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E
XPERIMENTAL
F
ORMATION OF
P
ERIODONTAL
S
TRUCTURE
A
ROUND
T
ITANIUM
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MPLANTS
U
TILIZING
B
ONE
M
ARROW
M
ESENCHYMAL
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TEM
C
ELLS
: A P
ILOT
S
TUDY
Mona K. Marei, MScD; Manal M. Saad, PhD; Adham M. El-Ashwah, PhD; Rania M. El-Backly, MSc;Mohammed A. Al-Khodary, MSc
Tissue engineering in the head and neck area, presents numerous advantages. One of the mostremarkable advantages is that regeneration of only a small amount of tissue can be highly beneficialto the patient, particularly in the field of periodontal tissue regeneration. For decades, successfulosseointegration has provided thousands of restorations that maintain normal function. With theincreasing need to utilize dental implants for growing patients and enhance their function tosimulate normal tooth physiology and proprioception, there appears to be an urgent need for theconcept of periodontal tissue regeneration around dental implants. In the present work, 5 goats wereused for immediate implant placement post canine teeth extraction. Each goat received 2 implantfixtures; the control side received a porous hollow root-form poly (DL-Lactide-co-Glycolide) scaffoldaround the titanium fixture, and the experimental side received the same scaffold but seeded withautogenous bone marrow–derived mesenchymal stem cells. One animal was killed 10 dayspostoperatively, and the others were killed after 1 month. The results showed that on theexperimental side, periodontal-like tissue with newly formed bone was demonstrated both at 10days and after 1 month, while the control specimens showed early signs of connective tissueregeneration around the titanium fixture at 10 days, but was not shown in the 1 month specimens. Itcan be concluded that undifferentiated mesenchymal stem cells were capable of differentiating toprovide the 3 critical tissues required for periodontal tissue regeneration: cementum, bone, andperiodontal ligament. This work may provide a new approach for periodontal tissue regeneration.
Key Words: adult stem cells, periodontal tissue regeneration, immediate implants, tissueengineering
I
NTRODUCTION
A
n osseointegrated implant may closelyresemble a natural tooth; however, theabsence of periodontal ligament andconnective tissue via cementum resultsin fundamental differences in the adap-tation of the implant to occlusal forces.
Mona K. Marei, MScD,
is professor of prosthodontics and head,
Manal M. Saad, PhD,
is lecturer of oral biology and researcher,
Adham M. El-Ashwah, PhD,
is lecturer of oral surgery and researcher,
Rania M. El-Backly, MSc,
is assistant lecturer of restorative dentistry and lecturer, and
Mohammed A. Al-Khodary,MSc,
is assistant lecturer of prosthodontics and researcher at theTissue Engineering Laboratories, Faculty of Dentistry-AlexandriaUniversity, Egypt. Address correspondence to Dr Saad at TissueEngineering Laboratories, Faculty of Dentistry-Alexandria Univer-sity, 122 Port-Said St. #12, Ibrahimeya, Alexandria, Egypt. (e-mail:saad_manal@hotmail.com)
106 Vol. XXXV/No. Three/2009
R
ESEARCH
The character of the tissues around the titaniumimplant and the nature of the tissue attachment to theimplant surface influence the biomechanical respons-es of this integrated system. Because of this structuraldifference, functional differences also exist betweenteeth and osseointegrated implants.
1
In function, the mobility of an osseointegratedimplant is different from that of teeth, which mayresult in biomechanical problems when teeth andimplants are combined for the support of a rigidprosthesis. Although many investigators have recom-mended using shock-absorbing elements to simulatethe natural resilience of the periodontal ligament inthe implant or its suprastructure, others have pre-ferred to have anchorage of dental implants with thesame functional mobility as natural teeth.
2–4
In addition, physiologic migration of natural teethis a functional requirement of adaptation to maintaininterdental and interocclusal relationships—a charac-teristic that pertains to healthy periodontal ligamentand that it is impossible to achieve with dentalimplants.
