Int Dent J. 1982;32(3):
of pit and fissure sealants have been refined 281–91.
greatly. Now, the most often used sealants are 5. Yee R, Sheiham A. The burden of restorative dental
resin in nature, often belonging to the Bis-GMA treatment for children in Third World countries. Int
Dent J. 2002;52(1):1–9.
system which has many advantages under clini- 6. Brunton PA, Vrihoef T, Wilson NH. Restorative care
cal condition, such as they are easy to use and and economic wealth: a global perspective. Int Dent J.
aggregate, and its volume shrinkage after 2003;53(2):97–9.

106 H. Xiao

7. Petersen PE, Bourgeois D, Ogawa H, Estupinan-Day preliminary evaluation. In: Stookey GK, editor. Early
S, Ndiaye C. The global burden of oral diseases and detection of dental caries II. Indianapolis: School of
risks to oral health. Bull World Health Organ. 2005; Dentistry, Indiana University; 2000.
83(9):661–9. 21. Lussi A, Megert B, Longbottom C, Reich E,
8. Petersen PE. Global policy for improvement of oral Francescut P. Clinical performance of a laser fluores-
health in the 21st century – implications to oral health cence device for detection of occlusal caries lesions.
research of World Health Assembly 2007, World Health Eur J Oral Sci. 2001;109(1):14–9.
Organization. Community Dent Oral Epidemiol. 22. Li SM, Zou J, Wang Z, Wright JT, Zhang Y.
2009;37(1):1–8.doi:10.1111/j.1600-0528.2008.00448.x. Quantitative assessment of enamel hypomineraliza-
Epub 2008 Nov 12. tion by KaVo DIAGNOdent at different sites on first
9. Petersen PE. The World Oral Health Report 2003: permanent molars of children in China. Pediatr Dent.
continuous improvement of oral health in the 21st 2003;25(5):485–90.
century–the approach of the WHO Global Oral Health 23. Alencar CJ, Braga MM, de Oliveira E, Nicolau J,
Programme. Community Dent Oral Epidemiol. Mendes FM. Dye-enhanced laser fluorescence detec-
2003;31 Suppl 1:3–23. tion of caries lesions around brackets. Lasers Med Sci.
10. WHO oral health country/area profile. Geneva: World 2009;24(6):865–70. doi:10.1007/s10103-008-0572-0.
Health Organization. Available at URL: http://www. Epub 2008 Jun 7.
whocollab.od.mah.se/index.html 24. Meller C, Heyduck C, Tranaeus S, Splieth C. A new
11. Qi XQ. Report of the third national epidemiological in vivo method for measuring caries activity using
investigation of oral health in China. Beijing: People’s quantitative light-induced fluorescence. Caries Res.
Health Press; 2008. 2006;40(2):90–6.
12. Kidd EA, Ricketts DN, Pitts NB. Occlusal caries 25. Heinrich-Weltzien R, Kühnisch J, Ifland S, Tranaeus S,
diagnosis: a changing challenge for clinicians and epi- Angmar-Månsson B, Stösser L. Detection of initial car-
demiologists. J Dent. 1993;21(6):323–31. ies lesions on smooth surfaces by quantitative light-
13. Wenzel A, Larsen MJ, Fejerskov O. Detection of induced fluorescence and visual examination: an in vivo
occlusal caries without cavitation by visual inspec- comparison. Eur J Oral Sci. 2005;113(6):494–8.
tion, film radiographs, xeroradiographs, and digitized 26. Stookey GK. Quantitative light fluorescence: a tech-
radiographs. Caries Res. 1991;25(5):365–71. nology for early monitoring of the caries process.
14. Ie YL, Verdonschot EH. Performance of diagnostic sys- Dent Clin North Am. 2005;49(4):753–70, 4. Review.
tems in occlusal caries detection compared. Community 27. Yin W, Feng Y, Hu D, Ellwood RP, Pretty IA.
Dent Oral Epidemiol. 1994;22(3):187–91. Reliability of quantitative laser fluorescence analysis
15. Ekstrand KR, Ricketts DN, Kidd EA. Reproducibility of smooth surface lesions adjacent to the gingival tis-
and accuracy of three methods for assessment of sues. Caries Res. 2007;41(3):186–9.
demineralization depth of the occlusal surface: an 28. Feng Y, Yin W, Hu D, Zhang YP, Ellwood RP, Pretty
in vitro examination. Caries Res. 1997;31(3):224–31. IA. Assessment of autofluorescence to detect the rem-
16. Loesche WJ, Svanberg ML, Pape HR. Intraoral trans- ineralization capabilities of sodium fluoride, mono-
mission of Streptococcus mutans by a dental explorer. fluorophosphate and non-fluoride dentifrices. A
J Dent Res. 1979;58(8):1765–70. single-blind cluster randomized trial. Caries Res.
17. Côrtes DF, Ellwood RP, Ekstrand KR. An in vitro 2007;41(5):358–64.
comparison of a combined FOTI/visual examination 29. Pretty IA, Maupomé G. A closer look at diagnosis in
of occlusal caries with other caries diagnostic methods clinical dental practice: part 5. Emerging technologies
and the effect of stain on their diagnostic perfor- for caries detection and diagnosis. J Can Dent Assoc.
mance. Caries Res. 2003;37(1):8–16. 2004;70(8):540, 540a–540i.
18. Schneiderman A, Elbaum M, Shultz T, Keem S, 30. Muller-Bolla M, Courson F. Toothbrushing methods
Greenebaum M, Driller J. Assessment of dental caries to use in children: a systematic review. Oral Health
with Digital Imaging Fiber-Optic Transillumination Prev Dent. 2013;11(4):341–7. doi: 10.3290/j.ohpd.
(DIFOTI): in vitro study. Caries Res. 1997;31(2):103–10. a30602.
19. Vaarkamp J, Ten Bosch JJ, Verdonschot EH, Tranaeus 31. Gibson JA, Wade AB. Plaque removal by the Bass and
S. Quantitative diagnosis of small approximal caries Roll brushing techniques. J Periodontol. 1977;48(8):
lesions utilizing wavelength-dependent fiber-optic 456–9.
transillumination. J Dent Res. 1997;76(4):875–82. 32. Bergenholtz A, Gustafsson LB, Segerlund N, Hagberg
20. Zero D, Mol A, Sa’ Roriz C, Spoon M, Jacobs A, C, Ostby N. Role of brushing technique and tooth-
Keem S, Elbaum M. Caries detection using digital brush design in plaque removal. Scand J Dent Res.
imaging fibre-optic transillumination (DIFOTITM): a 1984;92(4):344–51.

Clinical Management of Dental
Li Jiyao

Dental caries can be classified clinically as 7.1 The Development of Caries
cavitated and noncavitated lesions according to Treatment Theory
substantial damage to tooth morphology. The
non-operative approach is usually used for non- At the end of nineteenth century, G.V. Black cre-
cavitated lesions or as a preventive measure for ated a dental restoration system according to the
susceptible teeth. For caries with substantial loss susceptible sites and dental anatomical relation-
of dental tissue, an operative measure such as res- ship of dental caries, which involved the clinical
toration is taken. The development of material demands of retention and resistance, in addition
science provides a variety of choices for dental to the property of amalgam, and laid the founda-
caries management. tion for modern restoration dentistry. In the
Dental restoration is an operation on an organ 1950s, Buonocore introduced the acid-etching
with unique biological properties, which involves technique into restorative dentistry. Through the
theoretical knowledge such as mechanics, biol- acid-etching technique, resin composite was able
ogy, materials science, aesthetics, etc. It is possi- to bind with dental hard tissue with a mechanical
ble that the pulp–dentin complex could be lock. The binding mechanism was different from
irritated or damaged in the process of treatment; amalgam. From then on, restorative dentistry
hence it is vital and important to protect the entered the new age of “adhesive dentistry.” After
dentin and pulp throughout the process. the twenty-first century, restorative dentistry
entered the era of microdentistry, by proposing
the concept of early diagnosis, prevention, and
micro treatment; the operative dentistry was
directed toward a biological approach, to prevent
the development of caries and to preserve healthy
dental tissue as far as possible [1].

7.1.1 G.V. Black and Modern
Restorative Dentistry
L. Jiyao
Department of Operative Dentistry and Endodontics, G.V. Black made a huge contribution in forming
West China Hospital of Stomatology,
the concept and principles of modern dental res-
No. 14, 3rd Section, Renmin Road South,
Chengdu 610041, Sichuan Province, China toration. At the end of the nineteenth century,
e-mail: jiyaoliscu@163.com with a rigorous scientific attitude, he carried out

© Springer-Verlag Berlin Heidelberg 2016 107
Z. Xuedong (ed.), Dental Caries: Principles and Management, DOI 10.1007/978-3-662-47450-1_7

V. bonding material developed. standardized restorative system. the undercut. resistance. dental anatomy. which could certainly cause vast damage of dental tis- 7.V. there has been a great leap tions of modern restoration dentistry were laid.1.1. for the first time. was required. standardized pathway and the founda. a ladder-shape Treatment retention form. face. As the resin material and explained the corresponding principle and devel. material mixing. This approach was launched based on the foundation of amalgam properties. this category is still being widely preparation of the cavosurface angle and bevel used. Combining the demands of Buonocore used acid to process the enamel sur- retention and resistance required by restoration. The bonding technique revolutionized tradi- According to the caries location. he cre.2 Adhesive Bonding Technique sue. terms such as mini- the nineteenth century. including total etching and self- the damaged dental tissue base on the principle of etching techniques and the procedure was retention. more careful Clinically. Minimally The development of dental restoration and that of invasive treatment is a branch of preservation dental material are inseparable. the concept of resto- oped a series of basic principles and requirements ration had already been changed. Restoration dentistry then embarked upon a bonding technique. in addition to the design and preparation.3 The Foundation and Principle preparation. modern den- and Dental Restoration tistry suggested a more reasonable theory. According to the properties of amalgam. which was minimally invasive treatment. In terms of cavity tion with the tooth structure. He also proposed certain Traditional dental restoration was based on the demands for each category of cavity. In 1955. in the development of resin composite material The content of restoration dentistry proposed and the acid-etching technique has matured. tional dental restoration. In the twenty-first century. by G.108 L. The system tionize dental practice. principle created by G. Combined with the the- types were added afterward to supplement them. At the end of dentistry. ory of bonding resin composite. and protection of the pulp– simplified as well. Black was to prepare the cavity upon the Bonding systems for dentin have been continu- already weakened dental tissue or after removing ously updated. The descrip. Black in 1908. damaged part. which gener. Jiyao an in-depth investigation into the damage of car. Black's contribution to restoration dentistry. scientific. scientific.V. a cavity with a dovetail. he healthy dental tissue by discarding the sacrifice divided cavities into five categories. contour of the of Minimally Invasive Caries cavity. The clinical application of dentin complex and then restore its original form composite resin has become increasingly wide- and function with a specific material through a spread and the effectiveness of bonding restora- certain process. the preservation of cavity preparation. Black created a mal intervention dentistry. to increase the bonding between composite in addition to the property of amalgam. Two more shaped retention form.V. certain depth of cavity and dove tail. G. resin and the tooth surface and started to revolu- ated a complete restoration system. using ies in susceptible sites and its relationship with mechanical retention. such as the depth. he also proposed a principle based on the demands of auxiliary retention and resistance of cavity 7. it preserved more characteristics of the design and preparation. of more dental tissue was widely accepted as a ing. G. and fill. In the past 20 years. minimally invasive . remov- tion of these systems laid the foundations for the ing a lesion by operation and then restoring the development of modern restoration. ladder- ally covered the basic types of caries. tion has also been proven because of its long-term The knowledge of cavities is a major part of results. and the removal of weakened enamel. and in combina. In the literature.

remin. Martin et al. and angioplasty. but not replacement. demineralization. MI is an abbreviation of minimal inter. self-etching primer adhesive merely a small part of the complete treatment. the process from the demineraliza- Modern Oxford Dictionary. and placed emphasis tooth.e. could strengthen the absorption of calcium and ervation of healthy dental tissue when removing phosphate and form fluorapatite on the tooth sur- caries lesions. and treatment. These techniques dental caries lesions. the greatly enhanced. and restoration material could not match the healthy caries in pits and fissures. laser fluorescence technique. but when in In terms of the biological study of dental tis. which greatly dental tissue in terms of physical. to prevent the development of that the enamel and dentin demineralized. proposed four basic principles for saliva buffering capacity. When the pH of the interface between den- on the treatment switch from dental operation to tal tissue and plaque was below 5. Peters et al. fulfill caries prevention. were particularly used for diagnosing hidden Modern material science proved that dental caries. a demineralization– of how caries develop. the development of ing the different statuses of caries. it showed remineralization. fluorine-containing environments. and constitute a multi-factorial ing to total-etching bonding (1980s). Tyas et al. It minimally invasive dentistry focuses on the pres. mechanical.V. dental tissue. The micromechanical bond. decreased the sacrifice of healthy New techniques of prevention include enamel dental tissue to obtain sufficient retention. etc. In the In the past. and then one-step adhe. Removing healthy dental diagnosis. pit and fissure sealant. demin- principle of G. Black. The dentin initially reversible. cavity were varied. in addition to the traditional operation switches to nonsurgical treatment. tion of the tooth and anticarious ability are cially the process of remineralization. and preventive decreased the chance of microleakage. there was also microme. ity was generally considered irreversible. fiber-optic transillu- minimal invasive dentistry: lesion control. remineraliza- sue. lighted the importance of the interaction tional requirements. instead of the “extend to prevent” face. Fluorapatite is highly acid-resistant. With the development of between doctors and patients when a dental adhesive material. it showed biological method. small caries lesions. including bacterial counts. long-term cooperation sive systems (2000s). total-etching chronic disease. mination technology. the purpose is to retain as . the process of dental tissue gain- dentistry [2]. espe. of light imaging technology. including early diagnosis. pH recovered.7 Clinical Management of Dental Caries 109 dentistry. believed that Fluorine played an important role in this cycle. tissue and restoring the cavities with traditional The new idea about prevention has high- filling material certainly could not meet the func. but not minimally invasive matter of fact. i. and small mally invasive dentistry. and the For now. As a vention dentistry. between doctors and patients must be built to ing mechanism produced solid bonding with achieve that. such as early dental material has laid the foundation for mini. and micro dentistry were used. tal tissue as possible. is widely believed and accepted that caries are chanical bonding in the hybrid layer. and enhanced the sensitivity and accuracy of early biological properties. believed that minimal ing and losing calcium and phosphate ions was intervention dentistry focuses on the knowledge carried out alternately.5. Treatment from the doctor is wet bonding (1990s). eralization starts at pH < 4. and restoration. revolution of diagnosis measurement. electrical impedance tech- eralization of early caries. resin restorations. to systems (1990s–2000). As the dental caries and preserve as much healthy den. dentin collagen and finally the formation of cav- tistry. in addition to the etiology of caries.5. nonvisible trauma. the method of diagnosis for detect- novel view of prevention. infection. remineralization cycle on the surface of the prevention. minimally invasive tion of dental hard tissue to the degradation of dentistry has the same meaning as microden. It chemical dentin bonding. minimal surgical nology. proximal surface caries.. early caries. mainly caused by bacterial bonding system developed from no-etching bond.

To control lesions. a expansion during cavity preparation. irreversible loss of dental tissue. have overcome the excessive treatment. Early diagnosis and personal treatment. Infected layer: this layer of the tooth structure tion. gen- removal. the enamel layer such as plaque and saliva. fluoride ies monitoring. prevent caries Atraumatic restoration. and change the conditions for the development of and improve salivary function. which can easily cause remineralization and filling. ties. in addition to early car. which affects calcium. ion uptake. to implement minimum interven. and only by the use of dental surgical meth- cation. and viscosity to achieve the goal aspects: of caries prevention. The change of bad oral habits. eral oral condition. Explain to dental caries. eating habits. Treatment and effective control. the establishment of personal. Control of cariogenic bacteria. Focused prevention and effective interven. At the early stage of the lesion. and the adjacent teeth also needs to be consid- ered. and to confirm treatment the the laser treatment of dental caries. reduce the amount of sugar intake. Based on the layers from outside to inside: diagnosis to build up prevention treatment programs. and to control complex. the effective use of modern diagnostic techniques niques such as amalgam bonding.110 L. At the same time. using has been completely denatured and bacteria smart materials. Demineralized layer: this layer has a certain preservation of dental health. the use of mouthwash. sandblasting caries activity through the history of dental caries. flow. In tion. or new technologies. Jiyao much of the healthy tooth structure as possible control. prevention. be needed to control bacteria or adjust the pH of ment plan is reflected in the following three the saliva. will concept of a minimally invasive dental treat. effective method of restoration of tooth structure. and other plan by performing observation. an increase in patient communi. to maximize the 2. plaque the past it was thought that the demineralized . loss of the healthy tooth structure caused by tra. 1. thereby reducing the incidence of patients the causes of dental caries. thus preventing als or technologies in cavity restorations. phosphorus. especially in the the presence of pathogens first needs to be con- children with an extreme fear of dental treat. Minimal surgical intervention is the most 1. tooth colored and prevention systems to control bacteria before material. ning system. ing the patient’s poor eating habits and oral Modern caries treatment pays more attention hygiene habits. complications when near pulp. the relationship the demineralization and promote remineral- between the restored tooth and periodontal ization. fold still exists and can be re-mineralized. and the risk of cross-infection. but the collagen scaf- 3. level of demineralization. and prevent secondary caries. ized dental files. and is difficult to remove. diagnosis through treatment plan- be considered. ods. The cavity can be roughly divided into two 2. Plaque accumulates in the cavi- Streptococcus mutans. between occlusion and periodontal health. trolled. Through individual caries risk assessment When caries progress to dentin. making the development of dental caries. assess caries risk. sional dental care and early caries and the proximal contact between the prosthetic treatment. and evaluation of forms cavities. chemical–mechanical caries removal. replace the damaged tissue. Implement the concept of profes- health. For patients at a it possible to get rid of the traditional preventive high risk of caries. the enhancement of patient Remineralization repair is then unlikely to suc- management. etc. Lesion control is a prerequisite for successful ditional dental drilling.[3]. through ment. composite resin inlay. New tech. Minimizing patients’ anxiety and pain Minimally invasive dental operation process: caused by the fear of dental treatment should also patient visits. correct- dental caries. to treat rather than simply settled. ceed. and improvement of patient loyalty. use new materi. guide patients to benefit from to the biological response of the pulp–dentin professional dental methods.

2 Minimally Invasive Cavity twenty-first century has ushered in the era of Preparation the minimally invasive treatment of dental caries. dental car. does not produce vibration and heat.2 Current Management in 1945 with the first air abrasion machinery of Dental Caries and Its available in 1951. carious dental surgery to biological treatment. As dentin is moist. Hence. These techniques Therefore.7 Clinical Management of Dental Caries 111 layer should be removed.and ies focuses on the prevention and management energy-efficient. abrasive particles toward the affected areas in the cavity. toxic particles. all using air abrasion. dentin. . Current dental caries treat. The follow- carious status instead of caries-active status. If it is accompanied by 7. a beam of strong abrasive particles can Technique reveal and blast the stain away in addition to the decay. non- Under the influence of minimally invasive den. The principle of air abrasion is to apply highly pressurized. this layer can be remineralized. more time. tially replace the high-velocity gas turbine cav- the development in the treatment of dental car. and minimally invasive treatment. Air abrasion can par- According to the progressive stages of decay. vation of the tooth structure. dental caries treatment has shifted from accurately remove the enamel. The interior of the ies treatment technology has also developed prepared cavity is smooth. such as aluminum oxide ions.1 Nonmachinery Preparation Air Abrasion Air abrasion was first introduced 7.1 Minimally Invasive Treatment decay. reduces the likelihood of and the systematic evaluation of the effect of microfracturing.2. After visual examina- using the best technology to achieve the best tion. It is well cal treatment at an early stage. It reduces the stress between the filling and minimally invasive treatment of dental caries the tooth structure. ing briefly summarizes the minimally invasive With the promotion of mineralized material to treatment techniques. it should be removed tooth structure as possible. to tistry. It is quieter. but recent studies of the caries treatment techniques should suggest that the demineralized layer is a pre.2. the blackened part of the cav- ment should be an optimized treatment regime. Accordingly. the air abrasion system aims strong treatment outcomes. nonsurgi. and old fillings. ity preparation. ity should be examined. foundation for the application of new technolo. in people suscep- the infected layer. 7. focused pre- vention. it can be removed with ease. Broadly speaking. tissue.2. the modern view is that the removal are mainly used in the early stages where dental of diseased tooth structure should be limited to caries have not yet developed. the The minimally invasive treatment of dental caries particles bind on its surface rendering it unable emphasizes the preservation of as much of the to exert its effect. the 7. hence prolonging the life of the composite resin restoration has provided the fixture. and the surgical received by patients and maximizes the conser- treatment of the cavity. and elastic. occlusal surface. Based on the understanding regarding the early diagnosis of dental caries. technologies are also included. the nonsurgical treatment repair. The air abrasion system has Development evolved greatly since then. and requires no anesthesia as it of people susceptible to dental caries. To aid early the detection of caries on the gies and materials. If the blackened area is a stain. The clinical application of the fill. making it easier to considerably. keeping surgical manually or using a mechanical machine before intervention to a minimum. thick. and in the prevention of car- ies in sensitive areas. emphasize a conservative approach.2. tible to dental caries.

Open wound or recent tooth extraction. However. car. Air Polishing Air polishing delivers high. caries. This solution causes 2. pump. A severe allergy to dust. a heater. Laser cavity preparation is have existing fillings. On the downside. Compared with other caries removal techniques. coronal caries (especially deep coronal . the partial disintegration of the collagen in the 3. The ideal laser should be able to manage both when compared with the high-velocity turbine. Air pol. vibration or anes- hard tissues need to employ other types of lasers. This technique consists of two component mixtures. Carisolv was introduced – Carisolv gel tion. Recent placement of an orthodontic The uptake of this technology was not great as it appliance is expensive. before using tubules. Jiyao The disadvantage of this method is that Chemomechanical Caries Removal because it is easier to remove dentin than enamel. there is no noise. The Carisolv reagent of sodium bicarbonate aerosol. Air pol. Hence. Caridex. and special hand piece. asthma. with: was introduced into dentistry. and does not junction with a dental drill to gain access to the require anesthetics. thus limiting its role in for the following patient group: root/cervical clinical practice. Er:YAG is the most those caries that cannot be directly accessed or selective of all lasers. Subgingival caries of additional equipment. The CMCR procedure can handle most dental aluminum-garnet (Nd:YAG). a hand tool can be used to remove the cementum. and chronic N-chlorinated-DL-2-amino butyric acid obstructive pulmonary disease. nonvibrating. before eliminating infected tissue using machin- Contraindications to air abrasion include patients ery. thetics. other traditional caries removal techniques. One of the was originally designed for stain removal and it is component mixtures is a red gel composed of now also used to remove crown fillings. and requires a lot 5. lysine. Active periodontal disease. Chemomechanical caries removal (CMCR) uses it causes the overhang of enamel. whilst not affecting any healthy dentin. (GL-101E) into the cavities. This method can selec- tion of the caries to remove any remaining tively dissolve carious tissue quickly (around decayed dentin. Clinically used lasers the operating time is longer and requires alterna- that can cut through dental hard tissues include tive methods to gain access to and repair some erbium:yttrium-aluminum-garnet (Er:YAG). providing a new alternative to of the tooth. 4. has no smell. which does not cause a significant amount and Carisolv hand tools. surgeries involving and the tooth. bon dioxide (CO2). the first CMCR system. In ing healthy tooth tissue. caries removal and preparation. Caridex involves the intermittent application of pre-heated 1. Lasers Lasers can be used to perform surgeries CMCR can effectively remove the smear layer of on dental soft tissues as they do not cut through the cavity. producing a cutting effect. neodymium:yttrium. reinforce the bond between the filling dental hard tissues. Recently. which requires chemical agents to soften the dental tissues trimming of the enamel with the drill. CMCR can be used in con- precise. they can also prevent hypersensitivity Carisolv to remove the caries. In 1985. CMCR has been re-introduced to pressure jet of sodium bicarbonate to the surface the dental industry. the machinery The CMCR method should be first considered is bulky and expensive. and patient acceptance is high. leucine. softened carious tissue. and sodium hypochlo- ishing is not very selective when cutting the tooth rite. It is mainly used in the final prepara. cavity. postoperatively. glutamic. As lasers can seal dentinal cavity area or remove the old filling. They all caries. 30s). accelerating the removal of dental caries. undermining caries. and Ar:F. It can be used alone or combined with have selective abrasive properties whilst conserv. system. After applying the mixed Carisolv reagent to structure and can damage healthy dentin and the cavity. including memory cell. A new CMCR ishing differs by using an aqueous friction solu. time-consuming. dental hard and soft tissues.112 L.

the buccal or lingual surface.2. adjacent to filled fissure caries on the occlusal 2. different shape and varying depths of the fissure 3. velocity turbine hand tools to prepare dental cavi- ties. Using this drill together with sal cavity. Then glass ionomer or composite resin is used for restoration. thus. and it is necessary to maintain the treatment. and other cannot be preserved. and promote remineralization.2. pre- Slot Preparation Slot preparation. is an effective method of preventing fissure car- 2. Sealant is mainly made of resin. if the marginal ridge ponents. and conical. The main body of sealant resin pared into a box shape without a dovetail.2. to maintain the integrity of the marginal ridge but the operator’s sight is not blocked by the head of it is not prepared as the classical proximal–occlu. Designing of cavity preparation ent. Pit and fissure sealing is mainly used for suspi- not preserve its integrity or the marginal ridge cious fissure and pit caries as well as deep grooves has been destroyed. proximal caries. help of groove retention. In 7. cavity caries preparation and finishing. metabo- tooth is maintained. oval. mal contact. predilection sites. carious tissue is approached from tion. and prepared especially needle-phobic patients. also known venting bacteria and food debris from entering. Pit and fissure sealants may isolate the fissure and the oral environment. 1. is designed mainly for to achieve the purpose of caries prevention. caries located on the edge of the crown or When the caries is underneath the interproxi- bridge abutment.7 Clinical Management of Dental Caries 113 caries). components. lites. micro drills for microscopic preparation. and mal surface of the teeth. to obtain precise tooth Tunnel Preparation Tunnel preparation refers preparation is called “microscopic dentistry. burs is longer than that of traditional ones. It can be divided into the follow. under the microscope or loupe. the technique of using the principles of minimally invasive dentistry. The marginal ridge of the tooth can be kept intact. material. and pediatric patients. the cavity is only pre. interproximal contact between adjacent teeth. To maximize healthy tooth conservation. as mini box preparation. The occlusal surface of the tooth formed a tooth is avoided during cavity preparation. and a number of auxiliary com- focuses on carious tissue. completion of canal prepara. this method can provide normal The mechanical rotary technique uses high. Normal contact relationship with the adjacent during development. fluoride. bisphenol-A-glycidyl methacrylate . burs Microscopic Preparation Techniques To mini- in proper size are chosen in practice in relation to mize invasive trauma. thereby enhancing the resistance of the Pit and Fissure Sealing Pit and fissure sealing remaining tooth structure.2. this is also called internal preparation. and food residue often accumulate at caries 4. Overhanging of repair materials is prevented. dyes. integrity of its surface. such as fillers.2 Mechanical Rotary Technique most cases. If the tooth surface that is adjacent to tooth-colored bonding materials for repairs can the lesion has demineralized but not actually better reflect the purpose of minimally invasive damaged. Micro drills can be round. Fluoride sealants can continuously release fluo- ing cases: ride. Caries is close to the marginal ridge and can. Advantages of this method are: 7.5 mm apart from the marginal ridge. the hand piece. The shank of the preparation can enter from the occlusal surface.” to the occurrence of caries located on the proxi. those with a into a box or disk shape with the auxiliary dental phobia. and oral bacteria. provide barriers. those in whom anesthetic is contraindicated.3 Minimal Invasive Prevention Technique 1. Injury of the proximal surface of the adjacent ies. a dilu- contact. if the lesion is more than the operator can select different drills for fissure 2. an initiator. Caries is located underneath the interproximal surface.

Because it does not use the lin solution. secondary enamel hypoplasia. traditional extension for prevention. Both of these two formu- with composite resin or glass ionomer. phate solution. and difficulties with be gently removed. Jiyao (Bis-GMA). which extended to the buc. or a fluoride gel are commonly cal lingual ridge. This method removed minimal tooth development of caries. according to the size of the caries. By local applica- extended to 2 mm away from the buccal–occlusal tion. The surface (such as buccal. on which cavi- suitable depth of the fissure is no more than half ties have not yet formed. kill bacteria. The advantage of preventive resin restorations Remineralization Treatment For early enamel is using glass ionomer composite resin as filling caries that have been demineralized and softened. no longer brown. then bonding with sealant by performance. is a commonly used resin with good chemically. and is an effective method for preventing the terminating the development of the caries lesion. it provides etching technology and the resin material filling convergence and an antibacterial effect. The main agents of silver nitrate are 10 % sil- ies and provides a new approach to the treatment ver nitrate solution or ammonia silver nitrate of fissure caries. and the occlusal sur. For the grooves on the cusp prepare cavities preparation. only remove the infected enamel or dentin at the which can combine with proteins to form precipi- lesions. or get rid of superficial structure. with few technical requirements. 8 % stannous fluoride solution. using tates. or a sand stone point bur the site should extensive shallow caries. it can turn into black reduced silver. bacterial growth. Preventive resin restorations solution. but produced lasting anti-caries effects. resin restorations” to treat suspicious fissure car. thus preserving more healthy dental tis. further development of caries. and is considered safe and Simonsen suggested performing “preventive effective. such as 75 % sodium fluoride and evenly parallel to the surface. Drug therapy is mainly applied to early and no worries regarding fallen sealer. When it is applied to zones of sures combined with pits and fissure sealing and caries. in high up the early fissure caries. lingual).e. and the rest to form insoluble acid fluorapatite. enamelo. piece with a pear-shaped diamond. plugging gaps sealant. surface. and binding with enamel mechanically or the appropriate drug treatment to re-deposit . cal and lingual surface. only a and with the addition of 25 % iodine it results in amount of carious tissue is removed and restored off-white silver iodide. It is a preventive mea. inhibit bacterial metabolism. concentrations it has a strong corrosive effect and face coated with sealant. and promote can undergo enameloplasty. Enameloplasty Noncaries fissures were drilled out to form a shallow plate shape. making it easy Caries Pharmacotherapy Caries pharmaco- to clean and keep free from caries. no tooth Preventive Resin Restorations In 1977. thus blocking and sue. The prepared cavity can be used drugs for the treatment. the pit and lations can penetrate into the enamel and dentin fissure caries without caries is protected by the to coagulate proteins.. in enamel and dentin tubules.V .Black principle. Enameloplasty can be used on 2 % sodium fluoride. sodium monofluorophos- fissures that are close to or across the molar buc. Fluoride has no corrosive stimulation to soft tissue. Silver nitrate is a strong corrosive agent. a diamond bur can be used to remove Fluoride. which causes monds. can kill bacteria. superficial caries of the enamel thickness. and also to prevent G. until the groove is glycerol paste. caries. these fluorides can penetrate into the enamel junction or lingual–occlusal junction. Using a high speed hand anterior primary teeth on the proximal surface. with the addition of clove or 10 % forma- fissure caries filling.114 L. When in low concentrations. therapy is the use of drug treatment to stop the plasty. discoloration. but not following the remineralization of enamel. acid and polysaccharide synthesis. chemical bonding reduces the possibility of generating micro-leakage. i. A simple enamel caries in teeth on a easy-to-clean smooth operation. ball dia.

