Journal of Oral Biosciences 65 (2023) 13e18

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Journal of Oral Biosciences

journal homepage: www.elsevier.com/locate/job

Review

Human dentin materials for minimally invasive bone regeneration:

Animal studies and clinical cases
Masaru Murata a, *, Takashi Nezu b, Hiroaki Takebe c, Yukito Hirose d, Naoto Okubo e,
Takashi Saito f, Toshiyuki Akazawa g
a
Division of Regenerative Medicine, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Hokkaido 061-0293, Japan
b
Division of Biomaterials and Bioengineering, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Hokkaido 061-0293, Japan
c
Division of Histology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Hokkaido 061-0293, Japan
d
Division of Fixed Prosthodontics and Oral Implantology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Hokkaido 061-0293,
Japan
e
Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 13, Nishi 8, Kita-ku, Sapporo, Hokkaido 060-0819, Japan
f
Division of Clinical Cariology and Endodontology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Hokkaido 061-0293, Japan
g
Industrial Technology and Environment Research Development, Hokkaido Research Organization, Kita 19-jo Nishi 11-chome, Kita-ku, Sapporo, Hokkaido
060-0819, Japan

a r t i c l e i n f o a b s t r a c t

Article history: Objectives: Bone, platelet concentrate, and tooth-derived dentin/cementum have been used as autolo-
Received 20 October 2022 gous materials in regenerative medicine Dentin materials were first recycled in 2002 for bone regen-
Received in revised form eration in humans, although bone autografts were noted in the 19th century, and auto-platelet
28 October 2022
concentrates were developed in 1998. Dentin/cementum-based material therapy has been applied as an
Accepted 31 October 2022
innovative technique for minimally invasive bone surgery, while bone autografts are associated with
Available online 3 November 2022
donor site morbidity.
Methods: In October 2021, PubMed, Google Scholar, Scopus, and the Cochrane Library databases from
Keywords:
Human
1980 to 2020 were screened.
Dentin Results: The demineralized dentin/cementum matrix (DDM) had better performance in bone induction
Demineralized dentin matrix (DDM) and bone regeneration than mineralized dentin.
Bone regeneration Conclusions: Unlike cell culture therapy, DDM is a matrix-based therapy that includes growth factors. A
Graft matrix-based system is a realistic and acceptable treatment, even in developing countries. The aim of this
review was to summarize the evidence related to both animal studies and human clinical cases using
human dentin materials with a patch of cementum, especially DDM.
© 2022 Japanese Association for Oral Biology. Published by Elsevier B.V. This is an open access article
under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
2. Materials and methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
3. Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
3.1. Ectopic studies by human demineralized dentin matrix (DDM) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
3.2. Orthotopic studies by human demineralized dentin matrix (DDM) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
3.3. Clinical cases - DDM graft in humans e . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
4. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
4.1. Bone induction (ectopic studies by human dentin) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
4.2. Bone regeneration (orthotopic studies by human dentin) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
4.3. Clinical cases by autogenous dentin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
5. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

* Corresponding author. Fax: þ133231429.

E-mail address: murata@hoku-iryo-u.ac.jp (M. Murata).

https://doi.org/10.1016/j.job.2022.10.003
1349-0079/© 2022 Japanese Association for Oral Biology. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.
org/licenses/by-nc-nd/4.0/).
M. Murata, T. Nezu, H. Takebe et al. Journal of Oral Biosciences 65 (2023) 13e18

Ethical approval . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
CRediT authorship contribution statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Conflicts of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