5
Additional differences include the fact that thepotent cellular defense mechanism of the periodontalligament protects the tooth in case of inflammation, aphenomenon that does not exist around dentalimplants because of differences in the wound healingmechanism around a natural tooth with a periodontalligament vs an osseointegrated implant with directbone-to-implant surface contact.
6
In addition, the periodontal ligament has asensitive proprioceptive mechanism, which can detectminute changes in forces applied to the teeth. Forcesapplied to the teeth are dissipated through compres-sion and redistribution of the fluid elements, as well asthrough the fiber system. Forces transmitted to theperiodontal ligament can result in remodeling of toothmovement as seen in orthodontics, or in widening of the ligament space and an increase in tooth mobilityin response to excessive forces (eg, occlusal trau-ma).
7–9
In osseointegration, a greater level of bone contactoccurs in cortical bone than in cancellous bone, wheremarrow spaces are adjacent to the implant surface,which allows an initial period of healing after thesurgical procedures have been completed. This resultsin bone resorption and is followed by bone depositionover time. Although this is a dynamic process in whichbone turnover occurs, it is not an adaptive process, inthat the same happens with the natural toothsurrounded by a periodontal ligament.
10
Thus, the qualities of the periodontal ligament(PDL) from the anatomic and functional stand pointsprovide a number of potential advantages derivedfrom its presence on a dental implant (eg, for the useof implants in growing patients). This can offer thepotential application of dental implants for orthodon-tic tooth movement; hence, an implant with a PDLcould be moved orthodontically to optimized posi-tions so as to achieve more favorable esthetics andfunction.
11–13
Recent studies have shown the possibility of formation of periodontal ligament around titaniumimplants when a special model of application is used;this occurs when tooth-to-implant contact resultsfrom orthodontic movement or movement within anovel dentin chamber model. However, the methodsused were far from clinical applications.
5,14
In the present study, we investigated the possibil-ity of engineering a periodontal structure around atitanium dental implant placed immediately in a freshextraction socket in a goat experimental animalmodel. The tissue engineering principles utilized inthe present work included seeding of bone marrowmesenchymal stem cells onto biodegradable porousscaffolds to be placed around the titanium implantfixture.
M
ATERIALS AND
M
ETHODS
Three-dimensional (3D) hollow porous root-formscaffolds were prepared from 50:50 poly DL-lactide-co-glycolide (PLG) (Absorbable Polymers International,Pelham, Ala) with the use of the solvent casting/compression molding/particulate leaching technique,as described in our previous work.
15,16
PLG scaffoldswere prepared from 50/50 PLG with 1 g of salt of particle size 180–300
l
m. The hollow porous PLGscaffold was fabricated to fit around the fixture of theimplant, that is, a hexed-head, threaded, 3.75 mm,hydroxyapatite-coated fixture with mount universalhead diameter, and measuring 10 mm in length(IMTEC Corporation, Ardmore, Okla).A mold to serve as the initial iteration wasdesigned and produced out of Teflon. The dimensionsof the mold were estimated based upon the previousdimensions of the titanium dental implant screw. Themold consisted of an insert, a hollow tube, and a solidcylinder (Figure 1a and b).In forming the scaffold, the PLG with the saltparticles was placed in the tube and was pressed, andthe flat end of the solid cylinder was used to press thePLG between the end of the insert and the flat end of the solid cylinder (Figure 1c). This procedure wouldconfirm a standardized size, length, and width of thePLG scaffold each time (Figure 1d and e).
Journal of Oral Implantology
107
Mona K. Marei et al
F
IGURE
1.
Prototype of designed Teflon mold used to produce hollow porous scaffold around the dental implant screw. (a) The dimensions of the insert and the tube. (b) The insert, the hollow tube, and the solid cylinder with a flat surface. (c) The three parts as they are used (leftside of photo) and the hollow Teflon tube, with insert inside showing the space to be occupied later by the DL-Lactide-co-Glycolide (PLG)scaffold (right side of photo). (d and e) The PLG scaffold at the end of the insert as it comes out after molding.
108 Vol. XXXV/No. Three/2009
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