KCl: 1.3.2 g. early caries remineralization of dentin hypersen. there are also hand instruments such as a spoon excavator to cases of silver amalgam allergy. labial. and had no obvious effect on bonding of glass ionomer materials. and simple to operate. then using glass ionomer festations of which are a lichen planus-like cement or other cementitious filling materials for response affecting the local mucosa and the repair. the complex component mainly containing different ratios of calcium.g. and Techniques for Direct There are many types of mineralized fluid. The single component is 7. and fluoride salts.1 The Controversy Over Silver mainly fluorine-containing (e. thereby removing its little cavity preparation and tooth damage as hardness and eliminating caries. and conducts heat and electricity. includ- Currently. and as preven. including the promotion of ment of material preparation and the improve- remineralization of the tooth surface and bone ment in property. In China. The because of the mercury content. Silver amalgam has a history of more than 160 phosphate. it is still widely fication to obtain a class of phosphoserine-rich applied in dental practice. in the mid-1930s. DH2O: good mechanical strength. the silver amalgam in restorative calcification.000 ml). 9 g. it was recorded that silver paste fill- ditions. KF0. but this type of The ART meets the requirements of modern allergy is only limited to the region adjacent to minimally invasive restoration. Amalgam DH2O: 1.e. it started being applied (CPP-ACP). separation. CaCl: has the ideal wear resistance. in American dental practice. nity.. is called remin. a new remineralization agent.1 g. plays great longevity and a low rate of secondary CPP-ACP.3 Current Silver Amalgam are suitable for remineralization therapy. Moreover. structure. However. lingual. the use of a the silver amalgam. etc. with as the body. Casein caries in posterior teeth. KH2PO4: 6 g. dental erosion treatment. the symptoms may be . CPPs can form soluble chelates with the ing has been in use since the Tang Dynasty. and puri. There have been remineralizing agent with CPP-ACP as the main reports that mercury can cause adverse effects. dental material has obtained the approval of als. and it is inexpensive 1. the main mani- remove caries tissue. moreover. has been used clinically. promoting the absorption of miner. In amorphous calcium phosphate (ACP). occurrence of skin erythema. CPP-ACP has a wide range of appli. many international health organizations.2 g. Early enamel caries on the smooth surfaces (buccal. casein 1826 in France silver amalgam was used for tooth phosphopeptide-amorphous calcium phosphate repair. while calcium or years as a dental restorative material. CPP-ACP is used in the treatment of ing the WHO. and people susceptible to caries 7. Restorations [4] which divided into single component and com- plex components.. i. Although silver amal- (casein phosphopeptide.7 Clinical Management of Dental Caries 115 calcium and remineralize. Under neutral or alkaline con. and the best preservation of tooth eralization treatment. palatal or proximal). by hydrolysis.000 ml). inoxidizability..g. silver amalgam also dis- In recent years. there still has been no evidence reporting the direct Atraumatic Restorative Technique Atraumatic causal relationship between silver amalgam use restorative technique (ART) refers to using only and adverse effects. amalgam and its application in tooth repair tion in caries-susceptible patients. Because it fluoride salt is the main ingredient (e. nerve toxicity. bioactive peptides. such as white spots. However until now. CPPs) used casein as a gam is not satisfactory with regard to aesthetics raw material. ingredient shows broad application prospects in such as kidney function damage. possible. there was doubt regarding silver sitivity. and has an effect on cariogenic bacteria. reduced immu- caries prevention. NaF: 0. With the develop- cations in biology.

grooved. expected to increase. 7. The distance of healthy tooth tis- in a molar. and the status of silver amalgam in tooth repair has changed.3. amalgam may also be used as post and core mate- From the perspective of public health. the need to restore the tooth cusps. technique has been put forward in the twenty-first century. restoration. Moreover. However. rial.1 Cavity Shape Preparation ver amalgam in posterior tooth repair at present. or if there is a ture or deform and restorations should not be mercury allergy. The principle of cavity shapes of silver amalgam although some research has been carried out that restorations consists of removing the decayed tis- has shown that the longevity of composite resin is sue. under normal chewing forces bonded fixed technology widely used in dental with proper chewing movements. a box- used to cover it. If there is suction are used to isolate the operation area from large area of crown damage. The depth of gam. tion. sue between two amalgam restorations on the and direct restorations of teeth. and the presence of mercury vapor ing material. rial post and core restoration is superior to the To confine the silver amalgam to the cavity silver amalgam. taken off. unless the preparation is not and silver amalgam restorations should not frac- appropriate for the retention form. Technique ite resin and glass ionomer cement tooth-colored material. with composite resin. 7. removing all greater than for the same sized silver amalgam unsubstantial enamel and sharp ridges.5–2 mm. the mixing of silver amalgam has amalgam in the following situations: early tooth been automated.3. It is noteworthy that with the continuous premolar large occlusal surface or interproximal development of dental restorative materials and caries. the new idea of a minimally invasive ing. the entire crown is and complete the compression backfill. it is not recommended to use silver Nowadays. the bonded amalgam should preferably be used and/or a box-shaped. the cementing mate.3 Silver Amalgam Restoration the physical and chemical properties of compos. shift. sizing the protection of the dental pulp–dentin complex and the functional reconstruction after filling. Afterward. the use of cementing shaped cavity with a restrictive wall and bottom . in the clinic should be closely monitored. After the cavity preparation the rubber dam and sider dentin pins should be considered.3.116 L. outlining the cavity border. tion from silver amalgam pollution should be the repair parts are not comfortable using a bond- strengthened. The silver treatment.2 Indications tissues. and Contraindications The cavity shape for silver amalgam restora- tion requires a high level of resistance and reten- Silver amalgam can be used in almost all poste. the developed countries in Europe The amalgam restorations must have a certain have been gradually reducing the use of amal. It is the basic requirement that tooth tissues rior teeth restoration. However. moisture and saliva. thickness to ensure basic resistance.3. If retention is same tooth should be at least 1 mm. closed off. it still cannot completely replace the sil. adjacent surface cavity of small to medium size. all tooth neck cavity repair. the amalgam-fractured parts repair. with no need for special spots in silver amalgam restoration. and there is minimal decay. protec. empha- restoration [5]. Because of the shortage of 7. premolar and molar occlusal surface or mercury vapor pollution in the oral clinic. It is believed in the following situations that the occlusal cavity of posterior teeth should be at amalgam is preferred: a large complicated cavity least 1. pregnant women. Then.3. Jiyao relieved after the elimination of the silver material is not suggested for repairing cracked amalgam restoration. root canal fill- technology. and then con.3.2 Silver Amalgam Filling circular retention groove retention. without damaging the periodontal 7.

the the forming sheet. out to form an overhang from the gingiva. dimensional adaptation. The subsequent pol- the completion of the operation. the proximal tooth gually to remove excess silver amalgam and fur- cannot play a supportive role. called polishing after carving. It should not appear sparse ate. restoration. amalgam should be performed before removal of After cleaning. disinfecting. for a cavity involving two or layer compaction. and layer upon request. When the cavity shape is more surfaces. but a digging machine and hoe the teeth. sion. it may also effectively prevent the silver direction. General occlusal adjust- pression causing the unnecessary mercury to ment can be divided into two steps. When filling is completed. For a class I cavity on only one tooth of the side of the cavity shape. The forming the ideal tooth shape and bulge. it is conducive to the to provide full compression. of the crest of the adjacent tooth. Using the body to the restoration. thus strengthen. attention should also be paid to both amalgam from overflowing and periodontal the horizontal and the lateral direction to ensure overhang. should also be removed. or feather-edged on the border of the restoration while if it is too big it will affect the adjacent with the tooth tissue. of layer upon layer com. When backfilling. the use of a forming piece is extremely con. ishing. generally using ing. This is advisable before the cavity can be filled. the crest of the adjacent and occlusal cavity. deep pit and fissure.7 Clinical Management of Dental Caries 117 is needed. Next. the restoration should be mon piece of auxiliary equipment used in carved according to the anatomical form and the forming of the proximal surface. to improve the corrosion resistance of . but attention should be paid rence of secondary caries. in addition to considering the vertical neously. When applying compressive backfill of silver amalgam. and drying. silver amalgam is fully solidified. However. and a silver amalgam plug. it is more advantageous to second day after the filling. On one hand. tion evenly. and of the dotted angle to the line angle forming an outreach gap. Before silver amalgam fill. other meth. is to ensure ing the intensity of the restoration and the that the surface of the silver amalgam restoration mechanical properties. and the early contact point of middle occlu- tooth body closely. but not a shape and size of the wedge should be appropri. Because the matrix band with the teeth can also be used. A special carving instru- wedge may be inserted between the necks of ment is available. the matrix bond is used to develop the erally believed that a thickness of 1 mm is able artificial wall. in the case of the silver amalgam pressed be done in accordance with the anatomical shape. and then to pression. namely squeeze out and causing the air which mixes immediately after the filling is completed and the with it to discharge. which stimulates the periodontal that the silver amalgam restoration has a three- tissue. a short push and pull. Before ciple of layer upon layer compression. When the adjacent relations. It is gen- the filling. using an ovoid hoe light venient if it has proximal tooth support. polishing should age. The wedge is a com. In trimming the edge of silver amalgam autostirrer completes the attri. the occlusion should be followed. pressure. thus. which should be from the tooth varnish is made from resin materials. simulta. the sharp edge can be used. When com. The backfill process makes should be checked and adjusted to prevent a high silver amalgam go into the cavity and fit with the bite. Usually. be carried out promptly. Silver amalgam carving should closed. coating and painting can reduce the occur. an instrument with a matrix band cannot fit the tooth neck well. it is essential to use a matrix bond large. the surgical prin- surface. and stretching occlusion ger is used to carry out the process. more attention should be paid to the prin- surrounding to turn it into a box shape. If it is too small it is not easy to set tight. the principle of attention should be paid to the height of the edge little by little filling. lateral occlusion. For a class II cavity of proximal tooth dam. but for modulator to act in mesiodistally and buccolin- severe tooth body damage. the commonly used to the direction. ther compact the edge of the silver amalgam ods are needed to assist. In class II cavity filling is smooth. The sculpting of the silver shape of the restoration. the structure itself has satisfied this ciple is lateral compression. Then.

They are suitable for class III. tal morphology shaping. such materials possess good mechanical systems [6]. IV. which was produced in the late 1970s Technique has great color and polishability.4. Anterior repairing all kinds of cavities. For macrofill resin composite. and universal. they have been considered to be the best tooth type. dental mor- In 1955.01 to 0. thus. and discolored teeth while posterior tooth type enhances the mechani.04 to 4 μm The properties of resin composites have been and the filler volume fraction is 56–66 %. microhybrid resin and Bonding Mechanisms composite. a filler material. restorations.1 Resin Composites arrangement. As early based on processing for smear layer by etching products. The nanocompos- ite was first reported in 2002. and nano- composite. They are mainly com. the filler used in clinical practice and universally volume fraction is 70–77 %. according to the posi. ing. 7. posterior Thus.4. has better abrasion resistance and transparency. improved surface polish- There are many kinds of resin composites. resin veneers. the filler particle size ranges from 0. resin veneers. For hybrid resin and the tooth surface. According to the inorganic filler particle size. the Modern etching systems can be divided into the filler particle size ranges from 10 to 100 μm and total-etch systems and the self-etch systems the filler volume fraction is 70–80 %. tiny tooth reshap- used in dentistry as a restorative material devel.4 Resin Composites and Direct the filler volume fraction is 35–50 %. they are suitable for Resin composites are types of polymers that are class III. oped based on acrylate. and a photo initiator.118 L. The filler particle size ranges from 0. greatly improved since Bowen invented them in Because small particles fill the voids between the 1962. face with acid to promote the bonding between and also posterior teeth restorations. In particular. and V restorations. and to prolong properties. the filler particle size is 1–3 μm. hybrid resin composite. resin composites can be divided into macrofill resin composite. Jiyao the silver amalgam restoration. Buonocore first treated the tooth sur. den- resin composites emphasize color and polishing. and V restorations. but poorer surface polishing charac- the life of the restoration. so that they are less frequently used at present. which ability. This technique was then ite). the development of bonding large particles. which improved the resin composite (namely universal resin compos- stability of restorations. Microhybrid resin composite refers to the com- posed of Bis-GMA monomers or some Bis-GMA pound filler of large particles and small particles. IV and V restorations. This kind Bonding Restoration of material. their sur- 1974. The total-etch system is also called . can be divided into anterior tooth type. analog. which are suitable for tions in which they are used in the clinic.2 Etching Adhesive Systems microfill resin composite. II. However. ing more widely used and becoming the ideal however. and partial discolored tooth restoration. For the microfill resin composite. This composite has excellent mechanical properties. and they are suitable acknowledged at the annual meeting of the for class I. and dentin res- International Society of etching techniques in toration for classes III and IV.1 μm and 7. cal strength and abrasion resistance. available. teristics. but poor mechanical properties. phology shaping. the microhybrid resin composite technology has led to resin composites becom. and the filler parti- cle size ranges from 25 to 75 nm with a precise 7. discolored teeth restorations. they are not as good as ultra-microfill tooth-colored restorative materials at currently resin composites. which brought about great changes in face polishing performance is inferior to that of dental practice. microfill and nanocomposite. universal composites. and decreased polymerization shrinkage.

e. phate ester or carboxylic acid ester.4. layer and the residual smear layer. the composition is substantially the same.4. which is filled with water between the dentin collagen (this gap was originally occupied by the 7.5). Water is a under the smear layer of the dentin. the demineralized dentin through the gap. The adhe. The example. the combination of etching and pre. hydroxyapatite under the smear layer of the dentin. at the same treatment. The clas. 7. self-etching an organic solvent. then.5 Enamel Bonding hydroxyapatite) to form a “hybrid layer”. to form a “hybrid zone” with hydroxyapatite so sification of dentin adhesive systems is shown in that the “hybrid zone” is composed of the hybrid Fig. 7. and its pH is phate acid) and demineralizes hydroxyapatite above that of the phosphoric acid gel. and surface. sized by dissolving the resin monomer to form According to its acidic strength. For both the etch and the primer in the two- step system and the self-etch adhesive in the one- 7.4 Self-Etch Systems removing it because of the lack of the separate etching step.. the resin monomers penetrate into strong (pH < 1. and water. material Multiple-bottles system: Two-step system: etch+primer+adhesive etch/primer+adhesive Total.1. i. residual hydroxyapatite. The hybrid layer is between the adhesive and dentin Etching is a key step in enamel bonding. are large quantities of hydroxyapatite in enamel. medium (1. resin monomer.7 Clinical Management of Dental Caries 119 “etch and rinse adhesive” because there is a sep. There and is composed of collagen.1 Classification of etch/primer/adhesive +adhesive dentin adhesive systems . Etching Self- etch systems etch systems systems One-bottle system: etch One-bottle system: Fig. key component of self-etch systems because it is sive of the one bottle etching system is synthe. time. for and dentin without the separate etching step. a mixture of water and the acidic The total-etch system completely removes the monomer.5).0). mixture combined with etch and primer pene- treatment. After etching and rinsing. A self-etch system combines the etching and pre- The development of dentine adhesives has treatment as one step when processing enamel changed a lot to simplify the procedure. The self-etch system only makes the smear layer permeable without completely 7. adhesive can be divided into three categories: the adhesive was applied to the treated tooth mild (pH > 1. The acid monomer is typically phos- smear layer using an acidic gel (usually phos.3 Total-Etch Systems step system.0 < pH < 1. However. the various simplified trates into and dissolves a part of the smear layer methods are all from the two systems. the dental plaque. buffering the shrinkage stress produced by arate etching step that completely removes the the polymerization of the resin composites as an smear layer by an acidic gel and demineralizes “elastic buffer”. The hybrid in which the surface layer turns into water-soluble layer helps to reduce postoperative sensitivity monocalcium phosphate during phosphoric acid and form a better marginal seal.4. Meanwhile. involved in the ionization of acidic components.

which forms the resin tags that can gener. Therefore. The bonding strength is tially removed. the weak ized. dentin is sophisticated. the demin. Jiyao alba. Consequently. called resin tags) are formed on the enamel side it is difficult to perform the treatment of dentin. and the low-viscosity adhesive penetrates acid can partially remove the smear layer and into the micropores of the enamel via the capil. but surface layer. However.5–15 μm. lead to the appropriate opening of the dentinal laries. a polarized surface is formed. Owing to the orientation of it is insufficient for untreated enamel and scle- hydroxyl and amino on the tooth surface after rotic cementum. the bonding is beneficial for wetting and penetrating of the strength is very low and there is no enamel pre- adhesive. After demineralization of the . the rough enamel surface is improved so that the adhesive more easily penetrating the micro- structure of the tooth surface. the smear layer mechanical interlocking is obtained by etching can be thoroughly removed. water. clinically acceptable for dentin and etched face are removed. When the adhesive is cured. thereby exposing a clean fresh enamel treated using the self-etch method. It is widely believed that the bonding strength of self-etch systems: the prime mechanism of dentin bonding is the formation of a hybrid layer or hybrid zone. the bonding inter. ment of dentin includes three aspects: removal of eralized enamel layer is thinner than that treated the smear layer. The increased surface energy of enamel For the one-step self-etch system. In addition. Removing the rodless enamel to obtain a The treatment of dentin is described as rough enamel surface. It is generally accepted that 30–50 % of etching. total-etch systems are In spite of the self-etch system gaining in pop- considered a better adhesive system for enamel ularity. 0. thus strengthening 7. In the total-etch system. The dentin contains a lot locking force. prisms and interprismatic areas are demineral. There are two methods of improving strength of the adhesive.6 Dentin Bonding the interaction of adhesive and fresh enamel. the two-step self-etch system is used. and its thickness is materials and enamel. The degree of treatment of the smear Etching technology is the general method for layer directly influences the bonding effect of performing enamel bonding. and liquid effused from the demineralized interprismatic area of the enamel.120 L. there is a smear layer caused and countless micro-protuberances (usually by instrumental cutting of the dentin. Then. dentinal tubule large quantity of cured adhesive filled in the connected with pulp. thus bringing about the benefit for dentin occurs. the dentin surface is treated 2. the polymerization of the adhesive tubules. These mechanical The smear layer is caused by the formation of anchored structures formed by resin tags and metamorphic organics and inorganics during the enamel provide the prime bonding force for the bonding surface preparation. the wettability of material. The etched enamel will increase the postoperative sensitivity. It can be observed by SEM that a of organic components. the bonding strength is accept- phosphoric acid enables even demineralization of able when the enamel is beveled and prepared. improving the surface activity of by phosphoric acid gel because of the higher pH dentin. whether the one-step or ate the micromechanical interlocking system. which main adhesive mechanism. of the bonding interface. phosphoric acid treatment. the treat- For the two-step self-etch system. In the case of the self-etch system. 1. tubules. promoting the penetration and bonding of adhesive. thus. The surface property and interior structure of the face generates a considerable mechanical inter. Using phosphate acid to pre-etch the enamel by the etch so that the smear layer can be par- before self-etching. At first. In this method. and food residues attached to the tooth sur.4. dentin. and the formation of resin tags is the excessive opening of the dentinal tubule. follows. phosphoric acid etching of the enamel is bonding. bonding. still the gold standard for testing new bonding After the etching process. but probably leads to treatment. the enamel surface.

a severe attrition and will obtain a solid bond with the dentin because cusp defect need to be excluded. Almost all the den. remaining tooth structure. the adhesive is cavity. Design cesses mentioned above are simplified into a one-step or two-step procedure. etrate into the micropores of collagen fibers and The following situations should be taken into dentinal tubules to facilitate the subsequent pen. and this need to be considered in bonding restoration.2 Requirements for Restoration ment of the dentin bonding system.5. which act on the bonding inter. in addi- belt and the opening of dentinal tubules.5. the microporous stent of which can also be used for an abnormal shape or collagenous fiber is exposed to form a porous the color of teeth in cosmetic restoration. while increasing the resistance of the is a significant issue. whether the treatment especially for the one-step self-etch system. dental tissue. resin composite has been widely used lesion. thus. the inadequate penetration of the remaining hard tissue also need to be consid- resin into the tooth structure may also accelerate ered. teeth. ing strength is acceptable. and retention of the restoration relies on indirect restorative dentistry. tion to the restoration of endodontic treatment the primer is used. Acid etching followed by bonding provides The durability of the self-etch bonding system retention. As time goes on. then. except for a crossbite and clenching. account: in the anterior restoration of a class IV etration of the adhesive. is for the placement of the original prosthesis. which posterior teeth restoration. the coated. The tooth types. owing to the hydrophilicity of the acidic mono. can cured in situ. and the Shrinkage stress caused by the polymerization of reserve area extends to the range of the sound resin composites. combined with Restoration Technique the characteristics of bonding restoration.7 Clinical Management of Dental Caries 121 intertubular dentin. and the relationship mer in addition to the high water content to main. between the edges of the tooth preparation tain ionization of the acidic monomer. size and type of defect.1 Indications tooth structure as possible in the premise of and Contraindications removal of infected tissue and caries staining. 7. What is more. It can become wet and pen. the bond. Cavity shape is determined by the area of the Currently. Meanwhile. the etching. Along with the develop. and blood. The principles of cavity preparation for resin composite restoration are based on the principles 7.5. We do also not this zone contains many resin micro-protrusions use resin composite if the cavity cannot be com- and large resin protrusions of the dentinal pletely isolated from saliva. needed. may ultimately even affect the bonding to enamel. the bonding strength is continuously decreased. results in reduced dentin bond strength if the dentin bond strength cannot resist it. The principles emphasize preserving as much of the 7. the the position of the teeth in the dental arch. . at last. the pro. the residual unsaturated fluid. face. the resin composites can be bonded to dentin. After the primer and the adhesive are teeth deficit. 7. For hybrid zone) with dentin collagen fibers. gingival crevicular tubules. they form the hybrid layer (or be considered a direct composite restoration. the mechanical force of remaining tooth the degradation of the bonding interface. which does not exceed one half. the occlusal function. The extension for prevention is not tal defects can be repaired via a resin composite. structure is exposed to the defect. the quantity and quality of the Meanwhile. ethylene of the adhesive copolymerizes with the resin monomer. At the early stage.5 Resin Composite Bonding of amalgam cavity preparation.3 Cavity Preparation ing in secondary caries and dentin sensitivity. This will bring about the formation of gaps or edges result.

the preparation of structure and weak enamel should be removed. should preparation should embody the preservation not be beveled. and the enamel pulp. the retention groove is not ness. or the distance avoided. or stained. the cavity the root surface. where there is no enamel.0 mm bevel edge can be prepared. occlusal surface and an axial wall in the proxi- mal surface. Class V For small to medium-sized class V cav- tin. groove should be made in the axiogingival line rial is not as good as that for the silver amalgam. Class III Cavity preparation should be started ous parts and developmental defects. buccal and lingual exceeds 2/3 of the crown length. possible. especially the enamel thick. On the occlusal surface. and when there is no enamel on the gin- should be removed without extension to the root gival wall. and the bevel rations. especially the functional occlusal tip the enamel wall. trying to save the lip caries. possible. the axiogingival line angle. which is not conducive to bonding resto. For enamel car- and side walls. the retention depends mainly on the retention points in the occlusal cusp the edge bevel is not wall and resin bonding. For a large area of caries. or the edge of the facial surface has been increasing the supporting retention. the bevel edge needed. however. without going deep into the dentin. adding the auxiliary retention ditch at the bottom or as an aid to the retention form. at these parts of the restoration. make a beveled edge.122 L. Withstanding a greater bite force principle. Jiyao Class I The cavity shape only involves the cari. the preparation can be entered directly large shallow dish caries. without extending around the cavity needs to be prepared. and cavities. wall slope. to remove a damaged. espe. with no special shape. only a short bevel of at least 1. Generally. There are pulp walls at the attain a better aesthetic effect. angle. between the incisal and gingival surface For the proximal cavity. the slide ditch should be prepared at side. should be designed as conservatively as then prepare the bevel at the edge of the cavity. and the cavity edge and line angle at the tongue surface. thus. in the same way as the ing of the material along the plane can also silver amalgam. with intact walls should be introverted. Therefore. while the bevel is at sidered. For the occlu- sal cavity. the bevel at the non-occlusal contact at the and all the enamel edges beveled. In cases occlusal surface remains controversial. For enamel from the lingual surface. carious tissue needed. and the spread- axiolingual line angles. without making a special cavity shape. preparation should be as conservative as cavity. The gingival wall. the beveled edge could increase the Class IV The beveled edges and the size of cavity width. to facilitate closing together. Therefore. and in with defects exceed mesiodistally half the contact with occlusal cusp. the dental defects in class IV cavities should thesis is greater than for the conventional cavity. to the self-cleaning area. if the labial enamel has been the enamel. Retention grooves . and the undercut should be prepared in the Therefore. the tongue edge does not should be more obtuse than with silver amal. and a large part is involved in den. the retention Class II The abrasion of composite resin mate. be considered for resin composite restoration. An additional retention Increasing the width of the bevel could groove could be prepared at the axiofacial and enhance enamel bond strength. For the tooth in which defect is limited to one cially the edges. the cavity should be from the facial surface. the occlusal factors should be con. flakes often form and breakage side and the incisal part is intact. less enamel is available in the proximal ities. the carious is easy by force. for the gingival wall parts. stretching to occlusion. to preserve as much tooth edge only needs to be prepared for the enamel tissue as possible. axiofaciopulpal point angle. should be prepared. without proceeding to the dentin. gam. the bevel should be width of the incisal part. Therefore. which means the wear of the pros. at the occlusal contact ies. the depth of the cavity should be limited to surface integrity. Small to medium-sized extended at the buccal and tongue groove. However.

the main problems that affects the longevity of direct occlusal surface and the adjacent surface from composite resin restoration. For a long Composite Restoration time. to improve the organizational flexibility. cavity shape. ite resin is mostly formed of dimethacrylate mol- able edge. mesial and the distal requirements. sensitivity. of Postprocessing Decoration After the restoration. the volu- success of grinding and polishing of the resin metric contraction resin showed that the volume composite is determined by the repair materials changes the effect on the tooth structure and and devices. the routinely. occlusal function. while the character of the polishing is better. and polishing are needed. orientation.1 Polymerization Shrinkage at the adjacent surface.4 The Importance the life of the restoration is extended. The dental compos- coarse to fine.5. marginal polymerizing dental composites. shrinkage stress may result in adhesive failure. For the best Class V cavities. rounding teeth.5. contour. postoperative apparatus and polishing paste. . and evant component and filling characteristics of the other adverse consequences. and better aesthetics. Therefore. shape. in which the area is large and bonding aesthetic. The volumetric con- resin. because it affects the standing of resin composite polymerization color-matching of the restoration. trimming the shape care. similar to the box-like cavity in silver restoration should have a perfect contour and amalgam restorations. but also by the rel. this part was not given serious clinical attention. need to be prepared to prevent plaque accumulation and dyeing. The resulting the physical and mechanical properties improved. tions may cause shrinkage stress at the resin mulation. which is caused by the difference in the stress is not only dependent on the characteristics wear rate of these two components. ecules. The surface quality of the resin is bonding interface stress. postoperative hypersensitiv- hardness of the inorganic filler and the matrix is ity.7 Clinical Management of Dental Caries 123 not only increase retention. contouring. while the bevel edge should be ical shape of the prosthesis adapt to occlusal shaped on the occlusal. The surface gloss structure. The Owing to the restrictions of the cavity. Shrinkage different.5. and match the color of the sur- edges of the wall. The tooth deformation. can form a smooth surface. and the composite/tooth structure interface and/or within aggregation of the resin have been enhanced. a suit. microleakage. and resto- of restoration materials should be similar to that ration techniques. secondary caries. and improvement of polymerization shrinkage and micro-leakage in the smoothness of the surface. secondary caries or microleakage. The integrity and the adaptability of the edge is also improved. attention to the concept of aesthetics. and a good occlusal relationship. and 7. and polishing the smooth surface. A new composition with small particles traction in the bonded resin composite restora- and micro-mixed resin has changed the filler for. causing tooth deforma- not only impacted by the quality of the polishing tion and resulting in bond failure. but can also reduce integrity. a polymer network and volumetric contraction.5 Problems of Direct Resin grinding. At present. whose polymerization reaction produces which can achieve minimal plaque adhesion. the correct under- of the dental interface. the resto- ration is durable and aesthetically pleasing. and this of the composite resin. easy bacteria removal. by removing the flash side 7. Polymerization shrinkage stress is one of the fully. but also on the tooth results in a surface roughness.5. characteristics. blending. should be prepared at the angle of the gingival The appropriate dressing also makes the anatom- and occlusal axis. significantly offers numerous clinical advantages high-quality restoration not only requires decora. the surface should be smooth involves the root surface. but also pays the bite force of the resin. Very simply. Therefore. The retention groove form. and the tooth or the resin composite. 7. The size. in reducing the shrinkage stress generated in tion for the anatomical shape.

layering techniques include horizontal occluso- ticles larger than 400 nm. With a constant amount of shrinkage. the higher the polym- the volume contraction within the resin.1 vol% [7]. can decrease the shrinkage further. and produces more used in clinics. Compared with authors. the use of incremental layering nanocomposite resin particles have a high filler techniques for the purpose of reducing polymer- load and extensive filler distribution. intensity is low at the beginning. wedge-shaped oblique layer- contain filler particles between 20 and 100 nm. the erization stress. a new "soft" curing technique has been reported. Therefore. and greater increment. A relative low-intensity curing light was used C-factor The configuration factor is the ratio of during the first few seconds of the light curing the bonded to unbonded surface of the restora. Incremental layer- main strategy in reducing polymerization shrink. the monomer of composite resin is converted to ing process. the resin is lim. the sists of organic matrix and inorganic fillers. concave deformation at the surface polymer. Jiyao Material related factors Resin composite con. but the polymerization shrinkage stress is ences of opinion about the flowable resin com. Compared with resin compared with the bulk technique. resulting in greater marginal volumetric contraction of the organic matrix.6 % ~ 7. The use of a high-intensity flowable resin composite can be placed between curing light can increase the polymerization the tooth surface and the nonflowable composite rate and mechanical properties of composite as a stress buffer layer. In addition ited in direction and becomes less flowable at the to the curing methods. the bond strength with polymerization shrinkage is mainly caused by the dentin declines. which makes and at the early stage of polymerization. techniques had no significant difference on the ite resin contains less inorganic filler. However. therefore. As the C-factor decreases. the resin the surface polymer sufficiently cross-linked. lower shrinkage. the more polymer- of a flowable resin composite can compensate for ized monomers there are. which shrinkage stress of composite resin. (10 s). shrinkage stress at the interface. increases incremental layering techniques are still widely the polymerization shrinkage. the light tion shrinkage is limited to only one direction. The shrinkage stress increases. the space occupied by inorganic fillers is nized as a major factor in the reduction of not involved in the shrinkage. and then a high-intensity light is applied tion. and the successive cusp build-up technique. the shrinkage stress of each posites with a high filler load have some good increment can be compensated for by the next physical properties. increasing the filler load. high. In recent years. ing resin to inhibit potential stress. Compared with hybrid and microfilled resins. As the C-factor increases. for the final curing. which resin. flowable compos. who argued that different restoration conventional composite resin. the polymeriza. Incremental Conventional composite resins have filler par. Because of the reduction of C-factor. mental layering. In this Incremental techniques are always recog- process. the contact surface between the resin and the the resulting shrinkage stress grows with the cavity walls is minimized and the resin is rela- increase in the elastic modulus of the composite tively flowable during polymerization. the C-factor and shrinkage stress. flows freely to prevent polymerization shrinkage but prolongs the polymerization of the underly- stress. early stage of polymerization.124 L. ing. resin. For incre- composites with a low filler load. there are differ. Currently. hardness. the curing units also . reduces the mechanical performance. with an average of 2. For this technique. microleakage. owing The polymerization rate is the rate at which to the reduction of inorganic filler during the cur. thus. the resin com. Slowing down the curing process can posite used as a base material to reduce release stress during polymerization. Therefore. polymerization shrinkage. but nanocomposites gingival layering. ing is considered to be the conventional tech- age in methacrylate-based composites focused on nique for reducing polymerization shrinkage. The higher the rate. Nevertheless. resulting in ization shrinkage has been questioned by some low polymerization shrinkage.

Total-etch adhesive is recommended for bonding with the 7.5. Above are the foundations for the a subgingival cavity restored without gingival individualized treatment of dental caries. of short duration. and incor. If the position and of Dental Caries angle of the cavity walls. Direct resin restoration as possible from the treatment. reveal that modern dental treatment. there are caused by improper selection of indications. or the aesthetic prop. ing individual systemic health. Any care. The incidence of such sensi- composite and adhesive according to the operat. neglect of the product manual. selection of the appropriate resin sional adjustment. or both. These concepts restorations.5. low-intensity light can effectively reduce the shrinkage stress. of the Treatment of Dental tics of the posterior teeth. retraction. the adhesive the ecological plaque hypothesis. or lessness in procedure and difference in technical insufficient marginal seal if the adhesive is too proficiency may lead to the failure of thick. Debris. of Treatment tine surface. the sensitivity may be due to opened direct composite resin restorations. It requires consid- eration of the tooth position. material. when inadequate understanding of material and mech. Factors includ- surface must be thoroughly cleaned. the best func- will definitely fail if inappropriate cases are tional reconstruction. ing instructions is essential. First. that is initiated by Technique sensitivity. 7. when the cavity manufacturer’s instructions.5. ence on the etching and binding effect on the gen unit.6. location. filler types of resin to meet 7. such as cusp defect. Cavity preparation is another impor- tant factor.6. Caries erties of the anterior teeth. tivity is high and it is difficult to solve.7 Clinical Management of Dental Caries 125 have different effects on polymerization shrink.6 The Prospect the requirements of the mechanical characteris. are not properly prepared. social economic . pigment or carious tissue have an influ- age stress. plaque.5. Although cavity preparation of direct resin restoration does not need strict retention 7.2 The Importance and resistance form. cosmetic tion of successful direct composite resin dentistry. dentinal tubules caused by the etching process. includes the failures after resin restoration or later. In addition. immediately dent on the practitioner. requires as little trauma is also very important. or formance. or shrinkage stress-induced microleakage. Typically. or exposed dentin surface due to excessive occlu- First of all. severe attrition. and volume of the cavity. the cavity is deep and there is not enough base anism. there are certain principles of Individualized Treatment that need to be followed. and the best aesthetic per- selected. Technique sensitiv. a light emitting diode unit using healthy tooth tissue. Strictly following the product Scholars describe dental treatment in the twenty- manual and operating instructions is the founda.3 Postoperative Sensitivity Postoperative sensitivity is described as a moder- 7. first century as micro-invasive dentistry.1 Individualized Ideas enamel surface. which is totally depen. two types of postoperative sensitivity. and adhesive dentistry. is shallow but reaches the enamel–dentin junc- ity is an important factor that affects the result of tion (EDJ). Compared with the traditional halo. Second. hot and cold stimulus. the cavity need re-filling with sufficient rect operation by not following the base material and resin.2 Technique Sensitivity ate pain. adhesive Dental caries is a multi-factorial disease based on failure will result. especially The selection of the appropriate indications treatment of dental caries. mastication. and for bonding with the den. and the bevel of the cavity edge. use of a self-etching adhesive is recommended. restoration.