1. Introduction This review aimed to summarize the evidence related to both

animal studies and human clinical cases using human dentin with a
Bone, platelet concentrates, and tooth-derived dentin/ patch of cementum.
cementum derivatives have been used as autologous materials in
regenerative medicine. A bone autograft was first reported in Italy 2. Materials and methods
in 1820. Platelet-rich plasma (PRP) was developed as an auto-
platelet concentrate in 1998 in the USA [1]. Extracted teeth have PubMed, Google Scholar, Scopus, and the Cochrane Library da-
been discarded as infectious medical dust worldwide. However, tabases were screened from 1980 to 2020 for this review in October
dental pioneers clinically applied patient-owned dentin for bone 2021, using the keywords of ectopic and orthotopic studies
augmentation in Japan in 2002, and the first clinical case was re- (“Demineralized dentin matrix” or “Demineralized dentin” or
ported by the International Association for Dental Research (IADR) “Dentin”) and (“Bone induction” or “Osteoinduction”) and (“Bone
in 2003 [2,3]. Importantly, dentin/cementum is biologically similar defect” or “Human”), and the keywords of clinical cases (“Demin-
to bone in its chemical composition. Fresh dentin and bone consist eralized dentin matrix” or “Demineralized dentin” or “Dentin”) and
of apatite (70%), collagen (18%; mainly type I collagen), body fluid (“Autogenous” or “Autograft”) and (“Bone regeneration” or “Hu-
(10%), and noncollagenous proteins (2%) in weight volume (Table 1) man”). Relevant full-length articles were obtained from the elec-
[4]. Dentin, bone, and cartilage contain bone morphogenetic pro- tronic databases and selected for review according to the following
teins (BMPs), whereas biomaterials such as ceramics and collagen inclusion criteria: (1) English articles in a peer-reviewed journal, (2)
do not include BMPs. animal studies that included any of the search keywords, and (3)
Regenerative medicine is based on the science and biology of articles that focused on bone regeneration. The removal criteria
applied biomaterials. Mesenchymal cells require anchorage-like were as follows: (i) Articles in which full text was not available and
scaffolds, whereas blood cells are independent of anchorage. In (ii) articles that were not related to human demineralized dentin
the field of bone regeneration, there is a medical need for bio- matrix (DDM) or human dentin. The selected articles were classi-
materials that allow for bone formation and can be gradually fied based on both ectopic and orthotopic studies and human cases.
absorbed by the body to be replaced by bone. Non-absorbable
materials can never be replaced by bone; thus, they cause chronic 3. Results
inflammation in living tissues as foreign bodies.
Organ recycling studies have recently become popular in tissue 3.1. Ectopic studies by human demineralized dentin matrix (DDM)
engineering. For example, decellularization technology enables the
transformation of organs into extracellular matrix scaffolds for Ectopic studies by human DDM are summarized in Table 2.
cellular anchorage [5,6]. Native dentin is originally an acellular
matrix. Demineralized dentin matrix (DDM) is highly acid-
3.2. Orthotopic studies by human demineralized dentin matrix
insoluble collagen with native cross-links, although commercially
(DDM)
available collagen materials have chemical cross-links. Dental pio-
neers believe that non-functional teeth are a native resource for
Orthotopic studies by human DDM are summarized in Table 3.
bone regeneration and recycled teeth as a novel graft material for
the self and their family [7,8].
3.3. Clinical cases - DDM graft in humans e

The autografts and familial grafts of DDM are summarized in

Table 1 Table 4. Several forms of DDM have been applied to sinus
Chemical components (wt/v%) of human dentin and bone.
augmentation, alveolar ridge augmentation, socket preservation,
Inorganic Organic Fluid BMP cyst cavities, and tooth transplantation. The dentin shell graft or
Dentin 70 20 10 þ tooth shell technique has been reported for horizontal alveolar
Cortical bone 70 20 10 þ ridge augmentation [29,30]. The DDM wall technique has already
Cartilage 2 28 70 þ been applied in implant placement [31]; we believe, therefore, the
Ceramics 100 0 0  dentin shell graft or the tooth shell technique should be in the
Collagen 0 100 0 
category of wall-type DDM application.

Table 2
Ectopic studies by human demineralized dentin matrix.

Year Authors [Ref.] Kinds of Dentin Bone Induction Recipient Preparation Acid

1998 M.Ike & M.R.Urist [9] 70 mg of PDM in gelatin capsule Root form e Normal/Nude mice Muscle 70% alcohol 0.6 N HCl
2010 M.Murata et al. [10] 70 mg of CDDM particles MDM particles þ (at 4 weeks)- Nude mice Subcutaneous 2% HNO3 (0.31 N HNO3)
2017 G.Rijal & H.I. Shin [11] CDDM particles MDM particles e Rat Subcutaneous 0.6 N HCl

CDDM: completely demineralized dentin matrix, MDM: mineralized dentin matrix.

14
M. Murata, T. Nezu, H. Takebe et al. Journal of Oral Biosciences 65 (2023) 13e18

Table 3
Orthotopic studies by human demineralized dentin matrix.