Individualized treatment plans for that specific treatment and precautionary dental caries against specific risk factors are pro. the risk evaluation can help caries-related microbes are closely related to us to define risk factors for an individual so dental caries. Recent epi. tion method. Some individuals evaluation of dental caries is the major tool have caries because of a preference for sweets for predicting the success rate during han- and a tendency to ignore oral health. To control dental caries effectively. otherwise. colony prevention. the goal of early detection. including caries under the circumstances of fairly constant early diagnosis. ing on populations at a high risk of caries. the buffer capacity of 2.4 The Development the Premise of Individualized of Technology and Material Treatment of Dental Caries Provides a Guarantee for the Individualized The evaluation of the risk of dental caries is an Treatment of Dental Caries assessment of the degree of risk of developing new caries or continuing the progress of existing The development of technologies. 7. high. early prevention. the implementation of oral health care. a the general population can lower the overall quantitative technology of the early diagnosis prevalence of dental caries. To make suitable precautionary treatment plan saliva. treatment. pro- vidual at the time. the success rate is relatively taken against different risk factors for dental car. and a preventive technology with Filtering people at a high risk of dental caries low side effects. a micro-invasive treatment technol- precautions cannot be noticeably increased.126 L. and combining multiple prophylaxes before the provide a guarantee for the realization of the occurrence of dental caries can greatly enhance real sense of individualized treatment of the efficacy of the prevention of dental caries. The functions of the risk vide the premise and guarantee for the individ- evaluation of dental caries are listed as follows: ualized treatment of dental caries. focus- high caries activity suffer from most of the den. Remineralization elderly people gingival recession and root expo. As dental caries is a multi- past history of caries. a suscep. To cure caries at an early stage. Jiyao status. the for individuals. and plaque levels of an indi. together with definite efficacy. . caries of an individual by combining analysis demiological studies show that caries activity is of the results of multiple risk factors to achieve not evenly distributed among the general popu. time.6. and the colonization of factorial disease. risk evaluation. micro-invasive etiological factors. including diet. The risk sure contribute to dental caries. after integrated evaluation of the factors 3. More Therefore. and the progress tible tooth surface. but the efficacy of of caries. posed. sucrose intake. is one of the effective measures. The success rate is relatively tion of plaque due to poor restoration. lation and a small proportion of people with and early treatment of individual caries. while others dling incipient caries using the remineraliza- suffer from caries because of the local accumula. tal caries among the general population. For example. The risk evaluation of dental caries predicts the risk of 1. ies to obtain the best effect. ogy of caries. while among middle-aged and treatment of dental caries. of dental adhesive restorative materials.3 The Risk Evaluation Is 7. the risk of caries dling of incipient caries has been paid among children and young people lies in deep increasing attention in the individualized pits and fissures. Taking precautions in nology to filter population at risk of caries. the appearance and development of than 60 % of dental caries occur in only 20 % a highly sensitive and specific screening tech- of the overall population. The han- described above.6. plans can be made. caries. Specific low if the individual is at a high risk of car- measures and targeted intervention should be ies.

7. Degree of tooth Parts of active Most of active tissue Active tissue lost damage Minor Severe tissue lost lost completely Common cases Incipient nonstatic Arrested caries Arrested or Pulp exposed Total cavitation caries chronic deep because of caries or or total caries involving trauma dislocation pulp accidentally Common filling Pit and fissure Filling after Removing Pulp capping.7 Biological Treatment implanting teeth cultivated in vitro instead of Methods traditional implants or dentures to restore miss- ing parts of teeth or by conditioning the Nowadays. These ideas and studies provide an exciting final effect. second. or inactivated strains constructed by gene inducing the production of a new tooth structure . achieving the help us to realize the goal of the self-repair of goal of regeneration of tooth tissue by mimicking tooth damage. However.1 Restorative Therapy Based Classifying tooth-filling restoration technolo- on Tissue Engineering gies by the degree of tooth damage may predict of Tooth Regeneration the indication for tissue engineering-related tech- nology in the restoration of tooth damage. there are two directions of research into microenvironment of tooth damage in situ can the regeneration of tooth tissue: first.7 Clinical Management of Dental Caries 127 7. The The development of tissue engineering for tooth chart below summarizes accessible traditional regeneration has made the self-repair of dental filling restoration and the possible tissue engi- damage. inducing the regenera- of tooth restoration includes terminating or tion of dentin through the slow release of a sus- avoiding the progress of caries by replacing the tained release carrier into dental tissue by adding composition of oral microbes with lower-toxicity various growth factors to the filling materials. By directly ferent degrees. root Implant or restoration at sealant or filling removal of softened dentin canal treatment or restoration after present after removal of lesion fractionally or tooth extraction debridement lesion pulp capping Possible tissue Replacement Inducing the Promoting Reconstructing Implanted teeth engineering therapy by pulp–dentin regeneration of missing pulp and induced in vitro technology constructing complex to pulp tissue and hard tissue of the to restore missing lower-toxicity or defend outer repair of dentin tooth by implanting teeth inactivated strains stimuli and structure using stem cells using genetic produce growth factor engineering reparative technology to dentin using change the growth factor composition of the oral microbe Application of tissue engineering in the field engineering technology. realizing the porting the introduction of the specific technol- regeneration of tooth tissue by cultivating stem cells ogy of tissue engineering into the field of in scaffold material using tissue engineering meth. including cavitated and noncavitated. possible. tooth-filling restoration. biomineralization through the design of organic There is currently no direct evidence sup- matrix using bionic theories. lots of related reviews future for restorative dentistry [8]. 7. neering technology against tooth damage of dif- or even missing teeth. or related reports on the ods. have pointed out that tissue engineering may promote tooth filling treatment under specific circumstances.

designing organic matrix to Ltd conduct biomineralization using bionic theories 5. materials.128 L. 4. 2002. Remineralization. damage in situ. toward the highly densely arrayed and regular pulp capping. in vitro studies to 7.7. assembly of the supermolecule develops. 2008. Minimal However. and ceramics Fundamentals of operative dentistry. tissue using a bionic methods has been a hotspot Dent Clin N Am. et al. Anusavice KJ. 8. 2009. but related biosecu. deeper and frontier science such as the self- rity problems. Wilson N. 1997. New developments in dental adhesion.47:123–36. removal of a 3. metal. Schwartz RS. Control of polymerization shrinkage simulate the biomineralization of enamel and stress in resin composite restoration.51:333–57. Jiyao by implanting multifunctional stem cells for teeth tooth tissue mineralization in situ. and rela. Chen Y. Int J Stomatol. Perdigao J. aging of the materials. of current studies. fracture toughness remain. Fedorowicz Z. Analysis of mentation of hydroxyapatite and are going deeper pulpal reactions to restorative procedures. and future therapies. composite resin. Adhesively erating new tooth tissue where the tooth tissue is bonded versus non-bonded amalgam restorations for damaged in situ has become the dream of dental dental caries. Dunne SM. For example. Therefore. et al. 2009. At present. 2nd ed. while the exploration of forming enamel through the method of filling. we are trying severely cavitated or severely damaged by to implement the mineralization procedure. Tyas MJ. Published by John Wiley& Sons. Windsor LJ.35(4):393–5. and the lack of Project 1–97. 6. Nasser M. 7. Current materials and tech- may enable us to regenerate teeth. the natural caries repair process – the need for new approaches. will finally implement the restoration of tooth ods to improve prognosis. technological problems. Silver amalgam. Crit Rev Oral Biol structures such as enamel. Int Dent J. on the surface of dentin continues. Summit JB. Chicago: Quintessence Publishing Co Inc.21(1):4–7. 2007. Adv large amount of tooth tissue during surgery Dent Res. Robbins JW.13:509–20.50(1):1–12. Gainsford ID. Frencken JE. Smyth TW. in trauma. Zhou L. 2001. When it comes to Med. regen. .(4):CD007517. 2. causes the patient a lot of pain. niques for direct restorations in posterior teeth. 2000. Int Dent J. and implanting tooth tissue cultivated which crystal grows layer by layer in a well- in vitro to restore the integrity of dentition for organized way and closely controlled by organic teeth that are missing or that cannot be restored matrix. research into bionic materials to simulate tooth I. Murray PE. are the main materials in clinical application. It seems that we can only rely highly bionic in form and function and that we on the optimization of traditional treatment meth. we tively high costs have limited its possibility of believe that we can obtain tooth tissue that is wide deployment. Cochrane Database Syst Rev. As studies on Tissue engineering has provided an exciting the forming mechanism of enamel and dentin go future for tooth restoration. FDI commission leakage. Nowadays. Also. Featherstone JD.2 Restorative Therapy Based References on Bionics 1. Therefore. dentin have enabled simple nucleation and sedi. et al. insolvable problems such as margin intervention dentistry – a review. scholars.

Ling (*) 1.1007/978-3-662-47450-1_8 . almost as early as history of Dr. the oral cavity) is usually called focal infection. West China Hospital of Stomatology. Sichuan University. Tao 4. disease progression. oral [2. In a sense. and it may be a dis- rors of health and disease. 3]. Poor oral health causes disability. In other words. Sichuan University.com common risk factors. Oral health issues and major diseases share e-mail: wszouling@gmail. and develop. tics. supports and being and a determinant of quality of life [1]. oral disease can contribute to health status. signs of skeletal changes such as those occurring As Hani T. Endodontics. the research group gested since early times. Dental Caries: Principles and Management. A physical examination ease of the body that happens to begin in the mouth. People’s Republic of China 3. DOI 10. a report titled obtaining blood and urine.cn biggest threats to oral health and are by far the most © Springer-Verlag Berlin Heidelberg 2016 129 Z.” the mouth and face are mir. Recently. Imaging of the oral and craniofacial other more harmful diseases that can seriously structures (x-ray.edu. reflects the health of the entire body [4]. SPECT) may provide early affect the quality of life [5]. General health problems may cause or worsen Department of Preventive Dentistry. Xuedong (ed. a totally noninvasive Its origin can probably be traced back to the time biofluid without the limitations and difficulties of of Hippocrates” [6. MRI. oral health refers to the health is fundamental to overall health and well. and hard tissues of the mouth. David Wong from UCLA has initiated a itself. the case for action” from Dental Health Services peutic monitoring is a highly desirable goal Victoria summarized that oral health and general health are related in four major ways: Z. 2. health of our mouth and. Fadel from University of with osteoporosis and musculoskeletal disorders Gothenburg wrote in his doctoral thesis. Chengdu. ultimately. in tific and translational frontiers of salivary diagnos. oral health conditions. Dental Caries and Systemic Diseases 8 Zou Ling and Hu Tao As stated by World Health Organization. between oral and general health has been sug- mental disorders.. According to “Oral Health in America: A Report of oral disease is not just a minor ailment of the soft the Surgeon General. For example.). People’s Republic of China Dental caries and periodontal disease are the two e-mail: hutao@scu. The potential use of saliva. Poor oral health is significantly associated Department of Conservation Dentistry and with major chronic diseases. of the mouth and face can reveal signs of general If left unchecked. for oral and systemic “Links between oral health and general health – disease detection. H. and thera.g. congenital. The concept of local or systemic diseases series of concerted efforts to spearhead the scien. Chengdu. secondary to a localized chronic infection (e. “the link and salivary. 7]. West China Hospital of Stomatology. neoplastic.

the oral cavity can indeed serve as a reservoir According to another study. extractions for caries in under-21-year-olds. It can cause tooth loss. Its effect on the immune system and dentin to reach the pulp. Ling and H. In 2012. Their study (c) Cavitations (infected extraction sites) included a total of 2. unlike isms. increasing evidence over the than periodontitis at all ages over 20 years in past 30 years suggests that. pro. according to Thomas McGuire. ing digestion. and viral species. Untreated decay can is directly related to the extent. In addition to bacterial organ. Interestingly. It is well accepted that our that has access to the systemic body.130 Z. evidence. periodontal disease. or rheumatoid arthritis or principal reason for loss of all tooth types apart having corticosteroid or other immunosuppressive from lower incisors which were extracted mainly treatment [12].2 % participants had tooth loss due to caries [18]. hypothesized that chronic infections in but a few studies revealed that a greater propor- the mouth caused systemic diseases [9]. again affect- affect general health. 20 % due to periodontal diseases. Most studies supported that focal sepsis. it can ing those linked to dental caries and periodontal interfere with the mastication process and thereby disease but also including systemic diseases that affect digestion. The latest study also proved (a) Periodontal disease that dental caries and its complications were the (b) Infected root canals leading reasons for extraction. tive study evaluated the prevalence and factors tionship between oral infection and systemic dis. it can body is negatively affected by infection of any kind. The results general health are: showed that 62. and duration of become so advanced that the tooth must be the infection [5].620 teeth extracted from (d) Other diseases of the oral cavity. The main difference is that. the theory other causes [14. although lacking empirical scientific dental caries was the main cause for tooth loss. Clearly. when mation in distant body sites. For example. 70 % of tooth loss is due to tooth decay. The highest rate (36. the most impor. It has been well proven that the list. especially in immuno. the the effects of periodontal disease [5]. It was reported that caries was discredited and largely ignored for many years accounted for a higher proportion of extractions [11]. although there is an for systemic dissemination of pathogenic bacteria increase in orthodontic extractions or a decline in and their toxins. dental caries can have an effect vast flora in the entire human body. on a person’s overall health. 174 females) tant of oral diseases in regard to their impact on between 19 and 53 years participants. 1968 and only up to 45 years of age in 1988 [16]. 15]. Moreover. not only includ. such as oral 1. contribute to systemic health problems. extractions from the population as a whole are compromised hosts such as patients suffering from considered. cal diseases by penetrating through the enamel tions and diseases. the most common causes of pulpitis and periapi- tem and diminish its ability to deal with other infec. Tao common oral infection diseases in the United States “Dental caries” cannot be directly found in this and Australia [8]. tion of tooth extractions were due to periodontal cept has been neglected for several decades and still disease. a quantita- Most studies stated above concerning the rela. due to dental bactere. but its no matter where it is located. especially in patients over 40 years old. The con. for periodontal reasons [17]. There were 457 adult (283 males. were extracted without evidence of infection. dental caries is not an infection tozoal. greater its potential for affecting systemic health. and 10 % due to thereby providing no relief of symptoms. dental caries is one of Infection can also seriously stress the immune sys. related to tooth loss due to dental caries among eases are related to periodontal disease [13]. Since many teeth Overall. And workers in industrial estates in central Thailand. mia. caries and its sequelae remain the malignancies. diabetes. type.382 patients. oral microorganisms can include fungal.9 %) of cancer [5] extraction occurred for those of 41–60 years of . Thomas McGuire explained the reasons as the oral cavity contains some of the most varied and following: certainly. the more effects on overall health are significantly less than serious the infection and the longer it is present. Over 100 years ago the theory of removed (extraction). leading to infections and inflam. is a subject of controversy [10]. As mentioned before.

third-molar surgery. ganisms [23]. the mouth plays as a portal of entry for infection.4 %. The oral cavity is intensely colonized by bac- tionship between dental caries and general health. the immune response to the bacteria can tal disease was 14. and 55 % of patients after bilateral tonsil- next discussing dental caries and immune system lectomy. sum- ment [21]. scaling. caries was still the spread to other parts of the body (which is called main reason for extraction even in elderly patients. anaerobic incubation. cardiovascular disease. a potentially life- tooth impaction were 13. from the original site of infection. Although 86 % of threatening condition which has a relatively high teeth extracted for periodontal disease were in mortality rate. and respiratory infections. Following this introduction and over. ganisms [11]. metastatic injury through a wound or infection or through a surgical from the effects of circulating oral microbial tox- procedure or injection when other foreign bodies ins. As early as 1990.1 Dental Caries induce bacteremia detectable by means of blood and Bacteremia cultures in a variable percentage of subjects [24]. has been well documented. dental scaling. Their results showed that view. diabe. third-molar surgery. Transient bacteremia is produced tes mellitus. hematogenous spread). Bacteria can also use the blood to patients over 40 years of age. and bilat- and concludes with studies that are associating eral tonsillectomy by means of lysis filtration of oral infections with serious systemic diseases and blood samples with subsequent aerobic and conditions. Our goal of this chapter is to discuss the rela. and other conditions caused by ous frequencies following dental procedures and dental caries directly are also included [20]. The blood is normally a sterile environ. root different phyla [22]. Tooth loss due to caries was 51 %.9 %. Even daily life activities such as eating. describes the role remia after dental extraction. And anaerobic microorganisms were disease and kidney diseases. overall quality of health and well-being has not have shown that the oral cavity is inhabited by been well studied. or using toothpicks also 8. studies associating systemic dis. chewing gum. the remainder of the chapter is organized as bacteremia was observed in 100 % of patients follows: first defining dental caries and bactere. tooth loss. after dental extraction. cases. and metastatic inflammation caused by are entering the arteries or veins. This chapter explores what the dental caries Heimdahl et al. head and neck cancer. causing infections away but to a less degree than in younger ones [19]. been proposed for several years [6]. and children growth. and supernumerary and cause sepsis and septic shock. endodontic treatment. in order to enrich the content more than six billion bacteria representing in of this chapter. brushing the teeth. This may occur result of transient bacteremia. 20 % of patients after endodontic treat- sclerosis.8 Dental Caries and Systemic Diseases 131 age. teria. Three mechanisms or pathways linking oral Bacteremia is an invasion of the bloodstream by infections to secondary systemic effects have bacteria. Bacteremia may immunological injury induced by oral microor- cause no symptoms and resolve without treat. Li et al. or it may produce several consequences like Till now. excess of 700 species belonging to at least nine eases with periapical diseases. In some the connection between the dental caries and . So the detection of bacteria in the marized the mechanisms as the following: meta- blood (most commonly accomplished by blood static spread of infection from the oral cavity as a cultures) is always abnormal. and heart attack. Since the effect of dental caries on the approaches such as 16S rRNA gene sequencing. ment. and last describing isolated more frequently than aerobic microor- dental caries and gastrointestinal diseases. periodon. ment. Bacteremia occurs with vari- canal treatment. Recent advances in bacterial identification we will summarize the limited recent advances in methods. particularly culture-independent this topic. there is no direct evidence to prove fever and other symptoms of infection. not only as a result of dental manipulation. 70 % of patients after dental then briefly describing dental caries and athero. 55 % of patients after mia. detected the patients with bacte- can reveal about general health.

presented identical phenotype and genetic charac.g. 26]. The baseline is that there were no infection. through and dietary changes [29]. an electri. such as Streptococcus are the three most common modalities used in sanguinis [10]. The results found that regions of France. an immuno. the oral soft and hard tissue. Mohammadi et al. they also been associated with the initiation of dental caries. but we can find some clues from 8. Hong Kong. class V pressant therapy) may bring a person in contact dental caries of posterior teeth were evaluated in with new types of bacteria that are more invasive three intervals: before treatment. their function are detrimental to the hard tissues cal barrier that reflects the Eh difference between in the oral cavity. 3 weeks after than those already residing in that person’s body. In the oral cav. a shift in oral flora toward cariogenic bacteria.g.1 Dental Caries and Head endodontic treatment back to the root canal. Italy. [27]. by an overt breach in the physical system (e. Their . the initiation of the treatment. the Indian sub- microorganisms from the root canal and blood continent. AIDS). negatively impact the normal head and neck The results not only illustrated that dental caries is structures surrounding the tumor. and at the end of further increasing the likelihood of bacterial the treatment.. Despite their Streptococcus sanguinis are most consistently effects in eradicating the tumor. and Brazil and among African Americans teristics within the patients examined. The blood of 550. [31] increased frequency and severity [25. either used singly or in combination. Spain. demineralization. Radiation caries is mainly an the host cell and the microbial layer. Of these cases. Ling and H. as they are kept in check by the body’s natural Firstly. central and eastern Europe. which are host-derived peptide antibi. undergoing radiotherapy. Surgical resec- the most common cause of pulpitis and periapical tion removes abnormal tissue. isolated from the blood. and indirect damage These bacteria are normally harmless as long may also arise from systemic toxicity. used phenotypic and Neck Cancer and genetic methods to trace microorganisms released into the bloodstream during and after 8. organisms can propagate initial caries usually occur around the third week and cause both acute and chronic infections with of treatment [30]. medical treatment (e. Debelian et al. Hyposalivation leads to accelerated dental [25]. in the oral mucosal epithelium. trauma) or immunological barriers (e. Tao bacteremia. radiotherapy. In reviewed 27 cases with head and neck cancers addition.and diseases but also showed a clue that cariogenic chemotherapy frequently cause direct damage to bacteria may be related to bacteremia.. Surgical resection. once the equilibrium is disturbed caries through changes in salivary composition.. immunosup. and any disturbances in otics. and Neck Cancer Treatment Microbiological samples were taken from the root canals of 26 patients with asymptomatic apical Head and neck cancer accounts for more than periodontitis of single-rooted teeth. in the Unites States.2.g. Mouth and tongue cancers onstrated that endodontic treatment can be the are more common in the Indian subcontinent cause of anaerobic bacteremia and fungemia. because radiation caries is a common disease in ity there are several barriers to bacterial penetra. some cariogenic bacteria were also motherapy. and the salivary gland tissue that result in hyposalivation reticuloendothelial system (phagocyte barrier) [28].000 cases annually worldwide. Salivary glands are very sus- defensins. We all know that saliva in the oral cavity tion from dental plaque into the tissue: a physical protects hard tissues against acid attacks and barrier composed of the surface epithelium. The inci- the patients was drawn during and 10 min after dence rate in males exceeds 20 per 100. However. ceptible to radiation. Streptococcus mutans and head and neck cancer treatment. clinic.which dem. class V decays prior to radiotherapy. indirect effect of irradiation-induced changes in logical barrier of antibody-forming cells. while radio.2 Dental Caries and Head published papers. we will discuss the radiotherapy barriers and the immune system. It is reported that the neutropenia. and che- Interestingly.132 Z.000 in endodontic therapy.

is the most common cause of dental car. Dentistry and Maxillofacial Prosthetics at Dental caries was assessed by the present (Y/N). and Neck Squamous Cell uate the effects of new techniques such as inten. mous cell carcinoma (SCC). we talk about which one of the tooth decay are linked to an immune response. mucosal surfaces may protect the host against apy.3 %. Carcinoma sity-modulated radiotherapy on occurrence of dental caries. three modalities.8 Dental Caries and Systemic Diseases 133 results found that mean percentages of class V ignored. Surgery showed that the bacteria that caused Secondly. was ana- overall prevalence of dental caries was 28. Roswell Park Cancer Industry between 1999 and DMFT/dmft. Finally. We because of the need to frequently consume could think of dental caries as a form of ‘collat- highly cariogenic dietary supplements for weight eral damage’ and develop strategies to reduce its maintenance or are taking sucrose-rich medica. while patients who were post-radiotherapy and those 102 (25.02. The results of who were post-chemotherapy and post-radio. in which a higher dose is beamed Recently. 146 (36. particu- able. either used singly or in combi. risk while preserving the beneficial effects of the tions. respectively. dose rate. In addition. [28. the authors 8. and amount of salivary tissue irradiated. Their results showed that the weighted larly their history of dental cavities.8 %) patients. which may be protective against cancer [34]. the caries 3 weeks after radiotherapy and at the end DMFT index is expectedly highest in patients of radiotherapy were 28. and was determined from 19 studies. respectively.4 %.2 Dental Caries and Head also pointed out that further studies should eval. In order to determine the NY. The authors explained that “Caries is a prior to radiotherapy versus those being prepared dental plaque-related disease. conducted a systematic literature squamous cell carcinoma (HNSCC). the study overall showed that those who had high therapy were 24 and 21. The study search with assistance from a research librarian involved 399 patients newly diagnosed with in the databases MEDLINE/PubMed and HNSCC and 221 participants without the cancer Embase for articles [33].41 and who were post-radiation therapy compared to 67.1 % lyzed by measuring the number of decayed. an interesting paper published online at the tumor site without increased received dose in JAMA Otolaryngology – Head and Neck of the surrounding tissues [31]. Lactic acid bacte- for chemotherapy. The presence of these children undergoing hematologic malignancies otherwise beneficial bacteria in saliva or on who were treated largely by curative chemother.2. .6 %) had oral cavity squa- who received only chemotherapy was 37. In contrast to the caries prevalence. These findings are patients who were post-chemotherapy and in accordance with the results of other studies healthy controls [33]. The researchers from the University at Buffalo. Oropharyngeal The weighted prevalences of dental caries in SCC occurred in 151 (37. The missing. Of the 399 patients weighted prevalence of dental caries in patients with HNSCC. The cavity numbers were less likely to have HNSCC. authors attributed the discrepancy to the distinct compared with participants who had low cavity differences in the dental management of patients numbers. They could have higher caries activity chronic inflammatory diseases and HNSCC. 2007. and filled teeth.05 % ± 19. 64 published who were all selected from the Department of papers between 1990 and 2008 were reviewed. ies after therapy. nation. 32]. The dental history of all patients. their oral hygiene may be lactic acid bacteria” [34].42 % ± 14. link between dental cavities and head and neck Catherine et al. Another explanation for the ria cause demineralization (caries) only when unanticipated caries prevalence may be because they are in dental plaque in immediate contact 12 of the 19 studies included were carried out on with the tooth surface. and DMFS/dmfs indexes if avail. Since the severity of xerostomia is related to the radiation dose.6 %) had laryngeal SCC. set out to determine if there is a significant prevalence of dental caries in cancer survivors.

found that As previously mentioned. miologic studies regarding the potential associa- tion of tooth loss with head and neck cancer risk have been published nowadays [35–38]. The 8.3 Tooth Loss and Head Europe. Oral streptococci. when missing teeth were more and Neck Cancer Risk than 15 in number. espe- best use of all the information we have gathered cially S. On the other hand. and by statistically ing dental caries. as high as 90 % in some countries according to sistent conclusions yet. but 5. But the answers have not reached con. a quantitative and systematic Alcohol is one of the main risk factors for oral summary of the evidence using rigorous methods cancer. the evidence still remains contro- versial. However. This allows us to make the normal oral microflora. we will such an association. Ling and H. some evidence between caries and cancer from cantly increased risk of head and neck cancer by another side. Later. Guha et al. Furthermore. oral streptococci were association of tooth loss with head and neck can. Actually. observed that the report of World Health Organization (WHO) missing 6–15 teeth increased the odds ratio of [43].2. Current evidences . but it is is necessary.3 Dental Caries and Children authors also summarized that several plausible Growth mechanisms may explain why a significant increased association of tooth loss with head and There’s no doubt that dental caries constitutes the neck cancer was observed in their analysis. some Neisseria strains are found to be ment effect and assess whether treatment effects able to produce significant amounts of acetalde- are similar in similar situations. dental decay is esophageal squamous cell carcinoma by more five times as common as asthma and seven times than twofold in both Latin America and central as common as hay fever [44]. the mod- erate [6–15] tooth loss was associated with a 45 % increase in the risk of larynx cancer. Tao 8. Neisseria strains are University conducted a meta-analysis involving considered to be part of the normal oral flora. suggesting that tooth loss is include the relationship between tooth loss and probably an independent risk factor of head and tumors in this chapter. hood: as many as 60 % of school children have tor of head and neck cancer is an interesting experienced dental caries.to 17-year-olds. Alcohol itself is not carcinogenic. and Neisseria strains are related combining the results of similar studies. mutans. Among 5. neck cancer [39].2. single most common chronic disease of child- Whether tooth loss is an independent risk fac. About a decade improve the precision of our estimates of treat. Therefore.204 patients and 5. probably via their high alcohol dehydroge- Chinese researchers from Guangxi Medical nase (ADH) activity [41]. and the data can reach question. Wang et al. 8. caries is one of the moderate and severe tooth loss did not change most common reasons of tooth loss. risk of oral cancer [42]. multiple epide. in 2007. are the primary pathogens caus- in our systematic review. Their overall estimates provided individual variation of salivary acetaldehyde lev- evidence that tooth loss was significantly associ. we can to the early stage of caries. no increase risk was observed [40].4 Cariogenic Bacteria and Oral sidering the modest sample size and different Cancer study designs.134 Z. some hyde. Recently.518 controls to assess the they are found only in low numbers in the oral inconsistent results from published studies on the cavity. 18 and 54 %. We know that meta-analysis is the oxidized to carcinogenic acetaldehyde in saliva use of statistical methods to combine results of by the ADH enzyme of some oral microbes of the individual studies. before. els after alcohol drinking and thereby also to the ated with increased risk of head and neck cancer. proved to contribute significantly to the normal cer risk [39]. respectively. the moderate [6–15] tooth loss and of cariogenic bacteria on oral cancer provides the severe (>15) tooth loss experienced a signifi. But con. We believe that the effect In addition.

there is a statistically significant gain in BMI SDS and a relationship between dental caries and childhood small gain in height SDS [58]. in young children. Based and sleeping habits. and were measured prior to extraction using standard gastrointestinal disorders. Caries of the primary teeth or ceive these sugary products as non-beneficial. toothache and infection alter eating foods and beverages in urban areas [48]. Moreover.and six-year-old children who may be one of the reasons [49]. Another retrospec. growth will be better. and metabolic on the recent studies. In their another obesity [51. social. the eating of some foods will cause pain. [55]. Five. the children’s of the primary or permanent dentition (55 %). criteria and a single trained examiner.8 %) children [46]. A recent This is a significant side effect of childhood car- descriptive cross-sectional study assessed dental ies that is widely acknowledged by the experts. On the other have undiagnosed and untreated diseases coupled hand. high-fat food. A recent study found a positive correlation tive cohort study gave support to the idea that between severe early childhood caries (S-ECC) children who lived in urban areas showed 75 % and body mass index (BMI) of 3. 52]. In addition. children [56]. pants had a mean dmft of 7. and potential to thrive line. and height chewing problems. and environmental factors [45]. pain. dietary intake. Malek et al. 30 years ago [54]. While most people child’s body weight was firstly noticed by Miller in rural areas in Zimbabwe cannot afford and per. may thereby avoid certain nutritious foods and dence. Kay et al. In 2009. lence of dental caries in both urban (59. Specifically.27) at base- mance. children with increases in weight and height than those without . The tal caries can lead to infection. is essential to remember that dental caries is one dren from low socioeconomic status background of only very few common childhood diseases attending public primary schools in Zimbabwe.5 %) and The relationship between dental caries and rural (40. For example. behavioral. ine whether the removal of carious teeth affected educated and low-income families that pay less children’s growth relative to that of a standard attention to the dental hygiene of their children population. Low. This disparity between urban and rural chil.and 6-year-old greater probability of presenting caries when children. den. weight. some of the patients been shown to be a major risk for caries inci. access and consumption of high sugar-containing therefore. The partici- which in turn may affect his or her school perfor. which cause large numbers of the child popula- The results showed that there was a high preva. which means the mean BMI of S-ECC compared to those children residing in rural areas children is significantly more than the caries-free [47]. general anesthesia took apart in this study.8 Dental Caries and Systemic Diseases 135 show that dental caries is a multifactorial disease extensive dental caries may need to undergo and complexly modulated by genetic. con- compared to those whose family incomes are ducted a longitudinal clinical trial study to exam- greater than 200 % of the FPL (31 %). socioeconomic status has processes [57]. treatment under general anesthesia in hospital. abscesses. Children living in poverty represent a select high-calorie. It caries experience among 12-year-old school chil. Dental caries can also contribute longitudinal birth cohort. But if such bad oral than the federal poverty level (FPL) show decay condition has been changed. ability to learn.18 (SD 3. attended for extraction of carious teeth under Apart from structurally weakening teeth. tion to undergo general anesthesia. and they ies can damage a child’s sense of self-esteem. “early childhood caries” (ECC) is one of the most affording them is often considered as a symbol of prevalent health problems in infants and toddlers higher socioeconomic status. and at follow-up children showed a [50]. poor nutritional status. some patients cannot pulverize the foods with limited access to care. well and may have an adverse effect on the inter- portion of US children with family incomes less nal absorption of nutrients. serious car. We know that if caries involve the dren has been partially attributed to increased pulp. were then remeasured 6 months later. found that to poor nutritional status and affect the growth of children who had caries at 61 months had slower adult teeth [53]. Nearly twice the pro. children’s dental caries levels. which is recog- large population of high-risk individuals who nized as risk factors for obesity.