Year Authors Model Kind of Dentin Shape Acid Time Main Points
[Ref.]

2013 G.S. de Rat Tooth socket DDM Slice Covering on socket 10% EDTA 3 months DDM incorporated to new bone at 14 days.
Oliveira et al.
[12]
2015X. Qin et al. Beagle dog Periodontal defect DDM Plate (0.7  1.0 cm2) for 0.6 N HCl6 h DDM plate showed bone regeneration at 2 and 4 months.
[13] with periodontitis GTR
2016 T. Koga et al. Rat Parietal bone defect MDM DDM CDDM Size of 2% HNO3 0 min 5,10, 20 PDDM (size: 1 mm) induced prominent bone regeneration
[14] (∅ 6 mm) particles 200, 500, 1000 mm min 60, 120, 180 min at 4 and 8 weeks by CT.
2016 J.W. Nam et Rabbit Parietal bone defect DDM Particles 0.6 N HCl 15 h Space of 200 mm between particles was effective in bone
al. [15] (∅ 8 mm) formation.
2017 Md.A. Kabir Sheep Iliac bone defect (15  PDDM Root type (block) 2% HNO3 30 min Bone ingrowth into artificial pores and pulp space at 2 and
et al. [16] 10  9 mm3) 4 months by CT.
2017 S.M. Park et Rat Parietal bone (Removal of DDM Disk type (block) 0.6 N HCl 10 min (DDM/10) DDB/60 showed significantly increased new bone area
al. [17] outer cortical plate) (∅ 5  2 mm) 60 min (DDM/60) and bone density than DDB/10 at 8 weeks.
2018 R. Tanoue et Rat Parietal bone defect DDM Particles 2% HNO3 3 h Cellular processes of osteocytes extended into spaces of
al. [18] (∅ 6 mm) dentinal tubules by SEM.

PTFE: polytetrafluoroethylene, PCBM: particulate cancellous bone and marrow.

4. Discussion
4.1. Bone induction (ectopic studies by human dentin)
Animal-derived dentin was usually used for in vivo assays in the
20th century, and bone and cartilage induction were estimated
histologically. Subcutaneous tissues or muscles have been used for
bioassays of bone induction in extra-skeletal models of rats or mice.
Although granular dentin has been widely studied for bone in-
duction, several types of dentin materials can be prepared (Fig. 1)
[4].
In 1998, human partially demineralized dentin matrix (PDDM)
root and autolyzed, antigen-extracted dentin matrix were
implanted into the muscles of normal or athymic mice and failed to
induce bone formation, while PDDM with 1 mg of BMP-2 induced
bone formation [9]. In 2010, human completely demineralized
dentin matrix (CDDM; 70 mg) particles and mineralized dentin
matrix (MDM; 70 mg) particles were implanted into the subcu-
taneous tissues of nude mice (4 weeks old), and CDDM induced
bone and cartilage independently at 4 weeks, whereas MDM did
not induce bone and cartilage at 4 weeks [10]. The induced bone
was found locally on CDDM, and cartilage was observed between
CDDM granules. Interestingly, locally induced bone was formed
vertically towards the dentinal tube spaces [10]. The successful
bone induction might have caused the effective release of BMP
molecules from the wider dentinal tube spaces after 0.6 N HCl-
demineralization and the use of nude mice. Regarding the choice
of animal models, nude mice are ideal for assessing ectopic bone
formation because the immunocompromised nude mouse lacks a
thymus and does not reject human graft materials. The present
study selected subcutaneous tissues of the back skin for the
bioassay because 4 weeks old mice did not receive human CDDM
(70 mg) in the muscles. In 2017, human CDDM and MDM particles
were implanted into subcutaneous tissues of rats. However, CDDM
and MDM failed to induce bone [11]. An extremely low content of
BMP molecules in human dentin was considered as the main reason
for the failure of bone induction [8,10], although the types of
experimental animals and the preparation and form of DDM varied
for the abovementioned studies [9e11]. This prediction is sup-
ported by a report in 2017 that BMP-2 contents in MDM and PDDM

Table 4
Human clinical cases.