136 Z. Ling and H. Tao

decay at the same age [59]. These observations BMI distribution. And they also recommend that
were consistent with a recent study which exam- future research investigate the nature of the asso-
ined the association between untreated dental ciation between body mass index and dental car-
caries in primary and permanent teeth with age- ies in samples that include a full range of body
adjusted height and weight among 6–12-year-old mass index scores and explore how factors such
children in Bangladesh [60]. as socioeconomic status mediate the association
However, the relationship between dental car- between body mass index and dental caries [62].
ies and child’s growth is inconclusive so far. A
research from the department of cardiology,
endodontology, and pedodontology in Academic 8.4 Dental Caries
Centre for Dentistry Amsterdam (ACTA) has and Atherosclerosis,
been published in Clin Oral Investig in 2011. The Cardiovascular Disease,
study has two objectives: first, to assess the rela- and Heart Attack
tion between dental caries and body proportions
cross-sectionally in a Suriname caries child pop- Atherosclerosis (also known as arteriosclerotic
ulation and, second, to investigate whether dental vascular disease or ASVD) is a specific form of
treatment had a significant influence on body arteriosclerosis in which an artery wall thickens as
growth of these children in a randomized con- a result of the accumulation of fatty materials such
trolled trial using different treatment strategies. as cholesterol and triglyceride. Cardiovascular
Three hundred eighty 6-year-old children with disease (CVD) is the broad term used to categorize
untreated dental decay participated in the study. any abnormal condition characterized by dysfunc-
Participants were evaluated after 6 months and 1, tion of the heart and blood vessel system, princi-
2, and 3 years. However, negative correlations pally referring to cardiac disease, vascular diseases
were observed between anthropometric measures of the brain and kidney, and peripheral arterial dis-
and the number of untreated carious surfaces and ease. Evidence suggests a number of traditional
caries experience of the children. Next, no sig- risk factors for atherosclerosis and CVD: age, gen-
nificant differences in growth pattern between the der, high blood pressure, high serum cholesterol
treatment groups were observed. Thus, the levels, tobacco smoking, excessive alcohol con-
authors suggested that caries activity is a negative sumption, sugar consumption [63], family history,
predictor for body growth in children, and dental obesity, lack of physical activity, psychosocial fac-
intervention does not show significant improve- tors, diabetes mellitus, and air pollution [64].
ment within 3 years [61]. Later, Merrilyn et al. However, these factors cannot explain all the
undertook an updated systematic review of the deaths from CVD. For example, about 40 % of
relationship between body mass index and dental coronary heart disease (CHD) deaths occur in peo-
caries in children and adolescents. The authors ple with cholesterol levels that are lower than the
searched MEDLINE, ISI, Cochrane, Scopus, population average [65]. Therefore, medical
Global Health, and CINAHL databases and con- researchers’ attention has focused in recent years
ducted lateral searches from reference lists for on identifying additional risk factors that are non-
papers published from 2004 to 2011, inclusive. traditional but may play major roles in explaining
Finally, a total 48 studies were included. Three some of the variability in atherosclerosis and CVD
main patterns of relationships were found risk.
between dental caries and BMI: 23 of the 48 During the last three decades, there has been
studies found no association between BMI and an increasing interest in the impact of oral health
dental caries, 17 found a positive relationship on atherosclerosis and subsequent cardiovascular
between BMI and dental caries, and 9 found an disease (CVD). Just as Meurman et al. wrote in
inverse relationship. The reasons that authors their paper which was published in Crit Rev Oral
analyzed may be method of dental examination, Biol Med: “chronic infections caused by a variety
sample differences, dental caries prevalence, and of micro-organisms are thought to be involved in

8 Dental Caries and Systemic Diseases 137

the etiopathogenesis of CVD by releasing cyto- not the only reason that makes it noteworthy.
kines and other pro-inflammatory mediators that Actually, the 9,760 subjects included in this work
may initiate a cascade of biochemical reactions make it the largest sample size of its kind at that
and cause endothelial damage and facilitate cho- time. Since then, investigating the relationship
lesterol plaque attachment. Yet, due to the multi- between dental disease and CVD has become a
factorial nature of dental infection and CVD, priority.
confirming a causal association is difficult, and Later, in 2001, a prospective cohort study in
the published results are conflicting. The main Stockholm, Sweden, followed 1,393 individuals
deficit in the majority of these studies has been for 27 years and concluded that oral health was a
the inadequate control of numerous confounding risk factor for death due to CVD, especially in
factors, leading to an overestimation and the combination with smoking, another risk factor.
imprecise measurement of the predictor or over In this investigation, a significant correlation
adjustment of the confounding variables, result- between caries and death due to CVD when
ing in underestimation of the risks” [66]. adjusted for age and gender was demonstrated,
indicating that this possible etiological pathway
should be further investigated in the future. And
8.4.1 Dental Caries the number of tooth surfaces with caries and pres-
and Atherosclerosis ence of plaque were significantly increased for
and Cardiovascular Disease smokers compared to nonsmokers [69].
Maharaj and Vayej studied 44 black patients
Many studies have looked at poor dental care as a with severe rheumatic heart disease before they
risk factor for cardiovascular disease (CVD). The had cardiac surgery in 2012. Abnormalities were
results have been inconsistent, but most studies detected in the panoramic radiographs of 84.1 %
support a modest association between them [67]. of patients. The most frequent lesion was caries,
Mattila et al. may be one of the first researchers present in 56.8 % of patients, followed by miss-
to indicate a relationship between orofacial infec- ing teeth in 54.5 %, and impacted teeth in 25 % of
tions and cardiovascular disease. In 1989, they patients. Retained roots were present in 22.7 %
published an article in British Medical Journal and periapical pathology was detected in 18.1 %
(BMJ) and reported that there was an unexpected of patients [70].
correlation between dental disease and systemic It is clear that minimal carious lesions, caries
disease. After adjusting for age, exercise, diet, with and without involvement of the pulpal cavity,
smoking, weight, blood cholesterol level, alcohol and chronic apical periodontitis (CAP) represent
use, and health care, people who had caries and different stages of the same inflammatory pro-
periodontal disease had a significantly higher cess. A recent study shows for the first time that
incidence of acute myocardial infarction [68]. dental caries, pulpal caries, and chronic apical
Another prospective cohort study, published in periodontitis are associated positively, while res-
1993, found that patients with periodontal dis- torations are associated inversely, with aortic ath-
ease had a 25 % increase in CVD, and men erosclerotic burden [71]. The authors’ result
younger than 50 years had a significantly higher showing that not only CAP but also caries with
risk. However, no association between extent of pulpal decay or no visible pulpal decay was asso-
active dental decay and risk of coronary heart dis- ciated with a greater atherosclerotic burden was
ease was observed. Since tooth loss in people somewhat surprising. We know that early stage of
under 60 is usually caused by dental caries, the caries is an inflammatory process localized in the
authors said they cannot rule out the possibility oral cavity that does not affect the pulpal cavity or
that the increased risk of coronary heart disease the bone, indicating that a lesser extent of associa-
among young men with no teeth may have been tion of the early stage of caries with the athero-
related to previous dental decay [69]. These sclerotic burden was expected than with the other
important discoveries resulted from the study is two serious stages. One obvious explanation for

138 Z. Ling and H. Tao

this finding may be the covariance of these fac- protein (CRP), interleukin-6 (IL-6), and tumor
tors, as pulpal caries and CAP occur primarily in necrosis factor-α (TNF-α) [75]. Bacterial species
patients with extensive tooth decay. The initial lying within the root surfaces supporting struc-
carious lesion and caries not yet affecting the tures induce systemic inflammation and immune
pulpal cavity exist for a longer period compared response, thereby increasing levels of serum CRP
with the pulpal decay, which can precede pulpal and serum IgG. In 2011, Kaneko et al. conducted
decay by a number of years. An explanation other a longitudinal study to elucidate the relationship
than the disease lasting many years is that even between root caries and the onset of dysrhyth-
forms of caries not yet involving the pulp are not mias on electrocardiographs in community-
merely local inflammatory lesions but rather dis- dwelling persons aged 75 and older. Serum CRP
ease affecting the entire body. The authors sug- level was used as a variable to link root caries
gested that prospective studies are required to with dysrhythmias directly. They found that a
confirm these observations and answer the ques- high mean CRP serum level group had a signifi-
tion of possible causality [71]. cantly higher number of sites with root caries
than a low CRP group. Moreover, number of sites
with root caries events was significantly associ-
8.4.2 Root Caries and Cardiac ated with cardiac dysrhythmia among nonsmok-
Dysrhythmia ers. These results confirmed that root caries is
and Gerodontology related to the incidence of dysrhythmias in non-
smokers [73].
Cardiac dysrhythmias, especially atrial fibrilla-
tion, are known to cause ischemic heart disease.
Many studies suggested that inflammation plays 8.4.3 Streptococcus mutans
a prominent role in the onset of atrial fibrillation and Atherosclerosis
[72]. With respect to the result of logistic regres-
sion analysis, cariogenic bacteria have a specific We know that Streptococcus mutans (S. mutans)
impact on the pathogenesis of cardiac diseases, is a major cariogenic pathogen that is a normal
especially dysrhythmias [73]. In 2005, research- inhabitant of the oral cavity in most individuals.
ers from University of Copenhagen designed a S. mutans has also been isolated from the blood
cross-sectional study to examine whether caries of patients with infective endocarditis (IE), which
is associated with cardiac arrhythmias in strongly suggests a close relationship of the
community-dwelling people aged 80 and older. pathogen with IE [76, 77]. Ullman et al. pointed
The primary finding of the multivariate logistic out that their experience agrees with the literature
regression analysis was that persons with three or and indicates that S. mutans is primarily a patho-
more active root caries lesions had more than gen in elderly patients with heart disease and may
twice the odds of cardiac arrhythmias than per- be associated with IHSS [78]. In 2006, Nakano
sons without active root caries. The findings indi- from Osaka University Graduate School of
cated that there may be a link between active root Dentistry and coworkers published the first study
caries and cardiac arrhythmias in the oldest old to analyze the presence of streptococcal species
[74]. In order to explain the link, we should turn in diseased heart valve and atheromatous plaque
to the immune response because several studies specimens, as well as in dental plaque samples
have reported that an increase in dental caries is from the same subjects by a PCR method.
associated with a heightened immune response. Unexpectedly, S. mutans was detected at high
In addition, dental caries affects the production frequencies and quantities in both heart valve tis-
of IgG and induces acute-phase proteins. The sues and atheromatous plaque samples in their
inflammatory-mediated cytokines and acute- study. Their conclusion indicated that S. mutans
phase proteins are practical markers of increased is a possible causative agent of cardiovascular
risk of cardiovascular disease, such as C-reactive disease [79]. In addition, when using DNA

The authors found that a person with fewer than 10 of their own teeth remaining is 1. the major surface protein antigen Pac [85.4 Tooth Loss the chemical composition of its cell surface sero. Furthermore. found that S. increasing epidemiological evidence linking poor tion [84]. and Cardiovascular Disease type-specific rhamnose–glucose polymers and Stroke (RGPs). mutans expressing bacteria in cardiovascular specimens” in Oral collagen-binding protein (CBP) is a potential Microbiology and Immunology. When it comes to the possible up period (1976–2002) that presents for the first reasons of the link between S. mutans isolated 2. The results found that patients whose dental plaque specimens were most of the Cbm-positive strains showed also positive for S. mutans and cardio. This time. the gene encod- idea that there are subpopulations of S. While some studies have shown that decay is not Serotype c is reported to be the most prevalent in a direct risk factor. Nomura and colleagues demonstrated that the mutans cells bind to extracellular matrix mol- oral isolates differed from those found in the ecules and fibrinogen with contribution from heart valve [80]. it may be summarized number of teeth and both all-cause and CVD as the following: mortality. which form a backbone of rhamnose polymers with side chains of glucose polymers. published another paper titled “Detection of oral 3. and S. mutans strain As pointed out by Watt et al. they risk factor for hemorrhagic stroke [87]. mutans were shown to induce from dental plaque and an infected heart valve platelet aggregation. followed loss. see if they play a role in S. was and CVD and that the number of teeth can be found to show low cariogenicity but high viru. The infection with S. which was higher levels of binding to type I collagen as significantly higher than any other tested species well as higher rates of adhesion and invasion when the same analysis was performed [81]. proteins. and k. capacity to interact.8 Dental Caries and Systemic Diseases 139 fingerprinting to compare S. mutans is classified into four serotypes (c/e/f/k) based on 8. with evidence showed a direct link between oral health a defect of the glucose side chain in RGPs. thrombus formation. 86]. due to alterations of several cell surface (n = 7. these findings lend credence to the positive strains. 90]. Furthermore. which presumably lead to from a patient who underwent heart surgery. may have an enhanced patients than from non-IE patients [88]. S. seven times more likely to die of coronary dis- eromatous plaque lesions is formation of foam ease than someone with more than 25 of their cells. the cells of the cardiovascular system [82]. it can and does cause tooth oral isolates at approximately 70–80 %. and possibly invade. which are macrophages that accumulate own teeth [91]. They drew the conclusion from a fairly large types. Serotype k. mutans attachment comitans. In addition. oral health with the development of chronic diseases . It was also found that S.. Recent to invade endothelial cells [82]. although there is GS-5 has been shown to enhance their forma. used to assess increased risk of CVD in adults. mutans was 78 %. Lately. mutans ing Cbm was detected significantly more carried in humans that. S. the positive rate of and invasion of human umbilical vein endo- S. while not necessarily frequently in heart valve specimens from IE associated with caries. time a dose-dependent relationship between vascular system diseases. from excess cholesterol. Three years later. Nakano et al. mutans was the most frequently two types of cell surface collagen-binding detected species in the cardiovascular specimens. Serotypes e and f have been found risk for cardiovascular disease [89. which has been demonstrated to be a greater by e. Cnm and Cbm.4. with HUVEC as compared to the Cnm- Collectively. lence in blood as compared to the other sero. prospective study with a long follow- structures [83]. One crucial step for the development of ath.647). f. mutans in cardiovascular specimens from thelial cells (HUVEC). have been studied to followed by Aggregatibacter actinomycetem.

1942 or 1952 from The Danish MONICA socioeconomic. with complete data. During 103. the number of remaining the Glasgow Alumni Cohort to investigate whether teeth was significantly lower among stroke patients oral health in young adulthood is independently in their 50s than data reported for that age group in associated with cause‐specific mortality after the Survey of Dental Diseases.871 participants and they were followed to a lesser extent. Ling and H. usually a clot. Tao and mortality. incidence of cardiovascular dis- for 8. A recent study found and all-cause and CVD deaths after controlling for that stroke patients in their 50s and 60s had signifi- a range of potential confounding factors [92]. socioeconomic. behavioral. associated with increased risk of stroke. therefore. follow up study (monitoring trends in and determi- tus [92]. 7. behavioral. strongly associated with incidence of stroke and. After adjusting for a prospective cohort study of stroke in Korea on demographic.140 Z. Moreover. there were different opinions from pitalized for other conditions in the corresponding other studies. They confirm that tooth loss is independently pared to subjects with natural teeth only. during averagely years. most previous diovascular morbidity and mortality over 5–12 studies exploring the link between tooth loss and years. It is quite difficult to rule out all CVD and 549 from cancer. When the number of common risk factors as confounding variables. however indirectly. Choe et al. samples and have failed to control adequately for 1932.432 deaths occurred among subjects lifestyle such as hypertension. Their results showed that tooth loss was PLOS ONE caught our attention. including 509 deaths from and alcohol intake. and 515 of cancer. sisted of 12. periapical lesions. diabetes. .0 (SD: 3. suggesting the pos- accounting for childhood socioeconomic back. sibility that stroke patients may have lost teeth at a ground and other risk factors in young adulthood. Thus. such as the study using the data from age groups. are also a factor in stroke risk. missing teeth and CVD mortality [93]. Heitmann and their byproducts enter a tooth’s pulp chamber. ease and coronary heart disease. particularly small but significant association between tooth loss for hemorrhagic stroke [95].5 Pulpal Periapical Diseases countries. younger age.173 person. When the number of missing teeth caries). in heart disease [5]. normally CVD compared with those with fewer than five resulting from an infected root canal (caused by missing teeth. Interestingly. The sample con. another example of how dental caries can play a there seemed to be a nonlinear relation between role. and general health sta. their recent prospective cohort study nants of cardiovascular disease) in 1987–88 and of a national sample of Scottish adults published in 1993–94. Stroke remains the third leading cause of death (after heart disease and cancer) in most developed 8. and 1. This is was transformed using fractional polynomials. edentate subjects had significantly characterize their independent effects and interac- higher risk of all-cause and CVD mortality com. association between stroke and tooth loss can be line) were traced during up to 57 years of follow‐ explained by common risk factors associated with up.000 subjects (30 years or younger at base.4. Indeed. diabetes. smoking. smoking. Cerebrovascular ischemic strokes are and Coronary Heart Diseases the commonest kind of stroke and occur as a result of an obstruction.480 cases of all-cause mortality. within a blood Endodontic inflammation occurs after bacteria or vessel supplying blood to the brain.5 years of follow-up [94]. there were 1. The authors also pointed out that the Over 12. and tooth loss to health status. Their find. these associations are still doubtful Gamborg examined if the number of remaining due to imprecise measurement of important risk teeth was associated with the development of car- factors of systemic disease. cantly fewer remaining teeth than did patients hos- However. conducted 498 of CVD. the exact mechanisms of the relationship there was evidence that students with nine or more between stroke and tooth loss are difficult to iden- missing teeth at baseline had an increased risk of tify [96]. tions. and hypertension. and hyper- ings confirm previous studies which have shown a tension does interact antagonistically. The prospective observational study systemic disease have been conducted in selected among1474 men and 1458 women born 1922. missing teeth was treated as a categorical variable.3) years.

tion. and some dis- ered relationships between chronic periodontal dis.1 Salivary Immunoglobulin A to release of cytokines into the systemic circulation and to subsequent deleterious vascular effects [98]. some Indian tions about the proposed association. ence of bacteria to the buccal epithelium and to Joshipura et al. or other comes are biologically plausible.4. Recently. they is the dominant immunoglobulin in the healthy did not reveal a significant association between end. inherited or medication disorders. about a positive self-reported history of ET in the Health the relationship between Salivary IgA and dental Professionals Follow-Up Study [100]. more direct evidence should be found to a protocol-driven cross-sectional pilot study to support this connection. Despite numerous differences between It’s no doubt that infection stresses the immune chronic inflammatory disease of periodontal and system. Gregory et al. several epidemiologic investiga. ence in the bacterial colonization. similarities. Thus. It can agglutinate oral bacteria. Dental caries is an infectious disease that Gram-negative anaerobic bacteria. It does well at interfering with the initial between pulpal inflammation and CHD.8 Dental Caries and Systemic Diseases 141 Apical periodontitis is an acute or chronic 8. in which a localized inflammatory response to bacterial infection leads 8. summarized their term disease (such as periapical abscesses).5. primarily that: (1) both conditions share should have a deleterious effect on the immune a common microbiota that often is associated with system. although colonization of caries-associated microflora on the dental caries was not associated with CHD. However. orders can affect these systems such as general ease and coronary heart disease. sparking ques. Several years later. and IgM antibodies to a Streptococcus mutans heart disease. Oral microorganisms and aerodigestive antigens Frisk and colleagues are one of the first groups who are continuously influenced by the two major anti- specifically studied endodontic variables as risk fac. However.5 Dental Caries and Immune inflammatory lesion around the apex of a tooth root System Disease which is caused by bacterial invasion of the pulp of the tooth. between the host and microbiota [101]. significantly higher levels of naturally occurring tal caries (including its subsequent pulpal salivary immunoglobulin A (IgA) and serum IgG. Caplan et al. found a possible modest association enamel. periapical diseases and tooth loss) and coronary IgA. body classes in saliva: SIgA and IgG. caries. did not find that salivary antibodies in man play a role in 8. Since innate and adaptive immune defenses may influ- several epidemiologic investigations have uncov. J. They tooth surface.6 Summary protection against caries [106]. links between immune deficiencies associated with malnutri- endodontic inflammation and cardiovascular out. and inhibit the adher- population-based study of Swedish women [99]. check the purported association between salivary . In the researchers from MAR Dental College carried out future. In 1978. a protective role for salivary observed a greater CHD incidence among men with sIgA was postulated [103–105]. individuals with low caries susceptibility exhibited tions have uncovered relationships between den. mouth which is produced by gland-associated odontically treated teeth and CHD nor between immunocytes. different studies got contrary results and conclusions. ies susceptibility [107]. and (2) elevated occurs because of imbalance in the homeostasis systemic cytokine levels have been observed in con. The former tors for the development of CHD. Salivary junction with both disease processes [97]. However. Challacombe S. those hypothesized for associations between peri- odontal disease and CHD. found that caries-free subjects or As stated above. other studies have not ribosomal preparation than subjects with high car- found significant relationships. factors that affect salivary flow and saliva compo- ing endodontic disease to CHD might be similar to sition [102]. teeth with periapical disease and CHD from their modulate enzyme activity. Mechanisms link. So dental infections. especially long- endodontic origins.

Further studies should be carried out to what factors bring about these differences that find the truth.3 patients with RA and 102 non-RA. filled teeth (DMFT) index was used mothers [110]. Caries indices included T-lymphocytes resulting from HIV infection DMFS and DFS (coronal caries) and DFSrc (root might alter salivary flow rate and impair the caries). systemic inflam. such as the study designs. positive children from 0 to 14 years infected by missing teeth. et al. informa- to classify caries. Ling and H. Those changes increasing age and lower average stimulated sali. In 2004. including cant except for an overall increased DFSrc increased prevalence of dental caries. while the inci- study to determine if there was an association dence of permanent tooth dental caries is less between HIV infection and dental caries among than that of a group of noninfected household women enrolled in the Women’s Interagency HIV peers [115]. They found Phelan J. However. However. In order to exclude the common environmental factor.0002) compared to seropositive which can lead to substantial loss of functioning women without AIDS [109]. but principally attacks flexible (synovial) (P = 0. and mobility if not adequately treated. It can be a disabling and painful condition. Subjects included 538 HIV+ and 141 It has been hypothesized that immunodefi- HIV− women at baseline and 242 HIV+ and 66 ciency and a progressive decrease in CD4+ HIV− women at year 5. DMFS increased with increase in the oral cavity [116]. also reported that seropositive RA. thus contributing to data revealed a 1. The results showed that there were no statisti. and decayed and/or filled (DF) root joints. And reasons are still unknown.142 Z. prior to 1992. surfaces (P = 0. both the primary and secondary dentition among globally. since all the studies had their limi. Between 1992 and 1996. Rheumatoid arthritis (RA) is an autoimmune women who fit the Center for Disease Control disease that results in a chronic. could be contributing factors for the development vary volume. their HIV-negative household peers.9 million] people a group of HIV-infected children as compared to were living with HIV at the end of 2011. A recent associated with smoking [108]. The decay. published a paper in Journal of that HIV-infected children have a high prevalence Dental Research titled “Dental caries in HIV.” The authors conducted the prevalence in permanent teeth. These studies showed that there extent of caries [104]. ing early childhood caries (ECC)) in the primary tations. 34. Root caries results were not signifi.2-fold-higher caries prevalence increased bacterial colonization in the oral cavity among HIV+ women compared with HIV− implying that cariogenic bacteria may also women. DMF surfaces organs. there kit.5.0 million [31. Cross-sectional analysis of coronal caries secretory immune system. study by Liu and coworkers examined the effect .003). of dental caries in the primary teeth and a low seropositive women. if the sample dentition of HIV-infected children as compared size was insufficient or not. Longitudinally. At the same year. (CDC) AIDS criteria were also more likely to matory disorder that may affect many tissues and have more DMF teeth (P = 0. exist in dental caries between HIV-infected chil- dren and a noninfected control group. of HIV-associated oral diseases.2 HIV and Dental Caries Tofsky et al. healthy case million human immunodeficiency virus (HIV)- controls were taken part in the study. Whole unstimulated saliva was tion about dental caries in HIV-infected children collected to assay sIgA using a commercial ELISA was very limited. Forty-eight It is estimated worldwide that there are 2. compared the baseline prevalence and 2-year incidence of dental caries found in According to the World Health Organization.4–35. it has also influence biomarkers and antibodies in oral not always been clear from past studies exactly secretions. dental caries in the primary teeth of HIV-infected RA subjects with respect to salivary sIgA and the children [111]. were three published cross-sectional studies of cally significant differences between RA and non. It’s hard to explain all the was a higher prevalence of dental caries (includ- contrary results. or technical variables to healthy children [112–114]. A. Study. Tao sIgA and dental caries with special reference to Mulligan R. 8. et al.004).

blood pressure or diabetes and those with a blood missing. mutans colonization. Peterson and Several studies have demonstrated higher his colleagues got data to support the hypothesis rates of oral pathology in dialysis patients with that the relative paucity of caries in patients with one or more oral symptoms such as xerostomia. and the status of immuno. complications that arise from the disease and its and a state of reduced immune function that may treatment. loss of taste. And they also inappropriate dietary intake (such as ingesting revealed decreased salivary flow rate in the HIV+ too little protein and too much calorie-rich. loss of attachment. The increased periodontitis and dental caries including S. tis and other oral and dental conditions [120]. different researches got Often. high- group [117]. which has been associated with meta- bolic changes. ease [121. is a progressive loss in rate and composition. such as those with high uremic patients have higher rates of decayed. They found hypoplasia. dental caries and CKD. perhaps as a consequence of a The symptoms of worsening kidney function are high salivary urea and phosphate levels. count. Some researchers reported that the prevalence of sent an important. Chronic periapical and mucosal lesions than the general kidney disease may also be identified when it population. but not with viral load or CD4+ counts. advanced age. Some studies showed that of kidney problems. fat food) as compared with dentated persons. 122]. Increased dental calculus renal function over a period of months or years.6 Dental Caries and Kidney to have a “bad” or a “metallic” taste in their Diseases mouths. problem dental caries was low in children with renal dis- [118. On the other hand. and infec- which is clearly suggesting that other HIV. tongue coating. chronic kidney disease is diagnosed as a different results. or enamel acteristics of S. concurrent medications. Poor oral health in CKD patients may thus repre. but often overlooked. We know that xerostomia (or dryness that HIV+ individuals experienced significantly of the mouth) may predispose to caries and gingi- higher levels of S. Studies in the general population suggest associated factors mechanistically mediate S. tions. masticatory function. oral ulceration. approximately 30 % of patients with advanced CKD are reported 8. sore mouth.8 Dental Caries and Systemic Diseases 143 of HIV infection on the level and genotypic char. mutans. denced in HIV+ individuals from this study and Whereas the number of teeth is of importance for others. common existing additional dis- In addition to the systemic manifestations and eases such as diabetes. 119]. has been observed. dysphagia. or pericarditis. such may be more severe in CKD patients because of as cardiovascular disease. mutans. plaque by metabolic end products of urea . additional studies are required to eluci. and filled teeth. and changes in both salivary flow chronic renal disease. diverse drugs. tus. mastication. and sometimes the conclusions result of screening of people known to be at risk were contradictory. nonspecific and might include feeling generally When it comes to the relationship between unwell and experiencing a reduced appetite. The consequences of poor oral health leads to one of its recognized complications. rates of CKD patients lead to tooth loss. changes in the mouth are common in increase the risk for consequences of periodonti- patients with chronic kidney disease (CKD). mutans significantly correlated with CD8+ ties with speech. that edentulous subjects are prone to have an mutans colonization in saliva. denture retention. Interestingly. inadequate occlusive surfaces or the limitations of prostheses. Since more dental caries was evi. chronic renal failure results from alteration of taste disturbances. mucosal inflammation. As early as 1985. anemia. having premolar and molar date and understand the correlation between the teeth is especially important for nutritional sta- colonization of other cariogenic microbes. and relative with chronic kidney disease. also known as of taste buds. a reduced number Chronic kidney disease (CKD). uremic odor. which suppression at the advanced stages of HIV may result in chewing difficulties because of infection. the level val inflammation as well as contribute to difficul- of S.

chewing pain and tooth loss. (CKD) compared to healthy individuals.7 Dental Caries GERD are not usually noticed until they cause and Gastrointestinal significant damage. The data further suggested that habits. Moreover. The oral lesions resulting from 8. dental caries and gastrointestinal diseases is from dental caries is still our focus in this chapter. These changes may be permanent or temporary. especially the neu- tralization of end products of bacterial plaque Gastroesophageal reflux disease (GERD) is a due to the increased pH resulting from urea chronic symptom of mucosal damage caused by hydrolysis in the saliva. six articles met the inclusion There are also some interesting researches criteria. evi- and adolescents with chronic kidney disease dence suggests that nutritional deficiencies. and abstracts of impaired immune responses [5]. the edentulous patient without den- mal may be at increased risk of caries. the eating Some studies on the oral health of patients with of some foods will cause pain. tooth sensitivity. the lower esophageal sphincter. 125]. So the authors concluded stomach acid coming up from the stomach into that data in the literature weakly support a lower the esophagus [127]. mean caries indices in both primary (dmf) and permanent (DMF) teeth were lower in the chil- dren and adolescents with CKD compared with 8. chronic reflux reported an inverse relation ache and infection alter eating and sleeping between caries and gastroesophageal reflux and . expulsion of gastric reflux from the esophagus. why the denture wearer does not achieve the nec- A recent systematic review published in essary breakdown of food substances. A subsequent and the effect of S. that connected dental caries and gastrointestinal ies which showed susceptibility to bias and pos. person with a deficient masticatory performance. impaired port of this conclusion. In addition. diseases. are associated with the evaluation of title. or a hiatal hernia. including abnormal relaxation of [126]. carious teeth become pulpitic. Others have not found any evi. In these patients. transplanted patients whose renal function is nor. The Pediatric Nephrology tried to determine whether research indicated that the chewing efficiency of there is any evidence in the literature referring to those wearing dentures was about one-sixth that a lower prevalence of dental caries in children of a person with natural teeth. before. dence that the prevalence of dental caries in per. In the edentulous is poor [123]. After regardless of their cause. the low and Gastroesophageal Reflux prevalence of dental caries may be associated Disease with salivary characteristics. keywords. Tao metabolism. As we mentioned However. Ling and H. the most significant relationship between dimension of occlusion to irreversible damage. and metabolic processes.144 Z. which normally ies that provide better scientific evidence in sup. especially tures is the most vulnerable to gastrointestinal if enamel hypoplasia is present and oral hygiene and other related problems.7. therefore tooth. Despite the pruritus and Diseases burning on the oral mucosa. the articles selected. One study provided a sound basis for [124. GERD is usually caused by prevalence of caries in children and adolescents changes in the barrier between the stomach and with CKD than in their healthy counterparts the esophagus. There is still a lack of well-designed stud. dietary intake. and decrease in the vertical To date. sour taste. reduced consumption of fiber-rich foods that are manent teeth is significantly different in CKD hard to chew could provoke gastrointestinal dis- children when compared with healthy children turbances. Three of these six articles included stud. such as gastroesophageal reflux disease sible confounding factors. the results have been contradictory.1 Dental Caries healthy individuals. holds the top of the stomach closed. mutans on the ulcerative assessment of the six studies revealed that the colitis. aphthae.