Year Authors [Ref.] Kinds of dentin Size Surgery Main points

2003 M.Murata [3] PDDM particles (0.5 Sinus augmentation Biopsy showing new bone and residues of PDDM at 5 months
e2.0 mm)
2006 M.F.Gomes et al. DDM slice (8 mm) Tooth socket covering DDM slice is better in healing than PTFE by radiographs
[19]
2010 J.Tazaki et al. PDDM particles (0.5 Immediate tooth graft with PDDM Crushed in electric mill
[20] e2.0 mm)
2013 J.Y.Lee et al. [21] Powder Block Mix Ridge augmentation 9 cases (male: 7, female: 2)
2013 Y.K.Kim et al. Powder (0.3e0.8 mm) PDDM grafts Socket preservation Sinus Biopsy showing new bone directly connected with DDM
[22] Block augmentation
2014 Y.K.Kim et al. Powder (0.3e0.8 mm) Familial PDDM grafts From daughter or son to Satisfactory outcomes. Biopsy showing new bone directly connected
[23] Block Mix fathers (2 cases) with DDM
2014 Md.A.Kabir et al. PDDM particles (0.5 1 cyst cavity 1 socket preservation Immediate graft Crushed by hammer
[24] e2.0 mm)
2014 Y.K.Kim et al. Powder (0.3e0.8 mm) Vertical and horizontal bone augmentation Safety report of 38,702 teeth (Jan.2009eOct.2012)
[25] Block
2017 T.Minamizato et PDDM particles 7 socket preservation 3 sinus augmentation 6 Immediate graft Biopsy showing new bone with PDDM
al. [26] alveolar augment.
2018 P.Li et al. [27] DDM particles GBR for implant placement 43 cases did not have any complications and achieved outcome after 1
year loading.
2020 I.W.Um et al. PDDM powder (0.3e0.8 Allogenic grafts Socket preservation with Retrospective clinical trial of 96 cases at 12 months. Successful results
[28] mm) implant
2020 M.Umebayashi PDDM particles (with Maxillary alveolar bone augmentation PDDM served as a scaffold for osteoblasts from PCBM. No complications
et al. [29] PCBM) for 4 years after final set.

PTFE: polytetrafluoroethylene, PCBM: particulate cancellous bone and marrow.

15
M. Murata, T. Nezu, H. Takebe et al.
Fig. 1. Types of dentin materials. From Ref. [4] in IntechOpen, with permission.
were 160 and 400 pg/g, respectively, by ELISA [33]. As the BMP-2
level in PDDM was approximately 2.5 times higher than that in
calcified dentin (MDM), PDDM and CDDM should have a better
performance in bone induction than MDM. Several studies have
reported that DDM/BMP-2 accelerates osteoblast differentiation
and induced bone [34e37]. In particular, CDDM/BMP-2 showed
36.3% at 4 weeks in the total volume of induced bone, cartilage, and
marrow, while CDDM alone showed 1.7% at 4 weeks by morpho-
metric analysis [34]. In vivo reports might support the synergistic
effects of BMP-2 and DDM-released growth factors for bone in-
duction in ectopic studies. In 2017, BMP-2 products such as BMP-2
delivered with an absorbable collagen sponge were approved by
the U.S. Food & Drug Administration as an alternative to autoge-
nous bone grafts for sinus augmentation and for local alveolar ridge
augmentation for defects associated with extraction sockets.
Collagen/BMP-2 and HAp/BMP-2 products are commercially avail-
able in the USA and EU [38] but not in Japan. In 2019, DDM particles
loaded with BMP-2 were used for socket preservation in 10 cases in
Korea [39]. In the near future, the combined use of DDM materials
and BMP-2 may be widely applied for minimally invasive surgery
and rapid bone regeneration.
4.2. Bone regeneration (orthotopic studies by human dentin)
Orthotopic studies include both inlay (bone defects) and onlay
(vertical and horizontal augmentation) models. Onlay grafts are
more difficult to form than inlay grafts because the supply of cells
and release of growth factors play critical roles in bone formation
and regeneration. In 2013, after the extraction of the upper second
molars in rats, the left alveoli were filled with DDM, and the right
16
Journal of Oral Biosciences 65 (2023) 13e18
alveoli served as the control. DDM was incorporated into new bone
formation after 14 days, and the results suggested that DDM acted
as a scaffold for osteoblast differentiation [12]. In 2015, the DDM
plate for GTR showed bone regeneration at 2 and 4 months in a
periodontal defect in a periodontitis model of beagle dogs [13]. In
2016, MDM, PDDM, and CDDM from human teeth were implanted
into rat calvarial bone defects. PDDM with a larger particle size
(especially 1000 mm) induced prominent bone regeneration at 4
and 8 weeks, probably because PDDM possessed a suitable surface
for cell attachment [14]. Additionally, in 2016, human DDM parti-
cles using 4 different particle sizes and densities (0.1 mL of
0.25e1.0 mm, 0.2 mL of 0.25e1.0 mm, 0.1 mL of 1.0e2.0 mm, 0.2 mL
of 1.0e2.0 mm) were implanted into rabbit calvaria bone defects
(8 mm in diameter). Histomorphometric analysis of the represen-
tative sections in the 0.1 mL of 0.25e1.0 mm group showed a higher
rate of new bone formation than that of the other groups at 2, 4, and
8 weeks [15]. In 2017, human PDDM blocks were grafted into
critical-size iliac defects in sheep (10  15  9 mm3). A non-
functional and vital wisdom tooth was recycled into a unique
geometric dentin scaffold, termed perforated root-type deminer-
alized dentin matrix (PR-DDM). Thirty artificial macropores (1 mm
in diameter) were added to the wisdom tooth after removing the
enamel and pulp portions, and the modified tooth was supersoni-
cally demineralized in 2% HNO3 for 30 min. The PR-DDM scaffold
was grafted into the critical-size iliac defect of adult sheep. Bone
ingrowth into the artificial macropores was observed at 2 months,
and the PR-DDM was connected to the original bone at 2 and 4
months. Micro-CT images revealed bone ingrowth into the pulp
space and union between the dentin scaffold and the native bone
[16]. Additionally, human dentin blocks demineralized for 10 or
M. Murata, T. Nezu, H. Takebe et al.
60 min in 0.6 N HCl were implanted into male rat calvaria as an
onlay model in 2017. The disk-type dentin block with 60 min-
demineralization showed significantly increased new bone area
and bone density compared to that with 10 min-demineralization
at 8 weeks [17]. In 2018, DDM was implanted into rat calvarial
bone defects, and a series of X-ray computed tomography images
were obtained over 12 weeks. Interestingly, the cellular processes
of the osteocytes extend into the dentinal tubules, and bone tissue