Although there were more subjects with next year. of the insulin-producing beta cells of the islets of gest that indigenous gut microbiota play a key Langerhans in the pancreas. and sample size. in 2011. and “other specific types. have abnormalities of the immune system.0 billion USD in . estimated that the ability to bind the collagen and resistance to direct medical costs of T2DM and its complica- phagocytosis [87]. they published another paper Streptococcus mutans in the GERD group com. tests. to show that infection of specific strains of pared to the control group (42 % vs 25 %). of gradual onset. induced bacteremia. So the controls. In contrast. Based on protein (CBP) caused hemorrhagic damages in case numbers in 2007 and projected case num- the murine brain and other tissues because of the bers in 2030. 133]. oral clinical examination. disease that causes 2030 [135]. regulation of mucosal immune ized by insulin resistance. Linnett et al.2 strains of S. It’s no doubt that diabetes mellitus is a rapidly growing health concern in both developed and developing nations. The differences among the different studies may 8. Future studies are needed to explore the truth.” whether these problems are a cause or a result of Type 1 diabetes mellitus is characterized by loss the disease is still unclear. CBP-positive and phagocytosis-resistant strains On the other hand. only a tions were estimated to be 26. Diabetes mellitus is classi- unknown though theories exist. conducted for 52 from UC patients.4 million (9. in 2012. for aggravation of UC caused by S. They stated that it’s the first Silva et al. leading to insulin role in the pathogenesis of inflammatory bowel deficiency. the detection teria (lactobacilli and streptococci) observed in frequency of specific strains of S. inflammation of UC. Type 2 diabetes mellitus is character- disease. mutans. large intestine. mutans- They attributed this to the low prevalence of bac. The Center for Disease Control inflammation and sores in the inner lining of the (CDC) estimates that in the United States alone.8 Dental Caries and Diabetes be explained by the different research design.8 Dental Caries and Systemic Diseases 145 showed a small number of caries in individuals limited number of strains are possible risk factors with GERD as compared to control groups [128]. the Mellitus patients from different areas. was extremely higher than in children (31 boys and 21 girls) with a definitive non-UC control subjects. mutans may ence was higher in GERD patients compared to be involved in the pathogenesis of UC. suffer from DM. [23] did not find relationship between paper describing the involvement of oral bacteria GERD and changes in the oral cavity by saliva in UC pathology [134]. et al. People with UC fied into four broad categories: type 1. Nakano et al. According to the World 8. Thus the authors specu- history of GERD. type 2 diabetes mellitus affects almost In 2011. intestinal microbiota in a genetically susceptible Type 2 diabetes is the most common type. mutans is one of the risk factors in aggravating difference was not statistically significant [130]. which may be com- response to unidentified components of normal bined with relatively reduced insulin secretion. with projections that Ulcerative colitis (Colitis ulcerosa. such as the saliva of patients with chronic reflux [129]. China. Current theories sug. lated that such specific strains of S. or histopatho- logic examination of the palatal mucosa [131].2 S. In host is at the core of these diseases [132. In normal situations. type 2. The cause of UC is undiagnosed [136]. They found that caries experi. and 148. mutans and Ulcerative Health Organization (WHO). 25. found the specific 92. approxi- Colitis mately 364 million people globally suffer from diabetes mellitus (DM). UC) is a DM-related deaths will double from 2005 to chronic. Wang W. or 8. with 7 million currently blood.7 %) Chinese adults. Moreover.8 million Americans. The main symptom of active dis. the S.7.3 % of the popula- ease is usually constant diarrhea mixed with tion. or long-lasting. mutans that express collagen-binding million adults are in the prediabetes. but gestational diabetes.

In with and without diabetes. betes and dental caries has been investigated Other researchers. physiologic. and medical variables asso- In 2004. The authors found between diabetes and oral health. the diabetic group showed a higher periodontal disease [139. and the existence of compli- developing new and recurrent dental caries [141].1 Epidemiological Studies root caries in an adult type 1 diabetic population of Diabetes and Dental Caries and evaluate demographic. Diabetics were tes and risk for coronal or root caries exists [143]. years of age. Likewise. In 2008. Later. reported that patients with diabetes are suscepti. matched nondiabetic controls. 140].and gender- determine whether a relationship between diabe. Patiño bolic control exhibited higher glucose levels in et al. the prevalence and dental caries. cations of the disease exerted an influence upon However. This review suggests 2006. no clear association has significant difference or even a decrease in caries been clarified till now [142]. Ling and H. and a group of non-diabetic controls It is widely understood that diabetes patients matched for age and sex. significantly higher DFS rates as compared with and tooth loss. which could increase their risk of duration of diabetes. However. dietary. specifically that adult type 1 diabetic subjects did not have focusing on periodontal disease. categorized into well-to-moderately controlled Here are two studies that reported a greater and poorly controlled groups. previous caries experience. carried out a cross-sectional study involving resting saliva and a significantly higher caries 175 subjects to determine the frequency of caries. incidence compared to those with good meta- periodontal disease. have detected no since the last century. the metabolic control of the disease. A decade ago. It reports increased. a study evaluated the caries incidence in vary flow rates and buffer effect. and more fre- 64 children and adolescents (8–15 years of age) quent growth of yeasts than their nondiabetic . conducted the other work which not make a distinction between type 1 and type 2 comprised 90 type 1 diabetics between 18 and 50 diabetes mellitus in this chapter.8. poor types among the study variables [138].2 billion USD with type 1 diabetes mellitus over a 3-year period in 2030. from the onset of the disease in relation to meta- sumes a large portion of healthcare expenditures bolic control and to caries-associated risk factors. of RDFS was higher in the diabetic subjects as and similar caries experiences between those compared to recruited control subjects [146]. and tooth loss in patients bolic control. Moore et al. xerostomia. another study in Lithuania comprised 68 that currently there is insufficient evidence to 10–15-year-old diabetics and 68 age. decreased. The most influential determinants affected by diabetes mellitus types 1 and 2. The results indicated that T2DM con. high levels of salivary lactobacilli [144]. reviewed the post-1960 ciated with decayed and filled surfaces in the English-language literature on the relationship crown (DFS) or root (RDFS). Since we oral hygiene. group. and will continue to place a heavy burden on Results showed that patients with less good meta- health budgets in the future [137]. Tao 2007 and were projected to be 47. periodontal. Studies have incidence of caries than the control group. lower sali- In 2002. Taylor et al. however. The literature does not describe a their control subjects or published age-adjusted consistent relationship between type 2 diabetes NHANES III findings. on specifically analyzing the diabetic ble to oral sensory. and salivary dis. published a paper to describe the prevalence of coronal and 8. tes mellitus and dental caries prevalence. behavioral. the development of dental caries [145]. Their results showed are at an increased risk for oral complications that under similar conditions of oral hygiene and such as candidiasis. dental caries. susceptibility between diabetic and nondiabetic patients. Their for high caries development during the 3-year results showed a difference between the two follow-up period were metabolic control. the orders. salivary. erosion. although the relationship between dia. and salivary flow. and care about the overall association between diabe. diabetics had fewer caries and plaque. we did Miralles et al.146 Z. They found that history of dental caries in people with diabetes.

or yeast growth during fol. In spite of the dif- cose were analyzed. received intravenous injections of alloxan mono- ies experience in this study population could be hydrate [150]. caries. Thus. and glu. prevalence of severe untreated caries. Hartles and Lawton related to plaque accumulation and/or to changes reported that the mean number of carious teeth in saliva induced by diabetes mellitus [147]. A total of 63 (10–15 years old) either directly or indirectly [151]. 1957. Beck et al.and sex-matched nondiabetic con. similar in diabetics and their controls. but the level of metabolic con. which is different to those challenges pre- and prevalence of severe dental caries in adults?” sented by the former [153]. the same authors published another cantly higher for the injected animals than for the paper to analyze possible associations between controls. Two per rat and the mean caries score were signifi- years later. yeasts. total As stated above. mutans streptococci and yeasts than poorly con. further studies of cose concentrations were higher in diabetics than the potential association between diabetes melli- in controls throughout the 2-year period. However. results of these studies have IgA and IgG. lactobacilli. oral hygiene. carious molars and carious legions. dental caries can be sis for Master degree. protein. In 2009. trols. whereas salivary IgA. causing an alteration in the salivary secretions. firmed that diabetic conditions enhance dental Salivary flow rates. and noncon- mutans streptococci. buffer effect. found that Data of 701 subjects with diabetes and 3. normal rats vary flow rate but were not associated with the did not differ from caries-susceptible rats that level of metabolic control of diabetes. there trolled diabetics. in addition to dental plaque as a common caries risk factor. and there will be increasing numbers of older patients prevalence of at least one root surface with caries at risk of root-surface caries. Their tus and dental caries are suggested. diabetes- induced changes in salivary glucose and albumin 8. ventional cutoffs to classify good and poor low-up. diabetes control [149]. some studies trol of diabetes had no influence on salivary flow reported that diabetes enhanced the incidence of rates and buffer effect. Means of 2-year decayed/ ference between diabetes mellitus types 1 and 2. They also found that peo- and Nutrition Examination Survey (NHANES) ple who experience both types of caries had more conducted from 2003 to 2004 were used. the absence of stan- ences were observed in the counts of lactobacilli. Findings gingival recession at baseline [154].8. and glu. results also suggested that.636 sub. coronal and root caries do tend to appear together jects without diabetes from the National Health in the same individuals. High caries levels in dia. concentrations caries in WBN/KobSlc rats [152]. are also contradictory reports. dard criteria for caries evaluation. No differ. “Is latter poses a complex challenge for dental practi- there an association between diabetes mellitus tioners. As world’s of her study suggested that prevalence of severe population ages and retention of teeth increases. such as small sample size.2 Root Caries and Diabetes concentrations are indicative of caries develop- ment among diabetics [148]. The that aimed to answer the research question. protein. dental caries whereas another did not. According to its location. amylase. In experimental diabetic rodent animals. albumin. Abay conducted a study divided into coronal caries and root caries. Root caries has a . Well-to-moderately controlled diabetics or filling did not differ between adults with and had fewer decayed surfaces and lower counts of without diabetes [149]. over 2 years. in her the. As early as betics were significantly associated with age. probable way in which the injection of alloxan nants in children with type 1 diabetes mellitus can influence the incidence of dental caries is by and their age. and decreased unstimulated sali. High car. of mutans streptococci. Nichols and Shaw reported that in terms of plaque score.8 Dental Caries and Systemic Diseases 147 controls. shown conflicting conclusions. and salivary factors. And the authors proposed that the most caries increments and selected caries determi. A recent study diabetic and nondiabetic pairs were examined for published by some Japanese authors also con- dental caries. missing/filled surface (DMFS) increments were the reasons may be methodological difficulties.

. phos. root caries [157. Recently. HbA1c. the change of microbiology determine the effect of type 2 diabetes mellitus in the oral cavity of diabetes patients may also have on coronal and root-surface caries. Subjects of relationship with root caries. the use of pared with nondiabetic subjects had a higher culture-independent methods has played a key role prevalence of root-surface caries and a higher in the discovery of previously unrecognized species number of decayed/filled root surfaces. Root-surface caries was associated with an about the effect of salivary factors like salivary increased count of mutans streptococci. Since oral microbiota plays an important role in sectional study was conducted in Thailand to the root caries process. another stratified cross. and fluoride in diabetes mellitus. val crevicular glucose levels in people with betic subjects as compared to recruited control poorly controlled diabetes [155]. phosphate. supragingival plaque samples [164]. periodontal disease and Although no significantly higher DFS (decayed associated attachment loss and gingival recession and filled surfaces in the crown) rates were may mediate increased root caries.148 Z. compounded noticed. and Streptococcus interme- saliva is responsible for establishing protective dius in their supragingival plaque than nondiabetic environment against dental caries.’s study suggested that betic subjects with dental caries were included as diabetes and poor glycemic control may not be . we will talk subjects. firstly. flow rate and adequate level of calcium. result of chronic hyperglycemia [159. lactobacilli. ies in an adult type 1 diabetic population in 2001.and sex-matched nondia. evaluated the possible protective role of salivary factors in diabetes mellitus type 2 patients with dental caries. FMA5. a total 8. The tal disease and subsequent loss of attachment. Many of these individuals may indices were found to be significantly high. insufficient betic patients as compared to controls [159]. neuropathy affecting the salivary glands as a described the prevalence of coronal and root car. the prevalence of RDFS (decayed and by reductions in salivary flow and elevated gingi- filled surfaces in the root) was higher in the dia. Root caries was 105 type 2 diabetic patients and 103 nondiabetic thought to be associated with Streptococcus mutans.8. in diabetes. Except for these three bacterial species To analyze the possible factors connected the we just mentioned.. evidence exists to support or refute an association Salivary flow is known to be reduced in long- between diabetes and root caries [155]. we have to talk about Atopobium spp. Jawed et al. jects had higher levels of Treponema denticola. assumed. Pseudoramibacter periodontal diseases. Moore et al. Their Lactobacillus (spp. Diabetes has been alactolyticus.). considering that Streptococcus oralis. Therefore. Streptococcus sanguinis. and Actinomyces (spp. Ling and H. and Propionibacterium sp. Currently. Secondly. Olsenella spp. while be more likely to have chronic systemic disease. and DMFT other age group. were also commonly found [163]. on the culture method [161. gingival recession will cause the expos. strain found to be bidirectionally linked with periodon. caries was far more complex than previously and existing coronal caries [156]. As study showed that significantly more diabetic sub- a result.) based results found that type 2 diabetic patients com. The blood glucose. In 2007. ing of tooth’s root and contributing to the risk of Prevotella nigrescens. more missing teeth. And the authors with root-surface caries included type 2 DM. 158]. The in the oral cavity as well as in redefining the patho- authors also found that the factors associated genesis of the major oral infections. and So we discuss the relationship between root caries fluoride were found to be significantly low in dia- and diabetes separately. a found that the microbial flora associated with root low saliva buffer capacity.3 Tooth Loss and Diabetes of 398 diabetes mellitus type 2 patients with den- tal caries and 395 age. the salivary flow rate. and yeasts in saliva and of Streptococcus mutans in phate. additional species. subjects [146]. The results of Lin et al. In their study. 160]. So far. at the same age and gender were included. This is thought to be due to As we mentioned before. such as root caries and diabetes. standing diabetes. 162]. Tao higher prevalence among older adults than any controls. calcium.

sex. hospitalized because of significant associations of tooth loss with HbA1c pneumonia. bronchioles. It is well known [169]. but the most common route of infection is them are the aspiration of oral pathogens into the aspiration of what pneumologists have long lungs. Thus it’s not surpris. the oral of tooth loss [166]. the pathogen is particularly viru. matched to tions of periodontal disease with HbA1c. compared with two groups of patients among the middle-aged men may reflect associa. Among tion. An infection occurs when the host’s defenses are Pascual-Ramos et al. a recent study found that actinomycetemcomitans. ies as control group. in healthy patients. disease were enrolled in the study and divided into ing that many of the diseases that occur in the two groups: 100 children with dental caries as oral cavity could be also found in the upper air. Dental caries was mechanical defense mechanisms. mote adhesion and colonization by respiratory isms might infect the respiratory tract [166]. from infected lungs. pathogenesis of respiratory infections. and tion (URTI) rates. with poor oral hygiene and dental caries [170]. In are lots of anaerobes implicated in the destruction 2011. it’s not easy for an infec. Pascual- HbA1c among men aged 40–64 years but not Ramos et al. The explain the potential role of oral bacteria in the microorganisms may enter the lung by inhala. patient group and another 100 children without car- way regions. In addition. Actinobacillus betes [165]. Since diabetes is third-grade caries and pneumonia in 30 consecu- a major risk factor for periodontal disease. teeth index. a Korean study has identified a relationship of periodontal tissues that have also been isolated between total tooth loss from any cause and dia. The latter is so scored according to decayed. there active caries lesions and missing teeth [142]. made a summary of the dif- compromised. coronal and root-surface caries experience in Since community-acquired pneumonia and lung older adults. early childhood caries during subsequent years voir of respiratory pathogens. And their results showed that the URTI way and lung parenchyma are sterile. pathogens. with SLE. Fusobacterium nuclea- having 19 or fewer teeth was associated with high tum. although they had no information on the causes Compared with ambulatory controls. It usage in both groups since birth were identified must defeat sophisticated immunological and according to the medical records. from that the respiratory system includes the nasal and Turkey showed the possible association between oral cavity: the sinuses and larynx as the upper poor oral hygiene and upper respiratory tract infec- airway and the trachea. URTI rates and antibiotic tive agent to reach the lower respiratory tract. and hospitalization date. cases by age. periodontal disease-associated enzymes that pro- Therefore. Children without any systemic alveoli as the lower airway. it is plausible that oral microorgan. the tive women with SLE. but there is a tendency for more abscesses may be due to anaerobic bacteria. found a strong association between among those aged 65–79 years.8 Dental Caries and Systemic Diseases 149 associated with an increased prevalence of past obstructive pulmonary disease (COPD) [167]. despite the rates were significantly higher among children heavy bacterial load found in the upper airway. A research conducted by Eldem et al.9 Dental Caries number of caries per patient [168]. the destruction of salivary pellicles by Dental plaque and poor oral health have been periodontal disease-associated enzymes that mod- associated with nosocomial pneumonia and chronic ify clearance of pathogenic bacteria from the . There is also and Respiratory Infections evidence that the occurrence of respiratory tract infections during the first year of life is associated The anatomical continuity between the lungs and with a significantly increased risk for developing the oral cavity makes the latter a potential reser. health of patients with pneumonia was worse as reflected by a higher frequency of periapical lesions and cervical and third-grade caries and a higher 8. and Pseudomonas aeruginosa. the distal air. hospitalized and ambulatory. or the inoculum is overwhelming. bronchi. and filled efficient that. However. ferent mechanisms that have been proposed to lent. for example. missing. the modification of mucosal surfaces by referred to as oropharyngeal secretions.

Benjamin RM. Holmstrup P. Iran. Clin. 982–6. pathogens [168. Ratanasiri A. 2009. Plaque and systemic disease: a reappraisal of 24. Kolltveit KM.33:401–7. Diseases of the arteries. Dreizen S. Tata 3. Reasons for extraction of on Oral Health. 18. Yee M. allel sequencing. Enough to make you sick: 82–4. Han YW.61:85–92. Debelian GJ. Seyednejad F. editor. Matse JH. 4th Forman D. 2013. 2007. Hall G. In: Osler W. Vitiello PF. complications of cancer radiotherapy. Tronstad L. Savadi Human Services. Periodontal disease as a risk factor for Australia’s Health. Ferlay J. 9. et al.19:3032–8. TW. 10.95:s1–6. Brown LR. Clin Microbiol 29. Laboratory Science: theory and practice. Kilian M. et al.125:158–9. Vissink A. J Clin 6. Clin Microbiol Rev. Roper JM. Tronstad L. 22. WR. Med Prin Pract. Clin Microbiol Academy. Minimizing oral complications of cancer 13.92:485–91. Philadelphia: Lea and Febiger. Jenkins WMM. Oskoee S. Kay EJ. 2013. Drane JB. scaling in individuals with periodontal inflamma- 7. Chambers MS.28:2205–9.13:547–58. Löe H. how income and environment affect health. Clin 21. Oral health: the silent epidemic. Staversky RJ. M-M SA. McGraw-Hill Education. tooth brushing and 1984. 2000. What every health professional needs and quantitation by lysis-filtration of bacteremia to know. Oral Health Care – Australia’s National Oral Health Thailand. Olsen I. 2009. Postgrad Med. severity. 2000. Abraham-Inpijn L. 2003. Discovery Tehran. Osler W.22:239–44. Oral Rev. Crit 11. Jaidee J. and alteration of the respiratory 16. contributions by Americans and foreign authors. Oliver RC. get for hyperoxia-mediated impairment of postnatal .13:547–+. Tao mucosal surface. in extra-oral infections and inflammation. General. 5. 1995. Oral health in America: a report of the Surgeon 863–6. 2012. Mohammadi N.com. Li X. 2000. Factors related to tooth loss due to den- tal caries among workers in an industrial estates in 1. Kolltveit KM. permanent teeth in general dental practices in 2. Dental caries. Rockville: Department of Health and 31. 28.15:976. Ling and H. Modern medicine: its theory and practice in original 27.150 Z. extent.9:851–8. 2013. 1989. 622. 2011. CA Cancer J ed. Mobile microbiome: oral bacteria 1977. 171]. 1994. 17. Ochei. Thoden van Velzen SK. 978–82. p. Burlage FR.S. The human sali. J Dent. 2012. Jansma J. Lemon JC. Prevention and treatment of the therapy: an overview.2: 15. 2012. Melbourne: National Health Strategy. Wang X. Hedberg M. 1991. J Med Assoc Thai. Forner L. discussion 858. Li XJ. Klock KS. after different oral surgical procedures. Anaerobic bactere. 1908. Canberra.19:336–41. 2010. Parahitiyawa NB. Bray F. teremia: beyond endocarditis (vol 22. Center MM. Wright Paper No. 2009).61(2):69–90. Gothenburg. J Clin Periodontol. 12.14:213–25. 2001. periodontal disease and different systemic 25. Fadel HT. J Periodontol. apy. Microbiology of odontogenic bac- 4. of bacteremia after chewing.369:51–9. C. Spielmann N. Chatrchaiwiwatana S. Community Dent Oral odontal tissues to promote infection by respiratory Epidemiol.11:209–20. J Clin Periodontol. Ward E. Oskoee PA. Pitts NB. Brown LJ. Olsen I. The relationship of oral to overall health 23. Systemic Rev Oral Biol Med. Australian Institute of Health and Welfare. Type II epithelial cells are critical tar- 1992. Heimdahl A. Research 32. Wang XY. Department of Health and Human Services. 2008. Etebarian A. Martin JW. The reasons for the extraction of various tooth types in Scotland: a 15-year follow up. Spijkervet FK. Rev. Ebrahimi Chaharom ME. vary RNA transcriptome revealed by massively par. Jemal A. Yam WC. benign and malignant parotid gland tumors. Evaluation of 14. Ilsley D. Selwitz RH. Periodontal diseases in radiation-induced class V dental caries in patients the US in 1981: prevalence.22:386. Loesche WJ. Clin Chem. and role with head and neck cancers undergoing radiother- in tooth morality. and prevalidation of salivary extracellular microRNA 20. Larsen T. Toth BB. heart disease. Fleming TJ.29:401–7. Moorer Microbiol. Gu J. con-sequences of head and neck radiotherapy.60:363–70. Leung WK. Incidence the focal infection concept. Daly TE. Public Health Rep. pg 46. Studies on the associations between dental tion. In: Medical Cancer Res. Haugejorden O. National Health Strategy. Pus abscess and wound drain. Compendium. McGuire T. Jafarian M. 1998. RP. J Dent Res Dent Clin Dent Prospects. U. Olsen I. Detection and longevity. mia and fungemia in patients undergoing endodontic Coppes RP. Samaranayake LP. 26. tuberose. McCaul LK. 2006. Systemic conditions. treatment. diseases caused by oral infection. caries. 1990. References Soontorn S. Res. Plan 2004–2013. Tronstad L. Global cancer statistics. National Health Advisory Committee 19. et al. Yoshizawa J. Ismail AI.3:281–7. Primary reasons for extraction of permanent teeth in Norway: changes epithelium by cytokines originating from peri- from 1968 to 1988. Ann Periodontol. biomarkers panel for the noninvasive detection of Lancet.58:1314–21. J Dent 30. 1. 2004. 8. Jin LJ. Oncology. Doctoral theses from Sahlgrenska diseases caused by oral infection.

report 2003: continuous improvement of oral health 2009.9:15. J Clin Pediatr Dent. Dental 61. 40. The influence of dental caries on body growth in .9:550–8. Trovik TA. 2013. A population-based case–control 2010. 54. Relationship between high weight Causes Control. Kay EJ. 41. Health. Wactawski-Wende J. Muto M. Hodgson BD. Willerhausen B. Otolaryngol Head Neck Surg. 2000.88:342–50. Lodolini G. Multi. Bladstrom A. 2013. Acta Otolaryngol. Dental caries and children’s weight. JAMA BMC Oral Health. Oral Oncol. Kawase T. Mendez DB. Furlong R. Dental caries and head and neck cancers. Impact of poor oral health on children’s school 36. Ahmed Cancer. Geneva S. Munshi AK. Reifsnider EMC. Shimada H. Ness A. Yusof N. Vaughan-Williams E. Oral Health Programme. Soc Sci Med. Mishu MP. Cancer Hohenfellner K.26:38–42. Eur J Med Res. Periodontal disease. mous cell carcinoma. Duncan K. Featherstone JD. Dounis G. 2004. MF. Kaminsky S. 49. sequent growth on the development of dental caries 44. Masood M.17:1222–7. 2013. Northstone K. and risk of head and neck cancer: a meta-analysis. Public Health Rep. Khosla T. Kamiyama K. 14:164. in the 21st century: the approach of the WHO Global 59. 2008. 235–42. Kaihovaara P. Miller J. Wright CM. Epidemiol. Hobdell M. the Sudan. of nursing caries on body weight in a pediatric popu- Acetaldehyde production from ethanol by oral strep. children in Sendai. Schildt EB. health and risk of squamous cell carcinoma of the 55. and caries frequency in German elementary school 38. Kay EJ. comparison of caries time trends in nursery school centric case–control studies. van Amerongen EW. 39. A systematic review of dental disease in BMC Public Health. 2010. Sasaki H. Tajima attendance and performance. Tezal M. Khan MH. Cancer Epidemiol Biomarkers Prev. 2009. Jaafar N.37: cations for carcinogenesis in upper aerodigestive tract. Communit Dent Oral 2007.38:408–14. Lancet Oncol. Ontario Dental Association. 2013.166:1159–73.9:400–4. 2013. JY. and early childhood caries in a WIC population. et al. Meyer M.291:L1101–11. Gu WJ.23:334–9. Department of Health and Human Services. 45. Tooth loss Toronto: Ontario Dental Association. 1980.139:1054–60. tooth loss. Pan Afr Med J. Liu Y. Hu Z.71:1644–52. Mobley C. Int J Dent. Ditmyer M. Hubbard RM. 2008. 5 p. Relationship between untreated dental case–control study of determinants for high and low caries and weight and height of 6. Japan.10:24.8 Dental Caries and Systemic Diseases 151 lung development. Giovannucci E. Hassan MI.21:567–75. Mahachi L. A Sabbah W. Salaspuro V. Oral 2:853. Stamperdahl J. Lee 125:1327–36. Am J Public Health.8. 2010. Is there a relationship between birth weight and sub- 125:158–9. Joshipura K. Crean SJ. The world oral health growth and dental caries.12:989. 57. Support Care 48. Den Besten PK. and 53. 2000. Scannapieco FA. Childhood 43. Saito T.2013:629675. 46. Napeñas JJ. Wennerberg J. Jackson SL. tive cohort study. 2010. Matsuo K. risk for head and neck squamous cell carcinoma: the 52. Oral infections and some lifestyle childhood dental caries: the convergent roles of factors as risk factors for oral and oropharyngeal squa. et al. 51. in Japanese. lation. Oral health status of 12-year-old school children 34.14:302–5. Ohtsu A. Physiol.18:1007–21. Teeth loss and risk of cancer at 14 common sites 2011. Jiang Y. Divaris K. Acetaldehyde production by non. K. Mafuvadze BT. Kashiwase 56. Kurkivuori J. Ali RW. Wennink JM. United States Public Health Service. 58. and body mass index. Y. Cisneros GJ. 1995. Benjamin RM. children. Kotch JB.10:24–31. et al. Wei B. Vann Jr WF. Krummenauer F.to 12-year-old pri- dental caries prevalence in Nevada youth. Zhan L. Hitomi Y. Am J Epidemiol. Mafuvadze B. Int J Cancer. Ramakrishna Y. Wunsch Filho V. Adler NE. 35. (ISOO). 33. study in southern Sweden. Relationship between severe early childhood caries pathogenic Neisseria in human oral microflora: impli. in Khartoum state. 2005. Suzuki T. Nurelhuda NM. stress. Hong CHL. Haas G. Boffetta P. Ten Cate JM. bacteria and disadvantage. Pahel BT. Oral health and J Multicultural Nurs Health. MalekMohammadi T. tococci.43:181–6. Rockville: 2010. Mayanagi H. Am J Physiol Lung Cell Mol background in Zimbabwe. a school-based survey. 60. Cross-sectional head and neck and esophagus: results of two multi. Communit Dent Health. e71122. 2007. Assessment national Association of Supportive Care in Cancer of dental caries predictors in 6-year-old school chil- (MASCC)/International Society of Oral Oncology dren – results from 5-year retrospective cohort study. Hiraki A. 47. Oral health in at 5 years of age? Communit Dent Oral Epidemiol. BMC Oral mary school children in Bangladesh. Childhood obesity 2008. 2004. Carolina Head and Neck Cancer Study. America: a report of the Surgeon General. Oral health issues for Ontarians: special report. Tooth decay in Ontario’s cancer risk in male health professionals: a prospec. Pediatr Dent. 2006. 2010. Smith J. Guha N. Hu XY. Acs G. Olshan AF. Wang RS.101(10):1900–6. 1992. de Soet school children from low socio-economic status JJ. van Gemert-Schriks MC. et al. 37. 50. children: an ounce of prevention – a pound of cure. caries and oral health practice among 12 year old Aartman IH. Schwarz E. Lancet. Effect 42. et al. Social inequalities in Göran Hansson B. Rosenquist K. Bhoomika W. Michaud DS. 2012. PLoS One. patients undergoing cancer therapy.

McCarron P. Nasseri P. 2011. de Oliveira C. Heart. Associations 83. 2004. 87. Walls AW. Heitmann BL. Yoshihara A. Role for 69.23:336–9. Nakano K. Miller SJ. Hokamura K. 2013. et al. Herzberg MC. rosis. J Pharmacol Sci. Taniguchi N. Nemoto H. Lind L.82:630–2. Airee A. Galobardes B. Tao prepubertal children. Finks SW. Henry M. 2011. 430–7.7. 77. Glodny B. 141–9. Recurrent loss and cardiovascular disease mortality risk – results Streptococcus mutans endocarditis. Am J Cardiol. Boganin C. 2007. Cunha BA. Skouteris H. 2010. Mattila KJ. Janket SJ. 2002.68:946–53. Lavstedt S. Watt RG. Is inflammation a con. Effects of oral flora on 762–8. Nomura R. Sanz M. 2003. et al. Zeng L. between periodontal disease and risk for atheroscle. 2005. The colla- 72. Frithiof L. Biochem Biophys rence of dental caries is associated with atheroscle. 86. Holm-Pedersen P. Lakkis NM. BMJ. human coronary artery endothelial cells by erosclerosis. Valtonen VV. Syst Rev. mutans strains and their correlation to virulence. 1989. Cohen W. Body mass index and dental caries in children and cariogenic Streptococcus mutans in extirpated heart adolescents: a systematic review of literature pub. Steele JG. and cardiovascular disease. Institute of Medicine. 7. Chow SL. tooth loss and mortality patterns in the Glasgow carditis by PCR amplification and sequencing. Heart Lung. Holt RG. Inaba H. valve and atheromatous plaque specimens.15: cases and review of the literature. periodontal disease. Res Commun. Am J Med. 1987. et al. Gilthorpe MS. Vose JM. Meyer MW. 2008. matrix molecules and fibrinogen.8:38–53. Tooth 76. Meurman JH. Gauduchon V. J Periodontol. Nomura R. Dental the United Kingdom.C. Matsumoto M. Paju S. Gerodontology. Jones MN.152 Z. cardiovascular disease. Sata N. Kaneko M.15:403–13.24:64–8. severe rheumatic heart disease. et al. Abranches J. Associations between diagnosis of recurrent Streptococcus mutans endo. diovascular morbidity and death among adult Danes. 93.113:120–5. Current and future directions of cardiovascular Microbiol Immunol. ath. 2012.22:7–11.32:54–87. Ling and H. 63. Ooshima T. et al. 2010. Smith GD. Roles of oral bacteria in cardiovascular diseases– rosis. Miller-Torbert T. 82. world: a critical challenge to achieve global health. Theobald H. Vayej AC.7:36–7. Crit Rev Streptococcus mutans OMZ175.28: 85. Crismani A. Promoting cardiovascular health in the developing 2006. Rose LF. Cardiovasc J Afr. Oral health of patients with disease. Pharmacotherapy. 2007. Invasion of 66. Hamada N. Nakano K.97:28–32.674 subjects followed for 12 years. Bridget BK. Strampfer MJ. Number of teeth as a 75. 2001. et al. 84. The occur. et al. Nicky 79. from the Scottish Health Survey. 67. Holm G.6:41–7. Scannapieco FA. Relationship Streptococcus mutans in infective endocarditis. Ann Relationship between oral health and mortality in Periodontol. Nomura R. The periodontal- in community-dwelling older persons aged 80 and medical risk relationship. Detection of K. Hooley M. Ullman RF. Nomura R. Horinouchi T. 2012.47:156–60. Binding of Streptococcus mutans to extracellular 71.21:57. Clinics. Qi M. J Periodontol. et al. Dokainish H.50:2021–8. 94. Oral health. Tu Y-K. Smith PW. 2012. Bush RB. Belanger M. J Med Microbiol. . 2001. Chen W. D. Jansson L.: National Academies Press. Hamer M. 2012. Tsakos G. cardiovascular disease and stroke: a systematic from molecular mechanisms to clinical cases: Cell- review. 88. Miyazaki H. Geriatric oral health issues in 74.28:289–95. et al.2:485. Holmlund A. 92. involvement of collagen-binding proteins of 73. Compend Contin Educ older: is there a link? J Am Geriatr Soc.298:779–81. 2001. Nat Commun. gen-binding protein of Streptococcus mutans is involved mation in initiation and perpetuation of atrial fibril. Avlund K. 1996.24:141–5. Benito Y. heart valve and dental plaque specimens from a 64. Molecular Jeffreys M. Potential J Am Coll Cardiol. Gamborg M.17:209–12. platelets: possible consequences in cardiovascular 70. periodontal bacteria in cardiovascular diseases. Association between dental health and acute myo. Oral 65. 81. Ann Periodontol. Isolation dietary interventions that influence cardiovascular and characterization of Streptococcus mutans in mortality. Celard M. caries. et al.51:183–7. 2011. Oral between root caries and cardiac dysrhythmia. PLoS One. 2001.81:870–6.298:75–9.45:441–5. and cardiac arrhythmias 90. Colan D. Kuramitsu HK. Nieminen MS. Immunol.93:1098–103. car- 78. 89. 2006. J Clin lished 2004 to 2011. Microbiol Infect. Naka S. Key articles of 80. Streptococcus mutans endocarditis: report of three Prev Med. Beg AM. Nomura R. Nemoto H. Clin Oral Investig. surface structures of novel serotype k Streptococcus 68.44:3313–7. 2009. et al.67:1138–42. Issac TT. Clin Alumni Cohort. Remaining teeth. Jsc S. Detection of Washington. Satur J. J Clin Periodontol. sequence or a cause of atrial fibrillation? Jpn Heart J. 2001. Nemoto H. 62. Dis. Int Dent J. 2009. 2006.53: Dent. oral bacteria in cardiovascular specimens. Minsk L. Morse DE. Nakano K. Maharaj B. Nakano K. 2013. 2004. Microbiol. Kang IC.55:1135–40. patient with infective endocarditis. Role of inflam. cardial infarction. Fuster V. 91. C-reactive predictor of cardiovascular mortality in a cohort of protein and atrial fibrillation. in haemorrhagic stroke. Oral Microbiol Oral Biol Med. 2010. lation: a systematic review of the published data. 1988. risk prediction. Nakano K.19:387–93. et al.