with canaliculi forms and fills the DDM surface [18].
Based on doctors' ideas for patients, several types of human
DDM (slice, plate, particle, powder, and block) have been used in
orthotopic studies and clinical cases (Fig. 1).
4.3. Clinical cases by autogenous dentin
The first autograft of PDDM particles was achieved for sinus
floor augmentation in 2002 and was reported in IADR 2003 [2,3].
The teeth were crushed in a stainless-steel vessel using a hammer
under cooling and demineralized for PDDM. In 2006, a DDM slice
was applied to cover the tooth socket, and the DDM slice healed
better than polytetrafluoroethylene (PTFE) on radiographs [19]. At
the beginning of this century, a new electric mill with a ZrO2 vessel
and blade for tooth crushing was developed in Japan [3]. The tooth
mill could crush the tooth into whole particles in only 30 s. In 2010,
tooth auto-transplantation with an autograft of CDDM particles was
reported [20]. Briefly, non-functional teeth were extracted and
cryopreserved immediately based on an orthodontic treatment
plan. The extracted teeth were crushed using a mill, and all particles
were completely demineralized in 2% HNO3 for CDDM before the
next surgery. Subsequently, premolars (#14) were transplanted
into tooth-lost regions with bone atrophy (#24), and CDDM was
grafted simultaneously for alveolar bone regeneration without
barrier membranes [20]. In 2013, powder or block type, or a mix of
DDM was applied for ridge augmentation [21], as well as for socket
preservation and sinus augmentation [22].
The tooth bank company was established in Seoul in 2009 for
preparing tooth-derived materials as a medical service (Korea
Tooth Bank, Co. Ltd.), and Seoul National University Bundang
Hospital opened a tooth bank facility in 2010. The two units re-
ported system safety in 2014, based on 38,702 teeth processed as
powders and blocks for 3 years (2009e2012) [25]. Familial teeth
were first recycled as DDM for alveolar ridge augmentation in a 45-
year-old man and for sinus augmentation in a 49-year-old man in
Korea in 2010 and published in 2014 [23]. In the second case, a 49-
year-old patient's wisdom tooth (#48) and 22-year-old son's
impacted tooth (#38) were prepared for autogenous and familial
DDM in powder form, and a mix of DDM was grafted to the father's
sinus bone augmentation in implant dentistry. Biopsy tissue at 3
months after DDM grafting showed active new bone formation. In
addition, autografts of DDM granules in Dhaka were first reported
in South Asia [24]. The extraction of the impacted tooth and the
autograft of PDDM particles were performed simultaneously for
bone regeneration after the extirpation of radicular cysts (#11,12)
and for bone healing in the extracted socket in Bangladesh. Dental
X-ray images obtained 1 year after surgery showed bone-like
radiopaque images in both cases.
In 2017, PDDM particles were immediately applied for socket
preservation, alveolar augmentation, and sinus floor augmentation
related to implant surgery (16 cases) [26]. Briefly, there were no
complications, and oral rehabilitation using dental implants was
successful in all cases for at least 2 years after attachment of the
suprastructure. In 2018, the efficacy and safety of autogenous tooth
roots and autogenous bone blocks were compared for lateral
alveolar ridge augmentation and two-stage implant placement
[27]. The tooth roots, the so-called root dentin without cementum,
17
Journal of Oral Biosciences 65 (2023) 13e18
supported lateral alveolar ridge augmentation, similar to cortical
bone blocks.
In 2020, a retrospective clinical trial of 96 allogenic DDM grafts
for GBR without a membrane achieved successful results 12
months after loading [28]. A 52-year-old patient received an
autograft of PDDM and particulate cancellous bone with marrow
(PCBM) for bilateral sinus floor augmentation and maxillary alve-
olar bone regeneration. There were no complications for 4 years
after the final restoration, and the PDDM particles served as a
scaffold for osteoblasts from PCBM [29].
5. Conclusions
Oral pioneers have been recycling dentin/cementum as novel
biological scaffolds for bone regeneration. Several types of demin-
eralized dentin/cementum matrices (DDM) are innovative mate-
rials that are based on doctors' ideas. Unlike cell-based therapy, the
application of DDM is a matrix-based therapy. This novel matrix-
based system is a realistic and acceptable treatment, even in
developing countries. For minimally invasive surgery, vital tooth-
derived materials that include growth factors might become a
worldwide alternative to bone autografts with morbidity.
Ethical approval
Ethical approval or informed consent is not required for this
review article.
CRediT authorship contribution statement
Masaru Murata: writing, literature search, data collection, study
design, writing. Takashi Nezu: data collection, data analysis, help of
submission, literature search, data collection. Hiroaki Takebe: ta-
bles, figures, data collection, data analysis, data interpretation.
Yukito Hirose: tables, figures, data collection, data analysis, data
interpretation. Naoto Okubo: data collection, data analysis, help of
submission, literature search, data collection. Takashi Saito: tables,
figures, data collection, data analysis, data interpretation. Tosh-
iyuki Akazawa: writing, literature search, data collection, study
design, writing.
Conflicts of interest
No potential conflicts of interest are disclosed.
Acknowledgments
This work was supported by a grant-in-aid for scientific research
from the Japanese Society for the Promotion of Science (Grant
No.20K10186) and a part by grant-in-aid for the 2019e2020
Research Project of the Research Institute of Health Sciences, Health
Sciences University of Hokkaido.
References
[1] Marx RE, Carlson ER, Eichstaedt RM, Schimmele SR, Strauss JE, Georgeff KR.
Platelet-rich plasma: growth factor enhancement for bone grafts. Oral Surg
Oral Med Oral Pathol Oral Radiol Endod 1998;85(6):638e46.
[2] Murata M. Autogenous demineralized dentin matrix for maxillary sinus
augmentation in humans: the first clinical report. J Dent Res 2003;82:B243.
[3] Murata M, Akazawa T, Mitsugi M, Um IW, Kim KW, Kim YK. Human dentin as
novel biomaterial for bone regeneration. In: Pignatello R, editor. Biomaterials -
physics and chemistry, Croatia. INTECH Publisher; 2011. p. 127e40.
[4] Murata M, Okubo N, Shakya M, Kabir A, Yokozeki K, Zhu B, et al. Dentin
materials as biological scaffolds for tissue engineering. In: Barbeck M, Jung O,
Smeets R, Korzinskas T, editors. Biomaterial-supported tissue reconstruction
or regeneration. Croatia: IntechOpen; 2019. p. 25e36.
M. Murata, T. Nezu, H. Takebe et al.
[5] Gilbert TW, Sellaro TL, Badylak SF. Decellularization of tissues and organs.
Biomaterials 2006;27(19):3675e83.
[6] Pina S, Ribeiro VP, Marques CF, Maia FR, Silva TH, Reis RL, et al. Scaffolding
strategies for tissue engineering and regenerative medicine applications.
Materials 2019;12(11):1824. 5.
[7] Kimura M, Murata M. Autotransplantation of teeth and decalcified dentin into
atrophied anterior maxilla. In: Murata M, Um IW, editors. Advances in oral
tissue engineering. Chicago: Quintessence Publishing Co, Inc; 2014. p. 43e5.
[8] Um IW, Lee JK. Familial tooth bone graft. In: Murata M, Um IW, editors. Ad-
vances in oral tissue engineering. Chicago: Quintessence Publishing Co, Inc;
2014. p. 67e72.
[9] Ike M, Urist MR. Recycled dentin root matrix for a carrier of recombinant
human bone morphogenetic protein. J Oral Implantol 1998;24(3):124e32.
[10] Murata M, Akazawa T, Takahata M, Ito M, Tazaki J, Hino J, et al. Bone induction
of human tooth and bone crushed by newly developed automatic mill.
J Ceram Soc Jpn 2010;118(6):434e7.
[11] Rijal G, Shin HI. Human tooth-derived biomaterial as a graft substitute for
hard tissue regeneration. Regen Med 2017;12(3):263e73.
[12] de Oliveira GS, Miziara MN, Silva ER, Ferreira EL, Biulchi AP, Alves JB.
Enhanced bone formation during healing process of tooth sockets filled with
demineralized human dentine matrix. Aust Dent J 2013;58(3):326e32.
[13] Qin X, Zou F, Chen W, Xu Y, Ma B, Huang Z, et al. Demineralized dentin as a
semi-rigid barrier for guiding periodontal tissue regeneration. J Periodontol
2015;86(12):1370e9.
[14] Koga T, Minamizato T, Kawai Y, Miura K, Nakatani Y, Sumita Y, et al. Bone
regeneration using dentin matrix depends on the degree of demineralization
and particle size. PLoS One 2016;11(1):e0147235. 21.
[15] Nam JW, Kim MY, Han SJ. Cranial bone regeneration according to different
particle sizes and densities of demineralized dentin matrix in the rabbit
model. Maxillofac Plast Reconstr Surg 2016;38(1):27. 5.
[16] Kabir MA, Murata M, Akazawa T, Kusano K, Yamada K, Ito M. Evaluation of
perforated demineralized dentin scaffold on bone regeneration in critical-size