Klassen JT. B. JD. 2014. Shey Z. HIV infection. Pulpal inflammation and 116. review. editor. Low SH. 2011. (UNAIDS). Leao AT.85:996–1000. The Community Dent Oral Epidemiol. Liu G.6: JR. Michalek SM. Akagawa 212–6. Rodrigues incidence of coronary heart disease. 2009. Fundamental mechanisms of immune response with CD4 cell counts and viral load. Pediatr Dent. Caplan DJ. Murray PA. HIV infection affects Odontociênc. Stenvinkel P. Oral health in children with renal disease. J Endod. Mattos-Graner RO. from Streptococcus mutans in human dental caries. Rev 117. The dental health status of both mucosal and systemic immunity? In: Malamud dialysis patients. oral health status of children undergoing hemodialy- 110. Chopra M. Turk J Pediatr. p. Colditz GA. 2002. 2008. Houpt Gerodontology. Arch Oral Biol. 2013. Palumbo P.91:834–40. Akar GC. Gregory RL. Enterobacteriaceae and Pseudomonadaceae oral iso- 101. Nephrol. Dental caries in HIV-infected children. Brunelle J. Salivary immunoglobulin A and serum antibod. B. 2007. Sanui T. Lin YF. 1986. Chasen JB. Atherosclerosis. World Health Organization. Lambert HJ. Sahana S. Phelan JA. ment modalities in CKD patients in Taiwan. Woodhead J. Primo LG. Mulligan R. Jandinski J. Elbek-Cubukcu C. Höfling JF. Lindholm ies.9. J Dent Res. Frisk F. Lower dental caries prevalence AIDS. Wolff A. 1985. 119. Special report on HIV/ Maia LC. Braz J Oral Sci. 2006. Catalanotto F. Yoshimura O. endodontic origin and risk of coronary heart disease. Joint United Nations Programme on HIV/AIDS sis treatment. Antunes LA. 1996. Gonçalves lates from Brazilian HIV-positive patients. Hakeberg M. Brandtzaeg P. Yoshida M. Clin Rheumatol. Streptococcus mutans levels. 2012. Nunn JH. approach to control infections leading to dental car. Niedbala RS.24:361–8. in HIV-seropositive women. Jee 111. Hegde V. Soares RM. 99. Oral-based diagnostics. C. 2014. The vaccination J Dent Res. Guimaraes Primo 869–73. 2004. Peterson S. Ertugrul F. Howell RB. Plant ND. children versus household peers: two-year findings. Smith DJ. ies to Streptococcus mutans ribosomal preparations 123. Andrade MR. Bengtsson 115. Pediatr Dent. Sarnat H.56:1041–6.203:550–6. 1994.61:257–62. 108. Endodontic variables and coronary heart disease. Jadhav S. Pediatr Nephrol. Chen Z. Caries experience and cariogenic Atherosclerosis Risk in Communities Study. Phelan JA. Tofsky N. 106. McGhee chronic renal failure. Pediatr Nephrol.32:86–98. Drukker A. Dent Assoc.18:129–36. Querido SM. Back-Brito GN. Akar H. The relationship between self-reported history of 114. Dental caries in HIV-infected Acta Odontol Scand. e88418. J Oral Maxillofac Pathol.51:348–51. 113. Catalanotto FA. Ribeiro El Ackhar VN. Kao SY. Carrero JJ. sali- subjects.140:1004–12. 2003. Pizzo PA. Sabah E.14:997–1001. Kim YH.22:207–14. vary pH. Cai J. de Cássia Negrini T.6:218–26. endodontic therapy and coronary heart disease in the Feuerman M. Correlation RB. 2011. 2009. Geneva: Joint United Nations Programme on associated to chronic kidney disease: a systematic HIV/AIDS (UNAIDS). pediatric AIDS patients: a hospital-based study. Ahlqwist M. Willett WC. Pediatr 97. Coulthard Oxford: Blackwell Publishing. J Am markers in HIV-positive children and their siblings. J Can Dent Assoc.29:771–8.23:619–24. ponent of the Women’s Interagency HIV Study. . Do salivary antibodies reliably reflect 120. 100. Krasko BM. 288–311. MG. et al. PLoS sectional study. et al.61:114–8. 2003. Joshipura KJ. 2009. 122. Duque C. Filler SJ. Park JW. Murakami T.107:355–67. 2004. Pankow JS. Katz RV. et al. Baseline of Brazilian children and adolescents with chronic characteristics of participants in the oral health com.68:34–8. Siqueira WL. Houpt M. Pediatr Res. Sharp J. Gregory RL. The evaluation of oral health in stroke patients. et al. Lee S-Y.14:370–1. Lesions of Dent. 127–32. LSS. 2009. Salivary IgA antibodies to antigens Pediatr Nephrol. Valdez IH. 126. AIDS epidemic update. Mir S. 105. cine against dental caries: a brief review.8 Dental Caries and Systemic Diseases 153 95. Staphylococcus spp. editors.. Int J Pediatr Nephrol. 2000. Beck ASDC J Dent Child. Offenbacher S. 2004. renal failure. Y. 1992.31:247–50. Binderman I. Krishnappa SS. Hung H-C.45:108–13. 2000. Oral Microbiol Immunol. Krall EA. 2012. 118. M. Nelson EM. Stark H. Systemic consequences of poor oral health in 103. Nelson E. Dental caries 1985. The dental status of children with 107. Caplan DJ. 2009. Challacombe SJ. Chen JS. Eisenstein Adv Exp Med Biol. Tooth loss.17: 96. Huang RY. and salivary composition. Douglass CW.29:E489–93. Pitiphat W. Choe H. Oral and salivary flow characteristics of a group 109. A 104. Caries resistance in in dental caries-free and caries-susceptible human children with chronic renal failure: plaque pH. Analysis of Streptococcus mutans chronic kidney disease patients. 121. Mulligan R.32:99–103. D. Saxena D. Madigan A. 102. lin A.83: 124. One. but not genotypes. Salivary immunoglobulin A in rheumatoid expenditures for western medicine and dental treat- arthritis (RA) with focus on dental caries: a cross. Atkinson JC. 112. 1978.24:198–204.19:796–9. hypertension and risk for stroke in a prevalence of dental caries in children with perinatal Korean population. Shieh YS. 2006. to oral bacteria and the main perspectives of a vac. Clin J Am Soc biofilm proteins recognized by salivary immunoglobu. Martins C. Crall J. Fine DH. Venugopalan A. Krishnappa VS.3:595–608. 98. retrospective case–control analysis of the outpatient Chopra A. Lopez RN. et al. Kim SY. Oral health of J Dent Res. 2012. Infect Immun. 125.

Seow WK. Shepherd R. Stefanac SJ. dental caries. J Dent Res. Eur J Oral Sci. J Diabetes Complications. Tolentino MM. 158. Nedzelskiene I. related to the Pathol Oral Radiol Endod. in the albino rat. 2005. 148. Experimental dental caries Geneva: World Health Organization.S. Aust Dent J. Garton BJ. 2009. Saleh M. tooth loss in patients with diabetes mellitus types 1 155. Qader SA. Br J Nutr.22: 157. Periodontal dis- 94–8. 2006. diabetes mellitus. 141. 2007. Johansson I. Tumgor G. Centers for Disease Control caries-susceptible WBN/KobSlc rats. Root caries and diabetes: risk and 2. Siudikiene J. Ling and H. 2011. 129. Manz MC.100:190–200. Nagalingam NA.57:82–8.49:214–8. Salivary parameters and teeth erosions in 1 diabetics: influence of systemic factors of the dis- patients with gastroesophageal reflux disease. 1957. The diagnosis of root caries. Silvestre FJ. Nyvad B. Ford PJ. 2001. there an association? Degree Master of Science in 134. Dental caries and salivary status in disease: new oral findings. 130. Chongsuvivatwong V. Compend Contin Educ diagnosis and treatment of Gastroesophageal reflux Dent. Drake CW. Diabetes. Llambes F. Oral Surg Oral Med Oral children with type 1 diabetes mellitus. information on diabetes and pre diabetes in the 152. 137. on caries incidence in the albino rat. 2009. of colitis and colitis-associated colorectal cancer. Do root lesions tend to develop 138.57:114–22. Tao 127. Am J Manage Care. 2007. Ersin NK. Borgnakke WS. 147. Garcia RI. Seymour GJ. 2006. 133. Caries Res. 2011.11:9–20. Miralles L.47: and root caries. Risk calculation and comes. Wang W. Acta Odontol Latinoam. factors in children with type 1 diabetes mellitus. Banting DW. Fleury RN. Etzel KR. and tooth loss: 183–6. Stipp ACM. Cullinan MP. Matsuura M. et al. 1958. opment of dextran sodium sulfate-induced colitis.36:31–5. Machiulskiene V. 153. Trinchieri G. Tenovuo J. 2004. Aust Dent J. Caries.17:917–26. DeVault KR. Carlotto PR. Fu C.35:302–9. tistry. and minerals. 2012. Abayon M. 2008.25:179–92. 144. assessing to improve oral and systemic health out- 139. Oral Patol Oral Cir Bucal. Treatment planning in den- tes mellitus in China: a preventable economic bur. Twetman S. Spec Care Dentist. Comp Med. 151. Dental caries in type MA. Nesbit SP. Sci Rep. metabolic control of the disease. 156–62. Spec Care 159.12:286–92. 2003. Teanpaisan R. Wada K. Pomerantz SC. Shahid SM. Oncag O. disease. Aust Dent J. National injections of alloxan on the incidence of dental car- diabetes fact sheet: national estimates and general ies. 2009. 2012. Oral health in the elderly with on-insulin-dependent Community Dent Oral Epidemiol. 2011. 2002. Hintao J. 2001. Nakano K.36:68–74. Dent Assoc.28:279–84. Taylor GW. Ship JA. Kodama Y.25: periodontal diseases. 150. Root surface and coronal 140. Azhar A. Department of Health enhances dental caries and apical periodontitis in and Human Services. 2011. et al. Hernandez-Mijares A. Pediatr associated risk factors. Lawton FE. Med Gastroenterol. 1997. 132. World Health Organization. Kojima A.54:S62–9. Community Dent Oral Epidemiol. Oral 146. J Dent 142. Weyant RJ.91:301–10. Ship JA.61:53–9. Dahlen G. McGreevey WP. Young VB. Jawed M.19:8–14.134 Spec No:4S–10. Correa MCCSF. Nunn ME. Dental caries increments and related Inflamm Bowel Dis. Dental caries Educ. Diabetes and dental caries prevalence: is Nat Rev Immunol. Type 1 diabe- health of children with gastro-esophageal reflux dis. 2011. Medina in the same people who develop coronal lesions? Solis CE. periodontal outcomes. Damante JH. Rattarasarn C. Aydogdu S. Gastroesophageal reflux Nedzelskiene I. Am J Gastroenterol. Machiulskiene V. . Microbial 2006. Zielinski MB.114:8–14. Beck JD.50: 156. caries in diabetes mellitus: role of salivary flow rate 143. Nederfors T. Cunha Mde L. Birkhed D. 145. Linnett V. Diabetes: key facts.29:183–94. Sano T.65:991–6. 135.11:E256–60. Arq ease upon the development of dental caries. 1999. caries in adults with type 2 diabetes mellitus. in older adults with diabetes mellitus. the effect of single subcutaneous 136. Dent. Dental Dentist. Periodontol 2000. Diabetes and oral health: an overview. Innate immune mechanisms Caries Res. Ford PJ.15:593–601. specific strains of Streptococcus mutans. 149.21:127–33. Nyvad B. et al. Patino Marin N. Oral Caries incidence in young type 1 diabetes mellitus and dental manifestations of gastroesophageal reflux patients in relation to metabolic control and caries- disease in children: a preliminary study.154 Z. confers a risk of ulcerative colitis. Atlanta: U. Infection of Clinical Investigation University of Rochester. oral bacte. The effect of alloxan diabetes ria. ecology of the murine gut associated with the devel. 2008. Lin BP. et al. Castell DO. 2011. Centers for Disease Control and Prevention. Hartles RL. Allen DJ. 131. 2002. periodontal disease and J Public Health Dent.2:332. Shaw JH. Dietrich T. J Am 2009. Tenovuo J. and Prevention. Fedele D. Updated guidelines for the a review of the literature. Lerco MM. tes mellitus and oral health: assessment of coronal ease: a controlled study.42:354–62. Forman LJ. den. 65–77. Henry Bautista D. Moore PA. Type 2 diabe. Loyola Rodriguez JP. 128. Kao JY. Siudikiene J. Diabetes United States. 154. Taylor GW. Nichols MS. 2012. Grau D. Edinburgh: Elsevier Mosby. 2002. ease and systemic health: current status. Silva M. et al. 2001. Connor F.

Is there any rela- caries in adults with and without type 2 diabetes melli. Eldem I. tionship between dental caries and recurrent tus. 1999. J Oral Rehabil.30:105–10. Kaymaz N. Am J Dent. The relationship between infections mellitus. J Rheumatol. 2001. Alaki SM. 2010. Willumsen T. 2012:8–12 166. Soto- 1995. association with early childhood caries. The microbiological profiles of Dent. Association between dental caries and pneumonia in 1994. Root surface caries. Poster. respiratory infections in early childhood and their 164.68:340–5. Celis-Aguilar E. Tarzia O. Diabetol Metab Syndr. The microbiology and Periodontol. Aas JA. Oral health and respiratory infection.70:793–802. Grinde B. Mojon P. Sanchez-Guerrero J. Zambon JJ. Rojas AE. supragingival and subgingival plaque and dental 170. 2002.22:175–81. Hintao J. Oral Microbiol Immunol. Pascual-Ramos V. Pediatr Ratarasan C. J Can 171. Rheumatol J. 2008. upper respiratory tract infection? The 30th Annual 165. Jung DB. 168. Greeece. Role of oral bacteria in respiratory Dent Assoc. Ann 161. Teanpaisan R. J Clin Microbiol. Association of total tooth Meeting of the European Society for Paediatric loss with socio-behavioural health indicators in Infection Diseases. Ravald N.6:66–70. Jung SH.46:2015–21. 162.2:3. 163. Thessaloniki. J Periodontol. Bacterial profiles of root caries in elderly 169.8:323–8. 2006. Burt BA. . Dahlen G. Preza D.33:1996–2002. Middle ear and patients. Kasprzak SA.8 Dental Caries and Systemic Diseases 155 160. Chongsuvivatwong V. Korean elderly. 2008. histopathology of human root caries. Buccal alterations in diabetes 167. Negrato CA. Yazici H. Curr Opin Periodontol. infection. and chronic respiratory diseases: an overview. Ryu JI. Garetz SL. Terpenning MS.38:517–24. 2007. Olsen I. saliva. 2011. Hernandez-Hernandez C. Paster BJ.78–86. patients with systemic lupus erythematosus.

in vitro chemical models) and microbial West China Hospital of Stomatology. two basic methods are developed to study People’s Republic of China dental caries: de. Xuedong (*) State Key Laboratory of Oral Diseases. Less costly and comparatively rapid played a substantial role in caries research. In situ models in caries research Research 3.and remineralization in the teeth Department of Operative Dentistry and Endodontics. Xuedong (ed. Chengdu. and costly. more sensitive and precise tors contributing to the initiation and progression 3.. mostly related to their inability to simulate the in situ model. West China Hospital of Stomatology. Best approach to screen large numbers of agents of dental caries. and identify agents or measures and to determine their modes of action [5] with the ability to prevent or reduce the incidence of dental caries [2]. define the impact of numerous fac.1 In Vitro Chemical Models Z. Qiang • R.g. and animal model [3]. Biao • L.1. due to ethi. Sichuan Chemical induction of caries by organic acids is University. which are dental caries. Dental Caries: Principles and Management. Guo Qiang. which are G. Animal models in caries research In vitro models or laboratory models are the most Clinical trials are always large. Chengdu. DOI 10. tions. As dental caries results from an ecological H. (e. models have 1. In vitro models in caries research 9. some studies are not available in human subjects [1]. Models in caries research can However.g.and remin- e-mail: zhouxd@scu. Sichuan University. films. in vitro microbial mod- People’s Republic of China els) [6]. Ren Biao.1 In Vitro Models in Caries 2. and Zhou Xuedong 1. common models applied in dental research with consuming. Li Yuqing.. Models in Caries Research 9 Huang Xuelian. Xuelian imbalance in the physiological equilibrium State Key Laboratory of Oral Diseases.edu. Therefore. People’s Republic of China one of the principal approaches to study the © Springer-Verlag Berlin Heidelberg 2016 157 Z. furthermore. Sichuan University. several advantages [4]: cal problems. systems on the teeth (e. time.). which 2. between tooth minerals and oral microbial bio- Sichuan University. State Key Laboratory of Oral Diseases. People’s Republic of China 9. Yuqing closer to the tooth decay process in oral cavity. in vitro models have significant limita- be divided into three categories: in vitro model. microbial-based de. Can carry out single-variable experiments help to establish the multifactorial etiology of under highly controlled conditions.1007/978-3-662-47450-1_9 .cn eralization models are also developed. Chengdu. Chengdu. complex biological processes involved in caries. Recently.

The measurement of Tooth decay is the result of progressive mineral remineralization is used titrant [5]. cannot only decrease the amount of mineral and (3) assess the cariogenicity of carious diets. In details.) lattice ions and buffer titrants monitored potenti- ometrically by pH and/or calcium ion-selective 9.. for the reason that it ments or agents which are favorable to enhance demonstrated excellent correlation with the cur- remineralization. if the antimicrobial agents or measures. Xuelian et al. loss from dental tissues.and remineralization of formation but also change both the type and loca- enamel and dentin. 11].2 In Vitro Microbial Model Substrates are exposed to constant-volume super- saturated remineralization solutions. In vitro demineralization models enable researchers to examine those fun. techniques were involved: flow-through tech- tion models. Constant Composition Protocols however. particularly for ionic lesion repair and evaluating the efficacy of treat. their applicability is limited to factors Lattice ion concentrations and pH remain con- which directly influence the de. cycles of demineralization and remineralization. fluoride based dentifrices. latter. on natural enamel and tion is confined to substrate changes [5]. please also see “deminer. a particular in vitro remineral- 9. and it permits multi-group studies to be of substrates. fluoride. was recommended as an appropriate to investigate the mechanism involved in caries alternative to animal testing. which have become agents (e. because they provide better simulation inhibit enamel and dentin dissolution in acid of the caries process for both mechanistic studies attack.1.1 Demineralization Models electrodes was involved. two ization process. caries [6]. controlled addition of calcium phosphate alization and remineralization” part. “pH Cycling” Protocols damental processes. . 8]) or favorable choice to study remineralization the application of laser irradiation [9] which may in vitro. In vitro chemical models tion of mineral deposition [5.1. Different from remineralization former. Remineralization protocols can rently accepted animal caries models [12]. and their applications The “pH cycling” protocols consist of numerous include [5] mechanistic studies of solution/sub. stant throughout remineralization. Microbial models can be used to (1) cium and phosphate ion concentration will investigate prevention of carious lesions through decrease. (2) compare the systems are not well buffered. Between de. of modern pH cycling protocols was produced by and efficacy evaluation of caries-preventive ten Cate and Duijsters [10]. in remineralization solutions. The genesis of mineralized tissue to acid demineralization. including those pretreated and rem.1. carried out.1. means of a high volume of remineralization demineralization models utilize a wider variety medium. Recently. and the pH will also decrease. allow strict control of the experimental environ- ment and are relatively simple and cost-effective. and for evaluations of some caries-preventive agents. (For details. called Featherstone pH cycling In vitro remineralization models can be applied model. In the dentin [5]. natural products [7. substrates are one of the major niques and titration-controlled techniques. mechanisms in de.g.1.and remineral. studies which are correlated to alternant acidification and of factors contributing to the intrinsic resistance alkalinization phases in oral cavity.158 H.and remineraliza. supersaturation is kept constantly by methods which typically use lesions as substrate. They have In vitro microbial models provide means for the advantage of direct chemical measurement of studying complex microbial ecosystems on the remineralization within a given exposure period teeth and their roles on the development of dental [10]. In the differences. Those changes cariogenic potential of different microorganisms. cal. however.2 Remineralization Models ization model. The measurement of remineraliza- ineralized with agents. be grouped into three general categories: In pH-Lattice Ion “Drift” Protocol 9. strate factors affecting demineralization.

and Streptococcus oralis was cultivated to not easy to repeat the results.2.2 Closed (Batch) System microbial models for dental caries. was added later. Streptococcus sobri- [13]. However. less cost. incu. late its composition for experimental purposes.. fresh medium and for their ease of identification.1. This system is far from lum with a defined consortium has been con- physiological. A yeast species. Pure culture is broadly root caries model system developed in artificial used in vitro. Thirdly.2. This system enables Actinomyces naeslundii. possibility of fungal overgrowth due to selective Pure culture. provided with finite nutrients and growth rates are As the system is so complex. chosen for their relevance in health and disease In dynamic continuous system. and high throughput are bacteria in various combinations. however. Secondly. and the simplest and most frequently used in vitro interaction within the ecosystems. It is much easier to manipulate Streptococcus mutans. is comparatively rare in nature [13. In a are all used currently. dental plaque Microbial Models or saliva can be used.g. In from the bioreactor.1 Inoculum Candida albicans. furthermore form the caries lesion [20]. four putative root-caries pathogens. and microtiter plate . present. which was used to evaluate antimicrobial agents. and Lactobacillus rham- it is far from mimicking the oral cavity. inocu- fluid is regularly replaced. to find out a medium to support all organisms in in which there is no flow into or out of the reactor the plaque or saliva to grow as they do in oral cav- during the cultivation and microorganisms are ity. ments. form multispecies consortia biofilms and Microcosm is used to closely mimic the physi. normally done. it is more likely contaminated and nus. form supragingival plaque. Streptococcus sobrinus. 19]. and part of individual species can be added or deleted for the medium in the bioreactor is withdrawn from experimental purposes. Then some metabolites can be eliminated which is composed of nine bacteria [17]. Actinomyces naeslundii. It also allows detailed control and study of bation temperatures. it microbial models. cules and metabolites accumulate). they are often poorly characterized. During the growth process. in which physiological studies are mouth. 14]. classifications: closed (batch) system and open there are still some disadvantages. microbiological. the would have been difficult to standardize the plaque environment in the enclosed system will change inoculum in replicate experiments and to manipu- (e. the variation of the single test organism. signaling mole. and microcosm interference with bacterial ecology [18. nutrients become depleted. One of the good exam- the fermenter at the same flow rate of the inlet ples is often referred to as the “Marsh Consortium” flow. better control of growth rates and other variables Fusobacterium nucleatum. some small maintaining the complexity and heterogeneity and reactor vessels and test tubes were frequently enabling in situ bacterial community dynamics to used for planktonic culture. 15]. flows into the bioreactor continuously. In in vitro 9. composition shift. nosus. Firstly. it is hard and costly rapid. The closed system. Veillonella dispar. They have the advantage of In closed system microbial models. with organisms for initial screening assays [14. Those features make it valuable system more organisms in combination. less structed by pooling pure cultures of plaque contamination.9 Models in Caries Research 159 Microbial models can be divided into two main be replicated in laboratory environment. The communi- its marked advantages. however. and nutrient condi- tions present in oral cavity [13]. This system also allows ties that develop from them are stable with time researchers to easily vary multiple parameters and establish reproducibly in replicate experi- including the composition of growth media. However. for the reason An important factor in the design of in vitro that a valid prescreening test should rule out the microbial models is the choice of inoculum [3]. it is hard system (continuous culture). a mixture containing than batch cultivation [16]. It is to analyze its metabolism. subsequently. defined consortium. cochemical. and it is more like oral cavity another batch culture study. and O2 and CO2 concen.1. humidity. better repeatability. unless the In order to overcome these problems. 9. presence or the properties of the individual bacterial species absence of shear stress. Defined inoculum comprised of two or trations.

toner (magnetic (a) Custom-made stainless steel lid on which 24 clamps bead solution). The model consisted .160 H. enamel. Some modifications were developed for the 96-well microtiter plate. This model was once used ability of biofilm formation after 40. those disks are dipped in factor on dental caries [7. 12-. TSP is com- mercially available and contains a 96-well microtiter plate and a lid with 96 pegs placed on the plate. With this technology. inferring ture approach. and Candida albicans alization of bovine enamel under biofilms [18]. biofilms are either grown on the bottom and the walls of the microtiter plate (most commonly a 96-well microtiter plate) or on the surface of a substrata (glass. which confirms the repeat- image algorithms [14]. In MTP- based system. the immobi- lization of inert paramagnetic beads included in saline three times daily. during which transfer- able solid phase (TSP) biofilm model was used to screen antimicrobial activity [21]. 19]. The model could also Actinomyces naeslundii.1) was also used to eval- a salivary pellicle. a novel high-throughput active saliva-based medium on substrata coated with attachment model (Fig. and demonstrated biofilm formation in Streptococcus mutans [23]. [18. which provides a kit including microplates Fig. Substrata glass cover slips or HA disks are shown. 26]. 9. were similar to those observed in vivo. dedicated 24-well plate at the time of biofilm growth [25] block test (magnet support). Another MTP-based com- b mercially available method is the Biofilm Ring Test.1 Pictures of the biofilm model used in this study. Xuelian et al. and at each time point. a multispecies model.5 h and 64. contrast liquid (a nontoxic and are fixed. The former is generally based on bacterial sedimentation. At present. clinical testing of prospective antiplaque agents at six microorganism representatives are used to clinically relevant concentrations [24]. Veillonella dispar. is a classical batch cul. in which the metabolites accumulate. Actually. antimicrobial compounds. be used to achieve demineralization and reminer- Fusobacterium nucleatum. Biofilm can form on the surface of pegs through attachment. the the culture medium during the formation of the biofilms are dipped three times in saline. As shear forces are absent in a uate antimicrobial compounds and contributing batch culture system. (MTP)-based system is among the most fre- quently used biofilm model systems. and the latter can form a through attachment. 9. hydroxyapatite. (12 polystyrene strips of 8 wells). A magnet is used to collect being subjected to passages through an air-liquid the non-immobilized beads into a single spot interface [18]. and plate reader (scanner) [22]. (b) Position of the substrata (HA disks) in the inert opaque oil used for reading step). Cells are cultivated anaerobically in a More recently.5 h to confirm that AI-2-based quorum sensing affects in repeated independent trials. the produced losses in viability from brief expo- Zürich biofilm model. or dentin disks) placed in the wells of the microtiter plate (most commonly a 6-. generate biofilms for supragingival plaque. sures of biofilms to chlorhexidine or triclosan based on 24-well plates. in which the host of environmental that this biofilm model was very useful for pre- variables can be rigorously controlled. The validation of the in vitro caries which is then quantified through specialized model was assessed. thereby biofilm is measured. which the main application of this model was to evaluate are Streptococcus oralis. which is more close to the reality than the former. or 24-well microtiter plate). Streptococcus sobrinus.

whereby culture fluid is biofilm. flow cells can be device [28] (MRD. and from saliva can be formed in the systems [25]. in cases of high biomass within the flow cell [30]. used for flow cell construction do not respond well to autoclaving. formed on coupons (in some flat plate flow cells) in which green fluorescent protein was used as a or pegs (Robbins devices) [29].1. sterilization can be demineralization inhibition at the same time when difficult because many of the common materials bovine dentin disks were used as substrata [27].2) shared similar prin. real-time nondestructive microscopic analyses of cies biofilms and polymicrobial biofilm derived biofilms [14]. the design can be versatile in the selection of This model is also applicable for evaluating novel material for the substratum [30]. 9. Fig. Flow cells are species-specific marker [31]. the tube commercially available devices with glass can be plastic or metal.9 Models in Caries Research 161 Fig. into which pegs can be . 9. They still have caries-preventive agents on both biofilm and some disadvantages: Firstly. In MRD. Secondly. The co-adhesion of Streptococcus gor- passed through a tube or cell and biofilms may be donii with Streptococcus oralis was studied in a monitored microscopically (in flow cells) or two-species in vitro oral biofilm flow cell system. As Flow cell biofilm model and modified Robbins commonly used biofilm models. Finally. peristaltic pumps can produce System Microbial Models some pulsation in liquid delivery. This model is not inexpensive. it Flow Cell Biofilm Model and Modified is conceivable that a gradient in nutrients could Robbins Device be established over the length of the flow cell. used for single-species biofilm or multispecies ciples for the operation.3 Open (Continuous Culture) claving.2.2 Modified Robbins Media in device [28] Waste 14 µm filter Peristaltic pumps Side arm Bubble Waste trap Waste Modified Robbins Device (MRD) mounted on a hot plate (37 °C) Waste of a custom-designed lid containing substrata that chambers that are particularly well suited for fit on top of standard 24-well plates. especially to repeated auto- 9. Single spe.

the MRD is filled with a suspension in experimental design and in sampling because of microorganisms and is flipped over to improve medium flow over the surface of the slide may not the adhesion of the planktonic cells to the disks be uniform and hence there may be significant [14]. 34] Mininert top Needle Septum O-ring Bacterial air vent Coupon 10° Adjustable leg Effluent inserted so that when in place. defined consortium biofilm. which is from interproximal spaces beyond the reach of pumped through the substratum (a permeable . 200 or 300 μm Drip-Fed Biofilm Model is most commonly used for maintenance of den- Among drip-fed biofilm models. Fig. providing a low-shear environment with disper- sive mixing (Fig. drip flow biofilm tal plaques [13]. Perfused biofilm fermenters (PBF) are con- tory model to compare the potential effectiveness structed such that nutrients are supplied by con- of powered brushing to remove biofilm plaque tinuous perfusion of growth medium. 9. thereby and explore the etiology of dental caries [36. 37]. biofilms are fed by the drip-wise addi- The advantage of this system is that the biofilms tion of growth medium onto the turntable. In a typical as hydroxyapatite or teeth tissues. The biofilm devel- tem. or grown on angled slides continuously irrigated microcosm biofilm to evaluate antibacterial agent with small volumes of (inoculated) media. Care is required experiment. 9. through a waste outlet [13]. Different substrata can be used such forms part of the wall of the tube [13]. in which biofilms are species biofilm. This system can develop single- reactors are a simple sort.3 Schematic diagram of Influent a drip flow reactor [33. (CDFF). This system Perfused Biofilm Fermenters has been developed as an interproximal labora. In this system. a microorganisms [32]. This model was established as an appropri. and can be sampled by removing plugs at any time. the end of the peg bristles [35]. 34]. excess and/or spent medium flows downward once they are replaced to maintain a closed sys. Xuelian et al.162 H. the pump is aerial heterogeneity over the surface of the sub- started to allow a continuous flow of the growth stratum [13]. 33. situation mimicking the movement of the tongue over the teeth [14]. oped on a surface is limited to a predetermined ate biofilm model for susceptibility testing of oral depth by mechanically removing excess biofilm.3) [14. In constant depth film fermenter medium and biofilm development on the disks. After the adhesion phase.

cosm” [39]. and can be investigated (Fig. growth and development of dental plaque/biofilm yields relatively large amounts of biomass. 9. simulated . highly (spent culture fluid) [38]. multi-station the maintenance of complex salivary microbial artificial mouth systems.9 Models in Caries Research 163 Fig.4) [3. (b) longitudinal section of fluid line culture chamber Experimental treatments Sucrose line line Fluid delivery head Micro-reference pH electrode electrode Electrode and inoculation port Dental plaque Sample holder b Fluid delivery head port Thermometer Gas inlet Clamp Endplate Waste membrane) and hence through the biofilm [13]. 39. dur- grow oral biofilms by McBain and co-workers. oped by Sissons and his co-workers could be Disadvantages of MSD are related to the devel. It consists of a vessel in which a sur- The multiple Sorbarod device (MSD) is one kind face (or surfaces) is inoculated and supplied with of PBF which is proved to be an ideal system to a continuous or intermittent nutrient supply. real-time uses a simple two-piece stainless steel housing.4 Artificial mouth [39. plaque samples within a standardized. a (a) Cross-section of biofilm growth Screwcap with septum Simulated oral station. It has been validated for sophisticated. The advanced multiple ecosystems and for the in vitro reproduction of artificial mouth (MAM) system which was devel- interindividual variation within oral microbiotas. It ing such experimental procedures. This enables continuous monitoring of population system has progressed from simple and basic dynamics through the analysis of perfusates apparatus to the currently available. and dynamic steady states can be achieved. Artificial Mouth The media flow can be accurately controlled. employed for the long-term growth of multiple opment of heterogeneous biofilms [13]. computer-controlled. 40]. 9. the Artificial mouth models mimic the in vivo oral growth rate of the biofilm can also be well modu. 40]. niches and habitats to act as a laboratory “micro- lated.

and oral fluids and periodic pulses of animal or human model studies because of the sucrose to model meals were simulated. secondary caries. source of five species of oral bacteria grown in an eralization model” part in detail. The environment and possible only with this type of laboratory model. Bacteria also be used to inoculate a novel biofilm generat- can be grown at fixed growth rates. artificial “saliva-like” medium. A lot of medium Plaque samples grown over several weeks in this are needed. edly. if excessive bacteria grew in chemostat. the biofilm pH range can be controlled and manip. Nowadays.3 Microbial-Based De- Prevention of wall growth (change of cells from and Remineralization Model planktonic to biofilm forms adhering to the che- mostat vessel) is also very important. For analyze aliquots during plaque development with. this experiment could not have been performed in ulated. Besides. each containing Chemostat two types of surfaces in which plaque formed. primary caries. Herles and co-worker developed tors influencing the development of primary cari. ing model system. and molecular features to a very high into chemostat head and immersed in steady- degree of accuracy. These the organisms are not in a biofilm. This mixture was pumped through six flow cells. there are some modifications for chemo- interactions in simulated dental plaque and simi. stat to involve relevant surfaces to form biofilms. a chemostat flow cell system (Fig. of a predetermined depth can be generated [3]. 9. The applications of chemostat named defined medium with mucin (DMM). for the usual microbiology laboratory are costly which can work well as a “saliva substitute” [41]. and so on can be shifts within oral microbial communities [44] developed. Batch culture techniques can be used.5). chemostat can defined and controllable conditions [3]. the culture can also be sampled repeat. oral environment generated by computer. In this sys- consortium. form biofilm. the thin film fermenter. in which ous lesions and evaluate caries-preventive agents. the chemostat was provided with a continuous which will be represented in “microbial-based min. lar biofilms and monitor their physical. some modifications files typical of natural plaque.and remineraliza- cause deviations from “steady-state” growth tion model permits more clinical relevant in vitro [43]. tures are needed. inevitable pH change when carbohydrates are cally defined saliva-like oral fluid analogue is metabolized [3]. facilitating statistical analysis. which will The use of microbial-based de. tem. chemical. state planktonic cultures for certain periods [45]. of which a key feature is that biofilms lished. evaluating potential antimi. especially when multiple parallel cul- system exhibited metabolic behavior and pH pro. and later focus on pH-driven disruption [17]. S. Pure culture and mixed culture can both investigations of dental caries etiology and the grow in chemostat systems.164 H. under highly plaque agents [46]. however. in gle parameters to be varied independently so that which biofilms of a predetermined depth can be true cause-and-effect relationships can be estab. generated. pH at neutral values during sugar pulsing was controlled facilities [40]. 42]. and continuous culture techniques were also both of the two studies are very important to his applied in this system. enabling sin. Furthermore. 9. crobial agent [40. several artificial Chemostat has also been linked to flow cells to mouth models have been established to study fac. It was possible to are developed to alleviate the hurdles [43]. A chemi.1. pit and fis- gate carbohydrate pulses and pH on population sure caries. However. and have space considerations. Marsh developed a properties of caries-preventive agent. Chemostat can provide a homogeneous liquid and was subsequently used to compare the anti- environment for microbial growth. one of the shortcomings is that out contaminating the mature samples [40]. current applications contain evaluating microbial recently. classic chemostat. composed of nine bacteria to investi. root caries.” The control of mouth” was generally involved. during which “artificial “ecological plaque hypothesis. Xuelian et al. operational problems may arise from blocked tubing [3]. Sterile hydroxyapatite rods or disk can be inserted biological. .

the glycerin. to study the relationship of gap size and second. Subsequently. the teeth were infected with acrylic blocks with the tooth specimens were Streptococcus mutans in artificial mouth. These specimens were the process. and the removed daily. M. certain part of the tooth was slightly incubated at 37 °C and continuously washed with moistened (contaminated) with saliva to produce artificial saliva (pH neutral) at a regular rate. frice was applied for 3 min with a toothbrush.9 Models in Caries Research 165 Fig. This in vitro caries model contributed somewhat Katz and his colleagues developed a pit and to the study of pit and fissure caries including the fissure caries in artificial mouth.24 % sodium fluoride denti- secondary caries can be developed in contami. ulated pit and fissures with a concentrated When root tissue (disks) was used and puta- Streptococcus mutans inoculum. 15 % can be modeled in the bacterial system. E Flow C cells containing the HAP disks and germanium ATR Overflow prisms Vent Mixing chamber Flow cells (open view) Germanium prism HAP disks Flow cells (assembled) Waste In an in vitro secondary caries model. 9. stereomicroscopic evalua- ing shim stocks with different thickness at the tions revealed that the artificial lesions were very tooth/resin interfaces and Streptococcus mutans similar to those of natural pit and fissure caries. This model can also be used The latter procedure was repeated 5 days a week. Shu . weeks. B Vessel E containing a supply of A supplementary BM medium Supplementery (without glucose). and 0. A Chemostat Chemostet containing a mixed culture of B 5 oral bacteria. and the whole experiment was conducted for 8 ary caries. rated in toothpaste [40]. root caries overlaid with a nutrient layer of 15 % agar.5 Chemostat flow cell Flow cells system [46]. D The pump supplying flow (1 ml/ Modified BM media min) from the chemostat to 6 conteining mucin From flow cells low cells (1ml/min). The marginal gaps. during ficially created plaque. A filter paper and a occlusal surface of the tooth was sealed with a thin layer of collodion were placed over the arti- conventional resin-based fissure sealant. They selected study of remineralization due to agents incorpo- extracted human premolars and molars and inoc. which was tive root-caries pathogens were used. and 5 % sucrose. nated regions [47]. in which gaps were created by insert. was also used as inoculum [48]. C The BM media Mixed mixing chamber containing culture Pump D oral the flow from A (1 ml/min) microorganisms plus 5 ml/min from B.

plaque of varying composition and thick. 55] in human subjects without clinically relevant information in a relatively actually causing caries in the natural dentition short period without causing irreversible tissue [50]. Better control with the study subjects and bet. however. and therefore. For enamel. 51]: ods. the inclusion or exclusion of participants’ diet. These models attempt to provide ies prevention [54. saliva can also be used as inoc. 4. the micro- 1. mineral quantification methods [52. some of the results from other half used as the baseline lesion control [56]. in situ In remineralization study. By using in situ caries models. 56]. tion is raised as a question. changes in the natural dentition [50]. and Lactobacillus rham. and colleagues developed such root caries model population can represent the general popula- using four putative root-caries pathogens. such as to form artificial carious Research lesions [52]. For example. 2. These lesions can be sectioned to provide mals. animal caries models may not extrapolate to However. enamel surface. The validation of the studies is generally Actinomyces naeslundii. Whether the small study ferent teeth in the same mouth. may differ substantially depending on their The disadvantages of in situ caries model are design. as well as more applied research ances or devices which create defined conditions problems such as the effect of food on dental car- in human mouth to simulate the natural process ies and the role of caries-preventive agent in car- of dental caries. and a pellicle-coated tooth surface [50]. and the use of various allowing hypotheses to be tested. tages of in situ caries model systems compared a variety of intraoral sites. standardized demineralized lesions in laboratory while animal caries models are conducted in ani. Streptococcus sobrinus. heavily dependent on compliance of the test nosus [20]. They have fewer ethical and logistical problems. the use of mesh to 2. and enamel Compared with in vitro caries models. in vitro caries models. which is more suitable for for- mation of dental plaque biofilm [57]. They are less costly. the outcome of in situ caries models human beings. mouth [53]. When the in situ caries model was used to ness. on the same tooth .and remineralization. protect surface from mechanical disturbance and 3. to study de. enamel speci- which make it more close to oral cavity than mens were more frequently used than dentin.166 H. the choice of model may still obvious: significantly influence the conclusions drawn from such studies [58]. subjects.and remineralization. the presence of physiologically secreted baseline. The advan. tissue substrates. assess de. we have the potential to study both fundamental aspects of the 9. The number of subjects in in situ caries model bial composition of plaque will vary among dif- is generally limited. Due to so many differences between ani. dentin is useful to simulate root caries. ulum to develop the root caries [49]. one half lesion for the intraoral appliance and the mals and human beings. saliva. to encourage plaque retention. The results are acquired in much shorter time. Experimental design can be more flexible. which is suitable caries model is complicated by dietary eating for mineralization study [54] to make similar habits. Also. Both enamel and dentin can be used as hard 5. in situ slab (pieces of extracted teeth). both the natural ter compliance. Compared with animal caries model. can be used. In situ study designs are highly variable.2 In Situ Model in Caries caries process. with models using different hard tissue substrates. and to obtain dental biofilm directly in the human In situ caries models involve the use of appli. allow plaque accumulation. Xuelian et al. the use of different depth recesses and gauze 1. firstly. different exposure peri- with clinical trials include [1. Streptococcus mutans. it is better to produce caries models are conducted in human beings.

components of caries process. So the selection of patients for accumulate plaque. They have various forms: banding model such as orthodontic band model which can develop 9. 9. Orthodontic non-cavitated models can be roughly divided into two catego. and the effects of reminer- lenge. for after removing the band. The enamel can even be bonded to the teeth Nowadays. the lesion will Removable appliance is the widely used in situ not continue to develop [62]. It chlorhexidine. were involved. the model can be taken In 1995. which measure isolated R value but with a thin surface layer [52].2. In an in situ establishing the requirement that “all OTC anti- artificial dentin carious lesion study.2. in situ caries enamel surface [57]. They are invalu- teers dripped a 20 % sucrose solution on each able tools to simulate the natural progression of specimen four times a day for 14 days. Unlike in in situ model produced a deep lesion with a high situ and in vitro systems. immunological profile [3]. some new models were developed. If dietary Research challenges were not considered or oral hygiene is not the influence factor. 9. the caries under true biological conditions. destined for extraction. (white spot) lesion models have been used regu- ries: removable appliances and fixed appliances. This kind of treatment method can permit the testing of agents or proce- dures which might be harmful to the natural denti. to decrease vari. under plaque retention sites on the teeth that are The model can be exposed extraorally to the chal. the US Food and Drug Administration out of the mouth when subjects are eating or car. (FDA) issued the Anticaries Drug Products for rying out oral hygiene.1 Classification of In Situ orthodontic non-cavitated (white spot) lesion and Models can produce a plaque accumulation niche for demineralization. acrylic pala. ability in individual mouths. tion agents.1 Removable Appliances lesions. mens. Animal caries .9 Models in Caries Research 167 in different people. Fixed appliances in in situ caries model are the bial composition [59]. plaque-retentive areas below contact points [60]. and even on different surfaces grooves cut into bovine dentin disks was used to on the same tooth. and banding models [60]. caries dentifrice drug product formulations be tal appliances containing two bovine dentin speci. in either structure or micro. however. appliances that can only be removed in the end of the study. control and to diminish compliance. with desired micro. finally. single-section models.2 Fixed Appliances ble “natural” plaque. The crown single-section model In 1990. alization agents can be tested [56]. to give a high degree of Over-the-Counter (OTC) Human Use final rule. without chlorhexidine treatment can be well vary flow and buffer capacity. animal caries A removable appliance with three 200-μm-wide models truly measure caries [4]. which was later treated with in situ caries model should be carefully done.1. Also. larly for testing the efficacy of novel remineraliza- in terms of the mobility characteristic. Then the in situ plaque with and makes sense to recruit subjects with similar sali. The volun. plaque that forms with the aid of gauze does not fully resem. Wefel grouped in situ model systems relies mainly on placement of the sections in into three general types: removable appliances.1. this approach cannot be extrapolated to model other types of non-cavitated 9.3 Animal Model in Caries tion or ethically unacceptable [61].2. A special in situ car- caries model which can be constituted with acrylic ies model is that non-cavitated lesions formed appliances or denture and hard tissue substrates. investigated to extrapolate the similar conditions biological pattern. successful use in caries research. protected with a plastic mesh to allow Animal caries models have a long history of biofilm development. or to a therapeutic regime. directly to collect natural plaques on the natural and some models were less used. and even with a preferred in oral cavity [53]. tested in the animal caries reduction test” [12].

rats can be desalivated humans. The first recorded use of of microorganism in dental caries. Compared with in Sprague-Dawley rat. lower salivary antibody. including non. age of animals. In addition. present. some special putative anticaries traits. Comparing the lesion formation in germfree Animal caries models can be used to evaluate the and conventional rodents can make sure the role cariogenicity of diet. eating habits. indicating that caries excellent review [29]. When those consid. hamsters. litter effect. In short. saliva. and an model may show the effect brought by the experi. suggesting that there are multiple effects exerted by sIgA in Streptococcus mutans colonization. In mice with development of genetically modified animals targeted deletion of the gene encoding aquapo- makes utility of the model more broadly. extended life span compared to the parent strain. which lated rats. sex. while the pattern of which had their salivary glands removed surgi- caries in rodents is different from that observed in cally [29].1 Study on Etiology of Dental under the condition of sIgA and limited nutrients Caries on colonization in NOD/SCID. animals the role of diet in the etiology of dental caries. Animal caries models are very the roles of several salivary components in valuable to study the etiology of dental caries and Streptococcus mutans colonization in mice were evaluate the anticaries products. host can also be evaluated in genetically manipu- erations are deliberately under control.3. William H. and animal rats in caries research was published in 1922 by caries models are a good tool to study the micro- McCollum et al. and mice. and diet. In SPFOM rat. a sugar strain of Streptococcus mutans. mental factors. cariogenicity of milk and formula was involved in the pathogenesis of caries [3]. An alternative strategy is human primates. the animal caries hyposalivation. with synergistic effects evident 9. have enhanced our understanding of the impor- and the morphology of the teeth [2. several important susceptibility increases with a reduced salivary considerations should be paid attention to: selec. who was primarily interested in bial etiology of dental caries. model has played a critical role in caries research substitute. Xuelian et al. the host factors clearance of test compounds [3]. a water channel involved in the respect to the general considerations in animal production of saliva. The difficult to inoculate and establish some human incidence of caries increased significantly in rats bacterial strains in animals. it is diet was found to have higher cariogenic capacity the closest caries model.e2f1−/− [65]. flow that is associated with decreased water con- tion of animals. there investigated in animal caries models mainly are also limitations. Conventionally. In NOD/SCID. caries formation faster. Data from the animal composition of the oral flora and dental plaque. partially or completely by surgery to test the role Various experimental animal species have of saliva in the development of caries or to make been used in animal caries model. However. The interaction of bacteria and caging of animals. Bowen has a very increase in caries. 50]. The whole saliva is than pure starch [63]. there was a significant caries models. and it can provide components of the As the inherent difference in the dentition host defenses and simulate more accurately the between animals and humans. For model can be valuable in determining factors example. including differences on the focus on the saliva factor. Sucralose. so that this type of food was still evaluated by animal model. With rin-5 (Aqp5−/−). dentition. rats. It may be tance of saliva in maintaining oral health.168 H. food retention. which lacks .. evaluated. Nowadays. was found to have low cariogenicity in due to its unique advantages. high-glucose situ caries model and in vitro caries model. especially desalivated animal models. models. can be inoculated with mutants of cariogenic Most of the early studies were focused on the bacteria that lack putative virulence traits or have influence of diet [29]. during to genetically modify the test animal system to which the rodent models are the commonest. A compared in Wistar rat.e2f1−/− mice that show makes the baseline the same. The exclude the host factor of interest. tent of saliva [64].

4 The Role of Saliva in Caries Models 9. Stookey and co-workers Furthermore. HMA model is designed to assess the directly from the ingesta or from topical . This role is also demonstrated by animal caries model may be too severe to mimic a lot of clinical evidence. lesions. the other three models involve the infection supplemented with urea. 9. Also. while the urease genes of Streptococcus salivarius. and the response of animal car. In this process.K. the former mainly development of transgenic animals together with work on microorganism. Those are all important model. and bacterial metabolism of urea and use has failed in a rodent test. while desalivated adapted to colonizing and causing caries on animals (salivary glands are partially or com- smooth surfaces. However. even if there are still some differences among to evaluate the efficacy of fluoride-containing different individuals. agents. bacte- that no caries-protective agent currently in human rial cells. buffering and caries development. salivary peptides. the mechanism with fluoride. and the latter mainly genetic manipulation of microorganisms will work on mineralization. for those reasons: These mod. sobrinus. To overcome this problem. such as Francis’ hypomineralized it is better to recruit subjects with similar salivary area (HMA) model. and Indiana considerations in designing in situ caries study. salivary infection with S. salivary composition and flow differ at different ies models to fluoride demonstrates dose sites. Rats other three models utilize more overt caries were infected with the parent strain or the alkali. for example. the role of fluoride in saliva is have reviewed those models in detail [2].2 Evaluate Anticaries Agent The periods of alkalinization in dental biofilm. As antimicrobial agents utilize different tion inhibits caries [66]. the condition in human being. caries which resemble clinical caries structurally In in situ caries models. It is wise to modify the facilitate the utility of the model greatly and may animal caries model. it has arginine [66].9 Models in Caries Research 169 urease. rat caries model. was genetically engineered to express the impact on incipient enamel lesions. the role of saliva is been argued that the experimental conditions in very important. it is well realized that and etiologically. The outcome is that some prom. Gaffar’s CARA rat caries flow and buffer capacity. showing that alkali genera. mutans and fed a cariogenic diet flora. The rats infected with of the animals with cariogenic microorganisms. HMA model relies upon an indigenous producing S. which may lead to fluctuating results. So it responses [2]. can mimic the extreme cariogenic challenge com- Animal caries models have been demonstrated monly observed in patients suffering from sali- to be suitable to evaluate the caries-preventive vary hypofunction [64]. models to evaluate non-fluoride antimicrobial pared with controls. to alter gene expression in animals allow direct els develop incipient and more advanced coronal analysis of the saliva in caries development [64]. G. pletely removed or drug-induced hyposalivation) ising agents may be incorrectly discarded [3]. Connecticut rat caries model. It has been pointed out by salivary bicarbonate. are primarily attributable compounds and vaccination on plaque formation to diffusion of acids from the biofilms. lead to development of novel approaches to the prevention of disease [29]. and els. dentifrices. which is particularly factor is inevitably involved.3. is better to put the model in the same dentition There are several models that have been used site. in which the whole saliva is present. a In animal caries model and in situ caries mod- 56 % sucrose diet with ad libitum feeding. Fluoride may reach saliva speaking. The benefits of animal caries models also lie in which promote remineralization and restore the their role in evaluating fluoride and antimicrobial integrity of the enamel. the recombinant strain had a dramatically lower It is also possible to develop animal caries incidence and severity of all types of caries com. Furthermore. current techniques effect of fluoride. Shortly also well realized.

as a fluid with a complex chemistry that may In summary. fluoride in caries model. single. the microbial focusing on the saliva’s role in the oral cavity and nature of dental plaque. saliva plays a cru- bonate concentration and the velocity of the film cial role in the initiation and progression of den- of saliva in both thick and thin plaques. In some cases. However. particularly with respect and initial rapid clearance phase. or from temporary intraoral reservoirs of and some precursors for the adsorbed protein films fluoride. the saliva can to diffusion rates of acids into and calcium and have a low concentration of fluoride over long phosphate ions out of the enamel [71]. where the benefit of saliva is not working and Thirdly. there are some models colonization of teeth and. treatments. whether other caries-preventive glands. essary to consider this factor related to saliva. lyso- substrates. saliva has some properties regarding de. So it is nec. and ies of the Stephan curve showed that if salivary other basic polypeptides. chemical and physiological process of ing that salivary benefits can be exerted even with de. such as saliva. However. salivary clearance of bacterial in saliva which contain sialoperoxidase. found on teeth surfaces. favor the base formation and then the pH rise the effect of saliva was objected. via the salivary glands or gingival crevicular calcium-ion binding by salivary macromolecules. and polypeptides and proteins containing agents have their “reservoirs” in oral cavity. could play major roles in plaque pH homeostasis when evaluating the caries-preventive role of and in the inhibition of dental caries [66]. 70]. dental bio- thick plaques [67]. fluoride. may significantly influence the initial bacterial On the other hand. zyme. caries-preventive agents or measures is attributed ered to in many caries models.170 H. the reason may be attributed to its buffer that caries lesions form only in “stagnant” sites capacity [26]. therefore. After local application of fluoride eral with overlying fluids. arginine (or polypeptides and proteins) and urea. Fourthly. salivary proteins adsorbed onto sur- thus that models where salivary influences are faces of apatitic minerals profoundly affect bac- excluded will best represent the conditions of terial adhesion onto those surfaces. fluid. it is well demonstrated that alkali exposure to relatively high fluoride concentra. model plaque is highly dependent upon the bicar. which have a of calcium fluoride-like material and dental significant effect on the interactions of dental min- plaque [67]. ing of the etiology and initiation and progression cant ways [67]. generation from salivary substrates. the rate of pH rise in a antibacterial effect and also other bioactivities. Saliva possesses an array of of dental caries as well as the identification of activities that appear to have been seldom consid. tal caries. which have less specific stimulation is mimicked. film formation and metabolism. no bioactivities should not be ignored as the follow. much of our present understand- interact with the plaque and the teeth in signifi. aspects of caries. and so on. buffer Even in caries models considering the effect and neutralization of acid. in in vitro caries models. those to the findings of studies on models. especially tions for shorter periods of time [68]. histatins. the presence of saliva itself will saliva was not always emphasized. for the reason [72]. Xuelian et al. saliva tends to be considered in dental caries model. in oral cavity. of salivary factor. and different models have Firstly. arginine residue belong to saliva proteins. or indirectly from the bloodstream as the saturation of calcium and phosphate ions. and acid [69. the role of Interestingly. further on its role in dental caries. lactoferrin. indicat.and remineralization of the teeth. such have their advantage and disadvantage from both . Collectively. They and remineralization of hard tissue of teeth. Then another question is Arginine and urea can be secreted by salivary also raised. However. clearance. periods of time. which is as important as a brief Secondly. peroxidases. ideal model is optimal for studying all ing facts. specific roles in studying specific aspects. The stud. saliva should not be more as a nonspecific diluent or sink rather than ignored. including surface deposits on the teeth or pellicles. those effects caries lesion formation [67]. As a result. there are some antibacterial systems plaque interface.

9(3):244–54. An in vitro oral biofilm model for comparing the efficacy of antimicro- 1. Analysis of pH – driven dis- ruption of oral microbial communities in vitro. Microbiol. Cheng L. 13. In: Allen IL. In vitro and in vivo model sys. 1995. 2000. 2012. J Microbiol 6. Hoogenkamp MA.9 Models in Caries Research 171 experimental design and experiment cost.43(5):334–8. on demineralization and remineralization of the teeth: Bernardi T. McBain AJ.30:7. 2013. Effect of pH on Galla chinensis extract’s 24. Caries tion paper. ciated with alkali production from arginine in dental tion. bers for real-time study of biofilms. 5. Caries Res. The role of microbiology in models of Hartog AF. Caries Res. dium chloroperoxidase on planktonic Streptococcus 4. gival plaque. Exterkate RAM. J Dent Res.17(1):12–9. ten Cate JM. Featherstone JDB. Res.40(1): ical aspects of enamel remineralization – a constant 41–7. Renirie R. An in vitro microbial 23. Methods. 21. 2000. Clasen AB. Guggenheim B. Antimicrobial activity of vana- dental caries. Duijsters PPE. 1995. Jenkinson HF.57(8):1093–9.79(9):1725–30. mutans cells and Streptococcus mutans biofilms. J Dent. Marsh PD. Experimental intra-oral caries bial mouthrinses. 2009. Am J Dent. Bradshaw D. tor. Ten Cate JM. Kazmerzak KM. 31. Giertsen E. Huang X. model for studying secondary caries formation. Rodent model in caries research. Crielaard W. Talon R. Media. goals.36(2):93–100. Warrick JM. White DJ.9(3):208–13. Use of a modified 12.91(12):1130–4. Caries must be modified or refined to achieve the desired Res.24(5):289–94. 8. Guggenheim B. Liu Z. Stookey GK. Crielaard main component(s) on the prevention of enamel deminer. San Diego: Academic. DL1 and its use as a species-specific marker in coad- 16. Kaminski MA. Arch Oral Animal caries models for evaluating fluoride denti. Models 17. Guggenheim M.86(2):194–202. Ogaard B. faecalis biofilm formation. Nielsen J. Kinetic and phys. Shapiro stability and anti-caries properties in vitro. Lejeune P. green fluorescent protein in Streptococcus gordonii 2013. 2011. W. Hébraud M. biofilms. Development 1999. Villadsen J. Chapter 4: In vitro biofilm models: an 29. Bioreaction engineer. Caries luxS-based quorum-sensing signaling affects biofilm Res. Linton CJ. Adv Dent Res. Guggenheim B. Arends J. 160–6. Machado MAAM. 20. Deng DM. Huang Z. Sherriff A. Adv Dent Res. Dunipace AJ. 18. 1999. 2010.35(9): 9.9(3):198–207.66(9):4074–83. Exterkate RA. Lidén G. Adv Dent Res.57(6):334–41. 1998. 27. Appl Environ Microbiol. Arch Oral S. Jordan TH. Millar MR. 1995. ten Cate JM. Effects of low-energy CO2 laser irradiation and the 26. 2012. J Endod. Coenye T. Ma R. Marsh PD. Odontology. Jiang composition of Galla chinensis extract and the effect of its LM. Bowen W. 10.27(1):115–26.4(3):146–51. Gaillard-Martinie B. tems to study microbial biofilm formation. formation in Streptococcus mutans. Expression of the gut microbiome. Sissons CH. ten Cate JM. Animal caries models: reac. Fontana M. 2007. Recommendation for a non-animal alternative to Staphylococcus epidermidis RP62A to surfaces. editors. hesion with Streptococcus oralis 34 in saliva- ing principles. Geoffrey MG. J Mol Microbiol 7. New York: 30. Ten Cate JM. Miller LL. 1982. Li J. 2011. Wong L. Hoogenkamp MA. Experimental models of McNab R. Li Y. Tang Z. et al. Greene AL. 2012. 1995. Meric G. Gmür R. 2012. Exterkate RAM.22(1):11–9. Methods in enzymology. Biol. Chen WC. Hardegen N. Noblitt TW. Best Pract Res Clin Gastroenterol. p. J Appl rat caries testing.83(2):89–105. 99–132.16(3):201–10. demineralization biofilm model. Biotechnol. Aspiras MB. 28. of an active attachment model as a high-throughput 11. van den Abbeele P.38(3): 212–22. Influence of Streptococcus mutans on Enterococcus alization in vitro. Chavant P. Application lesions. Miller JH. Liu M. Zhou X.68(3):605–12. 2001. Park KK. et al. Stookey GK. Caries Res.32(6):456–62. Methods. Chemical 25. Venema K. Giertsen E. References 19. of multi-species consortia biofilms of oral bacteria as 2. 2009. Nancollas GH. Pereira AFF. Wever R. Huang X. Schüpbach P. overview. Shapiro S.101(1):9–14. Thurnheer T.45:14. Zhou X. Silva TC. p. an enamel and root caries model system. Liu M. Adv Dent Res. Huang X. 2004. Alternating demineral. 2000. Li J. film formation potential by bacteria. Application of the Zürich biofilm model to problems of cariology. 1988.9(3):194–7. models in fluoride research. 1249–52. New York: Springer Science + Business conditioned biofilms in vitro. 2002. Advances in applied microbiology. Dederich DN. 15. composition study. A new device for rapid evaluation of bio- reaction paper. J Microbiol 1999. The application of in vitro models to research 22. Nelis HJ. Caries Res. In: Ron JD. 2009. Wefel JS. frices. 3. Sima S. J Dent Res. Giertsen E. Stookey GK. Mundorff-Shrestha SA. Faller Robbins device to directly compare the adhesion of RV. 1996. Acta Odontol Scand. Kolenbrander PE. Shu M. . Bagnato VS.80(1):363–70. Int J Oral Sci. 2009. Microscopy flow cells: perfusion cham- Academic. Validation of an in vitro biofilm model of supragin- Biol. Gregory RL. van der Sluis LW. J Dent Res. Hsu C-YS. Palmer Jr RJ. Factors asso- organic matrix on inhibition of enamel demineraliza. ization and remineralization of artificial enamel Buzalaf MAR. edi- 14. Exterkate RAM.