sheep iliac defects. Clin Oral Implants Res 2017;28(11):e227e35.
[17] Park SM, Kim DH, Pang EK. Bone formation of demineralized human dentin
block graft with different demineralization time: in vitro and in vivo study.
J Cranio-Maxillo-Fac Surg 2017;45(6):903e12.
[18] Tanoue R, Ohta K, Miyazono Y, Iwanaga J, Koba A, Natori T, et al. Three-
dimensional ultrastructural analysis of the interface between an implanted
demineralized dentin matrix and the surrounding newly formed bone. Sci Rep
2018;8(1):2858. 12.
[19] Gomes MF, Abreu PP, Morosolli AR, Araújo MM, Goulart MD. Densitometric
analysis of the autogenous demineralized dentin matrix on the dental socket
wound healing process in humans. Braz Oral Res 2006;20(4):324e30.
[20] Tazaki J, Murata M, Yuasa T, Akazawa T, Ito K, Hino J, et al. Autograft of human
tooth and demineralized dentin matrices for bone augmentation. J Ceram Soc
Jpn 2010;118(6):442e5.
[21] Lee JY, Kim YK, Yi Y, Choi JH. Clinical evaluation of ridge augmentation using
autogenous tooth bone graft material: case series study. J Korean Assoc Oral
Maxillofac Surg 2013;39:156e60.
[22] Kim YK, Lee J, Um IW, Kim KW, Murata M, Akazawa T, et al. Tooth-derived
bone graft material. J Korean Assoc Oral Maxillofac Surg 2013;39:103e11.
18
Journal of Oral Biosciences 65 (2023) 13e18
[23] Kim YK, Kim SG, Lim SC. Familial tooth bone graft for ridge and sinus
augmentation: a report of two cases. J Korean Assoc Oral Maxillofac Surg
2014;40:37e42.
[24] Kabir MA, Murata M, Kusano K, Zakaria SM, Noor AHM, Khuda F, et al.
Radiological evaluation of human dentin autografts in Bangladesh. J Hard
Tissue Biol 2014;23:363e70.
[25] Kim YK, Um IW, Murata M. Tooth bank system for bone regeneration: safety
report. J Hard Tissue Biol 2014;23:371e6.
[26] Minamizato T, Koga T, Nakatani Y, Umebayashi M, Sumita Y, Ikeda T, et al.
Clinical application of autogenous partially demineralized dentin matrix
prepared immediately after extraction for alveolar bone regeneration in
implant dentistry: a pilot study. Int J Oral Maxillofac Surg 2018;47(1):
125e32.
[27] Li P, Zhu H, Huang D. Autogenous DDM versus Bio-Oss granules in GBR for
immediate implantation in periodontal postextraction sites: a prospective
clinical study. Clin Implant Dent Relat Res 2018;20(6):923e8.
[28] Um IW, Ku JK, Kim YM, Yun PY, Chang NH, Kim YK, et al. Allogenic demin-
eralized dentin matrix graft for guided bone regeneration in dental implants.
Appl Sci 2020;10:4661.
[29] Umebayashi M, Ohba S, Kurogi T, Noda S, Asahina I. Full regeneration of
maxillary alveolar bone using autogenous partially demineralized dentin
matrix and particulate cancellous bone and marrow for implant-supported
full arch reha-bilitation. J Oral Implantol 2020;46(2):122e7.
[30] Xiao W, Hu C, Chu C, Man Y. Autogenous dentin shell grafts versus bone shell
grafts for alveolar ridge reconstruction: a novel technique with preliminary
results of a prospective clinical study. Int J Periodontics Restor Dent
2019;39(6):885e93.
[31] Korsch M. Tooth shell technique: a proof of concept with the use of autoge-
nous dentin block grafts. Aust Dent J 2021;66(2):159e68.
[33] Bono N, Tarsini P, Candiani G. Demineralized dentin and enamel matrices as
suitable substrates for bone regeneration. J Appl Biomater Funct Mater
2017;15(3):e236e43. 27.
[34] Murata M, Kawai T, Kawakami T, Akazawa T, Tazaki J, Ito K, et al. Human acid-
insoluble dentin with BMP-2 accelerates bone induction in subcutaneous and
intramuscular tissues. J Ceram Soc Jpn 2010;118(6):438e41.
[35] Murata M, Sato D, Hino J, Akazawa T, Tazaki J, Ito K, et al. Acid-insoluble
human dentin as carrier material for recombinant human BMP-2. J Biomed
Mater Res 2012;100(3):571e7.
[36] Kim YK, Um IW, An HJ, Kim KW, Hong KS, Murata M. Effects of demineralized
dentin matrix used as an rhBMP-2 carrier for bone regeneration. J Hard Tissue
Biol 2014;23:415e22.
[37] Um IW, Ku JK, Kim YK, Lee BK, Leem DH. Histological review of deminer-
alized dentin matrix as a carrier of rhBMP-2. Tissue Eng B Rev 2020;26(3):
284e93.
[38] McKay WF, Peckham SM, Badura JM. A comprehensive clinical review of re-
combinant human bone morphogenetic protein-2 (INFUSE Bone Graft). Int
Orthop 2007;31(6):729e34.
[39] Um IW, Kim YK, Park JC, Lee JH. Clinical application of autogenous deminer-
alized dentin matrix loaded with recombinant human bone morphogenetic-2
for socket preservation: a case series. Clin Implant Dent Relat Res 2019;21(1):
4e10.