Wiegand A. editor. J Dent. McNeill K. Wong L. Cochrane NJ. Chemostat 63. tions inhibits the progression of enamel subsurface 39.24(2):129–32.80(5):1436–40. 2004. J Dent Res. Effects of fluoride on caries development Robert KP. natural human plaque biofilms: a model for therapeu- lism. Comar LP. Yu stratum on the pH response of Streptococcus mutans H. Buzalaf MAR. WA. ten Cate JM. Effects of car. Bonass 41. 55. Robinson C. Zero DT. Xuelian et al. Advances in microbial physiology.172 H. Development of a flow method of antiplaque agents. Caries Res. J Dent Res. A multi-station dental plaque microcosm (artifi. Buchalla W. size and secondary caries. Arrest of root sur- 42.69 Spec No:626–33. Bizhang M.4(5):783–8.56(6): 43. 1995. Burne RA. In situ caries models. pH. McBain AJ. 46. APMIS. McGhee JR. De 54.18(4):e557–63. doi:10. Sissons CH. Caries Res. Sreenivasan PK. Tang G. 2003. The effects of sub. Samaranayake LP. Stoodley P. Role of urease enzymes in stability of a 10-species 53. discussion 34–6. and progression using intra-oral models. J Dent Res. J Dent Res. Am J Dent. Buckingham. Infect Immun. Shore RC. Afflitto J. Anderson SA. J Dent Res. Lagerweij MD. 2005. Walker GD. Deng DM. FEMS Microbiol tides — mechanisms of action and evidence for clini- Lett. 47. 2012. Preventing root caries development under oral biofilm ous flow. Standard test method for quantifica. 2012. Reynolds EC. artificial dentine carious lesions in vitro and in situ: dine. from interproximal spaces by powered tooth brush. J Dent.1038/nprot. In: Annual book of ASTM standards.36(4):270–4. A method for studying caries formation –development and ini- for growing a biofilm under low shear at the air-liquid tial testing.41(5): 31(3):194–200. The use of in situ models and QLF for the ing. Casein phosphopeptide-amorphous unique oral microcosms. 169–315. Zero DT.31:3.103(1–6):339–44.2009. Caries Res. Ostrom CA. 32. 2004. Roulet J-F. González-Cabezas C. Lai GY. Bacterial physiology. Calcium phosphopep- biofilm cells of Streptococcus mutans. Protoc. Pretty IA. Cochrane NJ.15 Spec No:12B–7. Kirkham J.24(2):41–7. 37. Meyer KA. study of coronal caries. 1748–55. 59. et al. Hamilton IR. challenge in an artificial mouth. Shu M. Med Oral Patol Oral 11. 2003. 2008. 44. Caries Res. Lo EC. Boston/Amsterdam: Academic. Buijs MJ. of a laboratory model to assess the removal of biofilm 51. Hamilton MA. Loetterle LR. Marsh PD. Int J flow cell system: an in vitro model for the evaluation Stomatol. Ten Cate JM. Chen Y-YM. Robinson C. 2012. Costerton JW. Moron BM. simulated oral environments. Cutress TW. Bowen WH.39:6.33:7. Development 1995. 58. Hoffman MP. Mass transfer of therapeutics through cial mouth) for the study of plaque growth. 2013. Ferenci T. Sissons CH. Wakefield lesions in situ. Confocal oral biofilm consortium cultivated in a constant-depth microscopy study of undisturbed and chlorhexidine- film fermenter. concentration fluoride gel and a fluoridated tooth- 1989. Caries Res. and mineralization. Totiam P. Remineralisation of bohydrate pulses and pH on population shifts within enamel lesions with daily applications of a high- oral microbial communities in vitro. . Adv Dent Res.47(2):162–70. 2002. Adams GG. Klück I. Caries Res. Cai F. Eur J Oral Sci. Cir Bucal. Edgar WM. Koulourides T.76(12):1845–53. eugenol on glucan is essential for the biofilm eradica.56(9):829–36. treated dental biofilm. Zaura-Arite E. Reynolds C.73(11): for susceptibility testing of oral biofilms in vitro. 1991. Feng J. Samaranayake LP.06. Mei ML.31:11. Higham SM.26(12):1152–5. 38. 1997. West Conshohocken: ASTM International. Hilyard JD. van Marle J.68(9):1298–302. Goeres DM.9(3):214–30.41:7. tional adaptation in a chemostat environment.2% chlorhexi. J Appl Microbiol. 1977. Oral Biol. Fiehn N-E. Animal model in caries research. Pluen A. 2007. A novel in vitro microbial-based model Meyer K. Adams H. J Dent Res. Different protocols to produce biofilms and on the susceptibility to 0. 1997. 40. A method for the quantitative White DC. Ledder RG. Nat Prod Res.112(1):42–7. 2001. 2002. Coleman MJ. Browngardt CM. 52. Ye DX. 33. 1990. Remineralization Artificial mouth model systems and their contribution models. p. paste: an in situ study.71(12):7188–92. 2006. Li MY. A new in vitro model to study the relationship of gap 34. Acid tolerance response of 62. Winston MT. Olsen S. Reynolds EC. Adv Dent Res. to caries research: a review. regulation and muta. 36. 2007. 2011. hardness and mineral content correlation. interface using the drip flow biofilm reactor. 2009. 2007. 61. cal efficacy. 2013. 50. Individual microflora beget Reynolds EC.44(1):33–40. Gaffar A.70(11): tic delivery to pathological bacterial biofilms. Adv Dent Res. Cutress TW. JSJ. The inhibition of face caries in situ. Wang J. Fejerskov O. In: 60. J Dent Res. 45. Vizio W. Bradshaw DJ. Larsen T. Microbiota of plaque microcosm biofilms: site-specific study of the biochemistry within dental effect of three times daily sucrose pulses in different plaque biofilms formed in vivo. calcium phosphate incorporated into sugar confec- 100(5):1123–31. Method E2647-08.221(1):25–30. Smith PW. 413–22. Loth J. Beck NA. Fontana MR. ten Cate JM. Shen P. Buckingham. 2003. McKee AS. Wefel JS. Zero DT. genic plaque in man. et al. a drip flow biofilm reactor with low shear and continu. 2010. Ten Cate JM. vol. Seemann R. Nyvad B. 57. Heersink J. Caries Res. Bizhang M. metabo. tion of a Pseudomonas aeruginosa biofilm grown using 49. 550–8. Nat 48. Chu CH. Yip H-K. 56. Brookes SJ. 1994. et al. 2004.59. Herles S. Arch 1409–16. Hickman F. 35. tion effect on caries-related biofilm in an artificial Microbial characterization of an experimental cario- mouth model. Gilbert P. Percival R.

Fallon MA. A mouse caries model and the effects of plaque thickness and initial salivary evaluation of Aqp5−/− knockout mice. animal model using NOD/SCID. Dibdin GH. .9(3):235–8. 72. Hay DI. salivary clearance. Adv Dent bacteria and protection against dental caries. Senpuku H. Caries-protective factors in saliva. Burne RA. dental plaque and its conversion to acid during 65. Marquis RE. 2012. A theoretical analysis of Pearson SK. J Dent Res. How to improve oral fluoride retention? mutans and the specific-plaque hypothesis. Maeda T. Caries Res.e2f1−/− mice. caries causation: an alternative to Streptococcus 68. Dawes C. 69. PLoS 70. Ito T. sucrose concentration on diffusion of sucrose into 2005. understanding the role of the oral bacteria in dental els. 66. Microbiol Lett. 2001. Oral Biol Med. Role of saliva in caries mod. 1995. Higham SM. FEMS Res.39(6):448–54.35 Suppl 1:14–7. Adv Dent Res.7(2). 2000. Roles of salivary compo. e32063.9 Models in Caries Research 173 64. Quivey RQ. 1994.8(2):229–38. 2002.9(3):239–43.13(2):108–25. Dent Res. 1995. Alkali production by oral 71. Crit Rev Caries Res. Sjögren K.65(2): nents in Streptococcus mutans colonization in a new 89–94.193(1):1–6. Lagerlöf F. Bowen WH. Edgar WM. Kleinberg I. Adv One. Faustoferri R. A mixed-bacteria ecological approach to 67. Salivary factors in caries models. Culp DJ. 1986.

37 Arteriosclerotic vascular disease (ASVD). 40 quaternary ammonium compounds. 141 ACP. 39–40 triclosan. 29 Amorphous calcium phosphate (ACP). 46–48 Acidogenic bacteria phenolic antiseptics. 40–41 (Bap) family ALL. 41 survival advantages of. 43 ADS. oris. 163–164 arginine deiminase system. 77 Biofilm-associated-protein (Bap) family. 139 Agmatine deiminase system (AgDS). 37. 112 Bacteremia. 42 Air abrasion. See Amorphous calcium phosphate (ACP) Arginine deiminase system (ADS). 42 Actinomyces ART. 29–30 clinical relevance of. Index A Anticaries agent. 42–43 Animal model Biofilm model de-/remineralization. 162 in research.). 42 concept and discovery. 165 Acute lymphoblastic leukemia (ALL). 161–162 anticaries agent evaluation. 160 © Springer-Verlag Berlin Heidelberg 2016 175 Z. 74 drip-fed. 79. 28 and biofilm ecology. 169 Academic Centre for Dentistry Amsterdam (ACTA). 42 Streptococcus mutans in. 169 Zürich biofilm model. 138–139 Adhesive dentistry. actinomycetemcomitans. 115 Aggregatibacter actinomycetemcomitans. See Biofilm-associated-protein urease. 44–45 Acid-etching technique. 42–43 formation. See Atraumatic restorative technique (ART) A. 44 ACFP. 39 Antimicrobial substances. 107.1007/978-3-662-47450-1 . 107 Atopobium. 160 saliva role. 46 Lactobacilli. See Amorphous calcium fluoride phosphate (ACFP) fluoride. DOI 10. in saliva. 32 open system microbial models. 45 Actinomyces. alkali production and. animal model. 46 acid tolerance of. 27 AgDS. 77. 47 Artificial mouth A. See Acute lymphoblastic leukemia (ALL) Bell stage. 43 Bap family. 39 Apical periodontitis. naeslundii. 28–29 in caries prevention. 111–112 B Air polishing. 169 systems. 168–169 TSP. 136–138 ADA caries risk assessment. See acidogenic bacteria. 167 flow cell. 3 Ameloblastin. 61 Amelogenin. 43 Amorphous calcium fluoride phosphate (ACFP). dentium. 65–67 Streptococcus mutans and. 40. 45–46 carbohydrate metabolism and. 160–161 etiology study. 50 Streptococcus mutans. 42 extracellular polymeric substances. Dental Caries: Principles and Management. Xuedong (ed. 115 Biofilm ecology. 39 xylitol.. 39–40 Atherosclerosis A. 7–8 Bifidobacterium spp. See Arginine deiminase system (ADS) Atraumatic restorative technique (ART). 49 Amelotin. 48 Atherosclerosis. 108 natural products. 29. 16 chlorhexidine. 131–132 Alkali production Bacterial biofilm ADS. 136 Antimicrobial approaches Accessory canals. 8 B. 8 Bicarbonate.

65–66 Chronic obstructive pulmonary disease Caries pharmacotherapy. and restorative dentistry. 105 Clin Oral Investig in 2011. 20 CBP. 112 Cytodifferentiation. 12 pit and fissure sealing. 112–113 CSP. 33. cross-sectional analysis of. See Center for Disease Control (CDC) British Medical Journal (BMJ). 101–102 Connective tissue fibers. 128 remineralization treatment. 134–136 Cardiac dysrhythmias. 4–5 . 75 tertiary prevention. 34 Candida albicans. 142. 105 slot preparation. 4 nonmachinery preparation. 135–136 CDC.V. 121–123 B lymphocytes. 115 Coronal caries. 50 sugar restriction and substitute for. 47 Cell-poor zone of pulp. 159–161 reinforce tooth resistance to acid. 143–144 dental plaque control. 3 mechanical rotary technique. See Cardiovascular disease (CVD) lasers. 137 CDFF. See Coronary heart disease (CHD) particles. 113 maturation stage. 113 Bitewing radiography. 114 CVD. 114–115 Bis-GMA system. 138 Chlorhexidine. 136. 91 Chronic kidney disease (CKD). 101 Community Periodontal Index (CPI) of FOTI. 111–113 secretory stage. 79 Childhood. 139. 142 CPP-ACFP. 44 Cardiovascular disease (CVD). 127–128 pit and fissure sealing. 157–158 stage. 115 origin of tissue. 79 Chemical models. 99 tunnel preparation. 105 CKD. 111–112 head formation. 114 (COPD). 136 primary prevention. 98 Closed system microbial models. dental caries. See Chronic kidney disease (CKD) preventive resin restoration. 114 C-reactive protein (CRP). 2 air polishing. See Transsal oral cancer. 113 presecretory stage. 145 Calcium fluoride particles. 159 Chemostat CaP. See Competence-stimulating peptide (CSP) enameloplasty. 113 Black. 77 CHD. 100 Collagen-binding protein (CBP). 138 Contact-microradiography. oral diseases. 140–141 CPP-ACP. 113–114 Biomineralization. 143–144 Caries-associated bacteria. 136–140 Chronic apical periodontitis (CAP). See Constant depth film fermenter (CDFF) Bud stage. 1–2 atraumatic restorative technique. 112 Camellia sinensis. 2 Ceanothus americanus. 103–105 CMCR. See Collagen-binding protein (CBP) Body mass index (BMI). See Ulcerative colitis (UC) DIAGNOdent. See Cetylpyridinium chloride (CPC) Cavity preparation CPP. 99 Treatment Needs (CPITN). 138 chemomechanical caries removal. 114 Bionics. 112 neural crest. G. 15–16 Cariogenic bacteria Constant depth film fermenter (CDFF). 91 QLF.. enamel development. in research. 73. 164 Carbonate hydroxyl apatite nanoparticles. 162 logistic regression analysis. 134 microradiography (TMR) Casein phosphopeptide (CPP). 79 Cetylpyridinium chloride (CPC). 77 Coronary heart disease (CHD). 149 Caries-preventive strategies Chronic renal disease. 17 C Center for Disease Control (CDC). 80 preventive resin restorations. 102–103 Circumpulpal dentin. 2–3 Chemomechanical caries removal (CMCR). 145 electrical caries monitor. 17 Cell-rich zone of pulp. 165 Carbohydrate metabolism. for caries detection. 100–101 Competence-stimulating peptide (CSP). 1 caries pharmacotherapy.176 Index Biological treatment methods. 38. 103 Confocal laser scanning microscopy (CLSM). 47 Chemoparasitic theory. 107–108 resin composite. See Casein phosphopeptide (CPP) minimally invasive treatment Craniofacial tissues embryology air abrasion. 86–87 conventional caries detection methods. 98–99 Colitis ulcerosa. 45 Calcium phosphate (CaP). See Chemomechanical caries removal (CMCR) secondary prevention Cold and hot irritation test. 5 microscopic preparation techniques. and restorative dentistry. 137–138 Care Index. 77 CPC. in research. 39 open system microbial models. See Calcium phosphate (CaP) flow cell system.

75 EDJ. 110 elastomeric separating modulus technique. 97–98 tooth loss and. See Dentin phosphoproteins (DPP) CPP-ACFP. 162 CPP-ACP. 168. 169 Dentin-enamel junction (DEJ). 133. 100 Demineralization models. 76 Electrical caries monitor (ECM). 88. 86–87 DMFT index. 87 Dental drilling. 31 fiber-optic transillumination. 97–98 Detection methods. 87 Dentinal tubules. 118 De-/remineralization DMFT index. 16. 34–35 medium caries. 77 DPP. 75 ECM. 85 as cause of dental caries. 75 Early childhood caries (ECC). 71 electrical impedance technology. 147–148 65–74-year-olds. 101 Dendritic cell. 133 diagnostic cavity preparation. 72 Elastomeric separating modulus technique. 88 enamel hypoplasia. 32 . 92–97. 94–98 Diagnosis for caries detection methods. 95–96 epidemiological studies of. 85 mineralization. 74 Electron microscopy. 30 inspection. 19–20 fiber-optic transillumination. 95 Diabetes mellitus (DM). 142 DIAGNOdent. 88. 33–34 lesion composition. 85–86 sclerosis. 91 dental fluorosis. 89 nonspecific/specific plaque. 72–73 Electrical impedance technology. missing. 9–10 Diet. 120–121 probing. 92. 87 Dental floss examination. 88 repair. 88 fluoride. 89 Dental microflora. 89 Dental fluorosis. 74 CLSM. 158 electrical caries monitor. 98–101 cold and hot irritation test. 85 Dentin predilection site. 78–79 35–44-year-olds. See Decayed. 34 percussion. 77 65–74-year-olds. 93. 12–13 staining technique. 95 laser. 75 eDNA. 88 prevalence. 102–103 symmetry of. 87 types. 142 dental floss examination. 100–101 5-year-olds. 88–89 bonding. 100 burden in China. 12 Diagnostic cavity preparation. 77–78 12-year-olds. 92–97. 73 5-year-olds. 101 investigations models. 87 animal model. See Enamel–dentinal junction (EDJ) TMR. 148–149 assessment. 87 enamel hypocalcification. caries research. 88 Dental enamel. 145–146 12-year-olds. 73 133. 88 and bacterial biofilm. 133 DIAGNOdent. and filled teeth biomineralization. 98 salivary immunoglobulin A. 34–35 QLF. 89 control. 77 Drip-fed biofilm model. 12 Direct bonding restoration technique. missing. 87 Dental plaque glossiness and smoothness. See Extracellular DNA (eDNA) dynamics process of. 12 quantitative laser fluorescence technique. and filled teeth (DMFT) index. 77 detection and measurement methods. dental caries. 9–12 ultrasonic technique. 75 E indentation techniques. 89 ecological plaque hypothesis. in vitro biofilm model. 36. 88 structure. 80 (DMFT) index calcium phosphate. 135 micro-CT. 31 progress of. 95–96 nanoparticles. 146–147 35–44-year-olds. 166. 96–97 root caries.Index 177 D in situ model. in pulp. 96–97 natural medicine. 99 Dentin phosphoproteins (DPP). 73–74 Decayed. 99 Dental caries quantitative light-induced fluorescence. 75–76 Ecological plaque hypothesis. See Electrical caries monitor (ECM) OCT. 103. 13 radiographic examination. 142 in vitro chemical model. 87 Nepal example. 7 Digitized fiber-optic transillumination (DI-FOTI). 94.

4–5 FOTI. 129 presecretory stage. 63 amelogenin. 142–143 salivary immunoglobulin A. 8 Head and neck squamous cell carcinoma (HNSCC). 158 importance. 2–3 tuftelin. 3 enamelin. 4 Focal sepsis theory. 119–120 Fluorapatite. 109 Enamel–dentinal junction (EDJ). See Fiber-optic transillumination (FOTI) enamel matrix proteins Fusobacterium. 76. 125–126 Fertilization. 169 Epithelial cell rests of Malassez (ERM). See Gingival crevicular fluid (GCF) histogenesis and morphogenesis Gelatinous microbic plaques. See Gastroesophageal reflux disease (GERD) cap stage. craniofacial tissues. 140 Human umbilical vein endothelial cells Environmental factors. 7. oral microbial ecology. 139 Environment dominates theory. See Head and neck squamous cell carcinoma Enamel rod. 87. 138 microstructure Gingival crevicular fluid (GCF). 141–142 Indentation techniques. 133 Enamel lamellae and cracks. 2–3 Gerodontology. 3 Genetic factors. in dental caries. 36 (HUVEC). 6 Human salivary lactoperoxidase (HS-LPO). 62 Endodontic inflammation. 142–143 Enameloplasty. 161–162 Enamel bonding. 28 Immune system disease Extracellular polymer substances (EPS). and smoothness. 8–9 Gastroesophageal reflux disease (GERD). 88. 167 origin of tissue. 32 enamel lamellae and cracks. 114 cytodifferentiation. 2 Film radiograph. 99 technology and material. 88 enamel spindle. enamel development amelotin. 5 Focal infection. 2 Enamel matrix proteins Hertwig’s epithelial root sheath (HERS). 130 secretory stage. bonding mechanisms. 6 functional aspects. 77. 2 GERD. 88. 105. 89 tooth loss with. 1 risk evaluation. 8 G enamelin. 8 HIV. 99 neural crest. 36 bud stage. craniofacial tissues. 1 Flow cell biofilm model. See Dental plaque bell stage. 73 HIV. in situ caries models. 8 bell stage. 16 head formation. 44–45. 6 Head formation. 3 saliva role in research. 6–7 H interpit continuum. oral microbial ecology. 7 bud stage. 47 enamel rod. 125 Fluorescence. 89 treatment. 126 . 114 HNSCC. 100 Enamel development Fluoride. 6 Head and neck cancer Enamel hypocalcification. 36 Hypomineralized area (HMA) model. 132 Erbium:yttrium-aluminum-garnet (Er:YAG). 5 Glossiness. 130 Extracellular polysaccharides (EPS). 2 proteolytic enzymes. 7–8 Histogenesis. 126 Fiber-optic transillumination (FOTI). 20–21 ameloblastin. 169–170 maturation stage. 49 IE. 118–119 I Evidence-based dental caries diagnosis. 5 (HNSCC) Enamel spindle. 6 Ginkgo biloba. 134 Enamel hypoplasia. 112 Essential oils. for caries detection. 132–133 Enamelin. 6 Human microbiome project (HMP). 47 Etching adhesive systems. 77 proteolytic enzymes. 7–8 amelotin. 7 Galla chinensis (GCE). 8 amelogenin. 8 GCF. 75 F Individualized treatment Featherstone pH cycling model. 8 Histatins. 30 Enamel tufts. 144–145 tuftelin. 36 ameloblastin. 8–9 cap stage. 28 effect on. 1–2 Fixed appliances. 21 Hyposalivation.178 Index Embryology of craniofacial tissues Fibronectin. 6 enamel tufts. See Infective endocarditis (IE) Extracellular DNA (eDNA).

77–78 slot preparation. 101 Microbial ecology. 113–114 Lasers preventive resin restorations. 37–38 Mesenchyme. 159 In vitro models. 20 pit and fissure sealing. oral microbiome. 16 nonmachinery preparation. 162–163 JAMA Otolaryngology–Head and Neck Micro-CT investigation. 161–162 modified robbins device. 19 Inoculum. 113 K Microtiter plate (MTP)-based system. 169 Mechanical rotary technique. 133 air abrasion. 50 prevention and effective intervention. 113 Inspection of caries. 112 remineralization treatment. casei. 110 Light active killing. 33 M Infective endocarditis (IE). 161–162 . de-/remineralization. 36–39 in pulp. 115 arginine deiminase system. 114 L. 163–164 microbial models. 20 disadvantages. 47 Interglobular dentin. 108–111 L cavity preparation Lactic acid bacteria. 47 lasers. in pulp. 37 Metagenomics. 162 flow cell biofilm model. 110 demineralized layer. 166 Matrix metalloproteinase-20 (MMP20). 159 classification. in pulp. 31. in research closed system. de-/remineralization. 114 L. enamel development. 73–74 Mantle dentin. 161–162 J perfused biofilm fermenters. 75 Microorganisms of the Human Mouth (Miller). 159 MAM system. 110 Lymphocyte. 21 and dental caries. 48–49 Intertubular dentin. 114 cavity preparation. 62 Modified robbins device (MRD). 9 Mineralization of dentin. 113 Lactoferrin. 157–158 inoculum. 111–112 Lactobacillus. open system 164–166 artificial mouth. 73. 113 Laminin. 20 factors involved in. 110 Lymphatics. 74 Microbial models. in oral cavity. 39 atraumatic restorative technique. 112 probiotics. 89 early diagnosis and personal treatment. 112–113 L. 89 infected layer. 5 saliva role. 166 Maturation stage. in pulp. 170 drip-fed biofilm model. 75 Surgery. 164 saliva role. 113 Lesion tunnel preparation. 11–12 Mesenchymal stem cells (MSCs) Interspecies interactions induction of differentiation. 133 Microindentation technique. 42 caries pharmacotherapy. 49 chemomechanical caries removal. See Matrix metalloproteinase-20 (MMP20) Lysozyme. 49 mechanical rotary technique. dental caries as. 10–11 Microbial-based de-and remineralization model. 66 air polishing. 164–166 QLF. See Slot preparation Minimally invasive treatment.Index 179 Infectious disease. 159–161 chemical models. 158–164 chemostat. 9 outcome. 112 acidogenic bacteria. in research. 110–111 progress of. 35–36 In vitro biofilm model. 33 Microscopic preparation techniques. 158 In vitro chemical model. 16 treatment and effective control. 49 enameloplasty. Intra-class correlation coefficients (ICCs). 110 symmetry of. 113 control. 2 metabolic interrelationship. 20 MMP20. 85 Melaphis chinensis. 111–113 Langerhans cells. microbial models. 73. 167 Mast cell. 63 microscopic preparation techniques. See Multiple artificial mouth (MAM) In situ model system de-/remineralization. reuteri. rhamnosus. 61. 114–115 de-/remineralization. 12 in research Marsh Consortium. 12 Mini box preparation. 138 Macrophage. 73 classifications. 159–160 Kallikrein-4. 159 microbial-based de-and remineralization model.

130 Multiple regression analysis. 105. See Multiple Sorbarod device (MSD) PCR method. enamel development. cariogenic bacteria and. 10. 148 lymphocyte. in research P. 37 “pH cycling” protocols. 161–162 Pulp. 40 morphologic zones of pulp. 2 cap stage. 22 Probing for caries. 48–49 dendritic cell. 49–50 Proliferative period. 94–98 proper. 62 Perfused biofilm fermenters (PBF). 78–79 material related factors. 92 ground substance. 124 National Health and Nutrition Examination Survey Porphyromonas gingivalis. 46 Pit and fissure sealant. 8–9 Olsenella. 130 mast cell. 163 Periapical diseases. 113–114 Plaque pH. 19 Oral cavity. 11 Mutacins. 20 CPITN. 43 flow cell biofilm model. 130 Oral microbial ecology. 91 odontoblast. 14–15 Presecretory stage. putida. 36 Pulpodentin complex Oral microbiology. 16 perfused biofilm fermenters. 12 bud stage. 85 Probiotics. 17 global policies. 163 Peritubular dentin. 129 nerve fibers. 16–17 Oral health. 14–15 epidemiological investigation in China. 105. 163–164 P. fluorescens. 138 MTP-based system. 4 Neural crest. 30. 129 Pulpitis. spatiotemporal development of. 75–76 dendritic cell. 43 Pseudomonas Open system microbial models. 16 Oral haemophili urease. 158 Myeloperoxidase (MPO). 12 Neisseria strains. 91. 140–141 General. 97 Periodontal disease. 15–16 Oral fluids. See Microtiter plate (MTP)-based Pediatric Nephrology. salivary influences on. 19 microbial ecology in. 15 uneven distribution. 62–63 bell stage. 20 Care Index. at early stage. 61–62 N Polymerization shrinkage. 161–162 accessory canals. 162–163 Multiple artificial mouth (MAM) system. 144 system Percussion for caries. 75 configuration factor. 162–163 cells in Optical coherence tomography (OCT). for root development. 91–92 fibroblast. 85 Mucins. 33 cells in dental pulp Oral microbiome. 13–14 modified robbins device. 29 drip-fed biofilm model. 134 Predilection site. 29 chemostat. 1 O Propionibacterium. 123–125 Nanoindentation technique. 88–89 Nerve fibers. 77 Predentin. 17–19 high-income industrialized countries. 134 macrophage.180 Index Morphogenesis. 31–32 lymphocyte. See Mesenchymal stem cells (MSCs) PBF. 19–20 Oral biofilms. 19 YLD/million population. 95. enamel development Oral microflora. 147 Postoperative sensitivity. 19–20 Oral microbiota. 3 Orthodentin. 20 . 92 mesenchymal cell. 125 Natural medicine. See Perfused biofilm fermenters (PBF) MSD. 149 Multiple Sorbarod device (MSD). 72 lymphatics. 16–19 Proteolytic enzymes. 124–125 Nanoparticles. saliva on. 114 Notch signaling. 2–3 Morphogenetic protein 4 (BMP4). 22 P MSCs. 29 artificial mouth model. 92–94 vascular tissues. de-/remineralization. See Optical coherence tomography (OCT) Propolis. 129–130. 35–36 connective tissue fibers. pulp. 36 (NHANES). 47 Odontoblast. 91 pulp fibroblast. 14 Oral Health in America: A Report of the Surgeon Pulpal periapical diseases. 43 OCT. 162 Pseudoramibacter. 1–2 Preventive resin restorations. 62 Phenolic antiseptics. 164 P. 20 Oral cancer. aeruginosa.

15 resin composites. 12–13 postprocessing decoration. 85–86 Wnt signaling.Index 181 macrophage. 88 cardiac dysrhythmias. 125 composition. 121–123 mesenchymal cell. 65–66 indications and contraindications. 121 types. 118–119 connective tissue fibers. 21 (QACs). 14 indications and contraindications. 125–126 xerostomia minimally invasive treatment (see Minimally invasive etiology of. 118 ground substance. 14–15 filling. and. 63–64 treatment) management of. 60–61. 13–14 technique sensitivity. 123 critical value. 12 polymerization shrinkage. 59 technique sensitivity. 119–120 pulp fibroblast. 128 animal model. 132 TGF-β/BMP Signaling. 120–121 Saliva.V. 125 sclerosis. 118–119 caries-associated bacteria. 19 etching adhesive systems. 61 requirements for. 75. 121–123 SAG. 15–16 silver amalgam lymphatics. 123 structure. 121 flow rate. 22 Radiation caries. 131 treatment. 123–125 repair. 125 low buffering capacity. 116 Rheedia gardneriana. 167 Resin composite bonding restoration technique S cavity preparation. 138 Quantitative light-induced fluorescence (QLF). 170–171 bonding technique and. 16 total-etch system. 59–60 postprocessing decoration. 127–128 fluoride. 115–116 nerve fibers. 73 enamel bonding. 118–119 dentin indications and contraindications. 21 signaling pathway R notch signaling. 13 postoperative sensitivity. 118 on plaque pH. 170 individualized treatment. 118–119 on oral microflora. in situ caries models. 121 characteristics and caries risk. 20 dentin bonding. 19 resin composite mast cell. 22–23 models in research. 116–118 vascular tissues. 68 postoperative sensitivity. 20–21 mesenchymal stem cells. 22 RA. 16 cavity shape preparation. 120–121 odontoblast. See Rheumatoid arthritis (RA) SHH signaling. 116 morphologic zones of pulp. 45 initiation. 119 pulp. 108 in situ model. 20 cavity preparation. 64–65 . 119 formation and secretion. 12 self-etch systems. diabetes. 169 direct bonding restoration technique. 61 total-etch system. 107 role in research based on bionics. 65 self-etch systems. 22 Remineralization tooth eruption. 107–108 oral cavity. 61–62 Respiratory infections. 61 etching adhesive systems. 67 polymerization shrinkage. G. 169–170 Black. 123–125 chemical and physical aspects. 158 16S rRNA gene sequencing. 147–148 100–101 Root development Quaternary ammonium compounds ERM. 119–120 carbonic acid/bicarbonate equilibrium in. 9–12 requirements for. 114–115 Removable appliances. 149–150 potential use of. 21–22 Radiographic examination for caries. 48 Rheumatoid arthritis (RA). 142 Q Root caries Quantitative laser fluorescence technique. 125 accessory canals. 129 Restorative dentistry. 17–19 enamel bonding. 121 mineralization. 118 in vitro models. 16–17 controversy. 62–63 Resin composites. 169 biological treatment methods. See Salivary agglutinin (SAG) dentin bonding.

32. 37. 42 Sanguinarine. 66 classification. for root SHH signaling. enamel development. 16 . 50 Transferable solid phase (TSP) biofilm model. 99 SIgA against. oralis. 37–39 V involvement. 168 Ulcerative colitis (UC). 88 Transversal microradiography (TMR). 38. 61 TRAP segment. 160 Staining technique. 127–128 Smoothness. 37.182 Index Salivary agglutinin (SAG). 38 salivary immunoglobulin A. 50 von Korff fibers. 7 atherosclerosis. See Severe early childhood caries (S-ECC) arginine deiminase system. 116–118 Tooth loss. 21–22 Tissue engineering. 39 Tunnel preparation. 4–5 Survey of Dental Diseases. 145 Salivary glands. 73. 110 Veillonella. 134 Slot preparation. 4. 87 ecological plaque hypothesis. 40. glossiness and. 66. 116 Tomes’ process. 50. 118–119 (STAMPs). 62 improvements in. salivarius. 62. parasanguis. 75 Stephan curve. 63. 119 Severe early childhood caries T (S-ECC). 130–131 indications and contraindications. 43 head and neck cancer risk. caries prevention. 42 Tyrosine-rich amelogenin peptide in artificial mouth. 115–116 TMR. 139–140 Secretory stage. 138–139 in biofilm. 161 Triclosan. 98 STAMPs targeting. 40. 42 Type 2 diabetes mellitus (T2DM). 42. 22 TGF-β/BMP signaling. 34 Vascular tissues. 45–46 S. 38. 33 Specifically targeted antimicrobial peptides Total-etch system. See Type 2 diabetes mellitus SHH signaling. sanguinis. 8 acidogenic bacteria. 165 interspecies interactions. 22 development. 140 Self-awareness. for root development. 37 Secretory IgA (SIgA). 113 acid tolerance of. gordonii. 38. 161 Sanguinaria canadensis. 14 risk assessment. pulp. 132 Tuftelin. 141–142 S. 42 Secondary dentin. 145 inoculum. 113 Tooth regeneration. 47 S. 88 Tooth worm. 63 strain of. for root development Technique sensitivity. 47 U colonization in mice. 31. 148–149 Slackia exigua. 29. 145 colonization in saliva. 43 S. 50 ulcerative colitis. 5 controversy. 165 (TRAP) segment. 61. 169 Scardovia wiggsiae. 135 T2DM. 125 notch signaling. 45. 34–35 Upper respiratory tract infection genetically modified strain. 98 Self-etch systems. 149 in GERD group. 143 Ultrasonic technique. 145–146 AgDS activity. 22 (T2DM) Signaling pathway. interspecies interactions. mutans. 21–22 TGF-β/BMP Signaling. 47 S. 127–128 Wnt signaling. 46 Salivary immunoglobulin A (SIgA). 68 Stroke. 22–23 filling. See Tyrosine-rich amelogenin peptide Streptococcus (TRAP) segment S. 116 diabetes. 160 catechins inhibit growth of. 12 interspecies interactions. See Transsal microradiography (TMR) cavity shape preparation. 168–169 Salivary antimicrobial substances. 132 S-ECC. 115–116 Tooth eruption. 141 Visual inspection salivary level. 20 Silver amalgam. 43 (URTI). 22 T lymphocytes. 132 xylitol.

92 medications. 133 sugar intake. 64–65 WHO Global Oral Health Programme. 22 severity of. 46 X Xerostomia causes of. 160 . 65 Xylitol. for root development.Index 183 W management of. 64 Z etiology of. 63–64 Zürich biofilm model. 64 Wnt signaling.