The Effect of Mesenchymal Stem Cells on Peri-implant Defect Healing in Animal Studies: A Systematic Review and Meta-analysis


  • Esthera Prateeptongkum, DDS., Dip., Institute of Dentistry,Department of Medical Services
  • Kannika Chukiatmun DDS., M.D., MsIT, Cert. in OMS Institute of Dentistry, Department of Medical Services


Dental implants, Mesenchymal stem cells, Tissue engineering, Meta-analysis


Background : The ultimate goal of peri-implant defect healing is the regeneration and establishiment of osteointegration. As the limitation of the autogenous bone graft which is considered to be a gold standard treatment, tissue engineering technique was created for an alternative treatment. Mesenchymal stem cells provide a promising approach for bone regeneration inducing and osseointegration enhancing with tissue engineering technology.Objective : The objective of meta-analysis was to quantitatively find out the effect of mesenchymal stem cells for peri-implant defect healing in animal model.Methods : PubMed database was systematically searched for related articles, together with searching in Google scholar. They were all filtered for articles in English or Thai from 2000 to May 2020.Results : Twelve articles, which are randomized controlled trials and preclinical animal trials were accepted and extracted for meta-analysis. Data was calculated for standard mean difference (SMD) at 95% CI and random effect model was used. the results showed that mesenchymal stem cell groups had positive results on bone formation (SMD=2.683; 95% CI= 1.580 – 3.786, p=0.000) and bone-to-implant contact (SMD=2.592; 95% CI = 1.363 – 3.821, p = 0.000). However, the data was high heterogeneity (I2=80.4%, I2=83.5%).Conclusion : The result evidences suggest that the mesenchymal stem cells might had benefits on peri-implant defect healing in animals. However, as less preclinical animal trials and possible the risk of bias problems, the further higher quality researches and randomized controlled trials in animal models are still required to prove the effectiveness of mesenchymal stem cells for the healing of peri-implant defect in clinical applications in the future.


Download data is not yet available.


Pjetursson BE, Karoussis I, Bürgin W, Brägger U, Lang NP. Patients’ satisfaction following implant therapy. A 10-year prospective cohort study. Clin Oral Implants Res 2005;16:185–93.

Albrektsson T, Zarb G, Worthington P, Eriksson AR. The long-term efficacy of currently used dental implants: a review and proposed criteria of success. Int J Oral Maxillofac Implants 1986;1:11–25.

Chiapasco M, Zaniboni M. Clinical outcomes of GBR procedures to correct peri-implant dehiscences and fenestrations: a systematic review. Clin Oral Implants Res2009; 20 Suppl 4:113–23.

Polyzois I, Renvert S, Bosshardt DD, Lang NP, Claffey N. Effect of Bio-Oss on osseointegration of dental implants surrounded by circumferential bone defects of different dimensions: an experimental study in the dog.Clin Oral Implants Res 2007;18:304–10.

Heitz-Mayfield LJA, Mombelli A. The therapy of peri-implantitis: a systematic review. Int J Oral Maxillofac Implants 2014;29:325–45.

Kao ST, Scott DD. A review of bone substitutes. Oral Maxillofac Surg Clin North Am 2007; 19:513–521.

Nkenke E, Neukam FW. Autogenous bone harvesting and grafting in advanced jaw resorption: morbidity,resorption and implant survival. Eur J Oral Implantol 2014;7 Suppl 2:S203-17.

Langer R, Vacanti JP. Tissue engineering. Science 1993;260:920–6.

Nishimura M, Takase K, Suehiro F, Murata H. Candidates cell sources to regenerate alveolar bone from oral tissue. Int J Dent 2012;2012:857192.

Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011;343:1-9.

Han X, Liu H, Wang D, Su F, Zhang Y, Zhou W, et al. Alveolar bone regeneration around immediate implants using an injectable nHAC/CSH loaded with autogenic blood-acquired mesenchymal progenitor cells: an experimental study in the dog mandible.Clin Implant Dent Relat Res 2013;15:390–401.

Hao PJ, Wang ZG, Xu QC, Xu S, Li ZR, Yang PS, et al. Effect of umbilical cord mesenchymal stem cell in peri-implant bone defect after immediate implant: an experiment study in beagle dogs. Int J Clin Exp Pathol 2014;7:8271–8.

Xu L, Sun X, Bai J, Jiang L, Wang S, Zhao J, et al.Reosseointegration Following Regenerative Therapy of Tissue-Engineered Bone in a Canine Model of Experimental Peri-Implantitis. Clin Implant Dent Relat Res 2016;18:379–91.

Ding L, Tang S, Liang P, Wang C, Zhou PF, Zheng L. Bone Regeneration of Canine Peri-implant Defects Using Cell Sheets of Adipose-Derived Mesenchymal Stem Cells and Platelet-Rich Fibrin Membranes. J Oral Maxillofac Surg 2019; 77:499–514.

Wang L, Zou D, Zhang S, Zhao J, Pan K, Huang Y. Repair of bone defects around dental implants with bone morphogenetic protein/fibroblast growth factor-loaded porous calcium phosphate cement: a pilot study in a canine model. Clin Oral Implants Res 2011;22:173–81.

Ribeiro FV, Suaid FF, Ruiz KG, Rodrigues TL, Carvalho MD, Nociti FH Jr, et al. Effect of autologous bone marrow-derived cells associated with guided bone regeneration or not in the treatment of peri-implant defects.Int J Oral Maxillofac Surg 2012;41:121–7.

Zou D, He J, Zhang K, Dai J, Zhang W, Wang S, et al. The bone-forming effects of HIF-1α-transduced BMSCs promote osseointegration with dental implant in canine mandible. PloS One 2012;7:e32355.

Yun JH, Han SH, Choi SH, Lee MH, Lee SJ, Song SU, et al.Effects of bone marrow-derived mesenchymal stem cells and platelet-rich plasma on bone regeneration for osseointegration of dental implants: preliminary study in canine three-wall intrabony defects. J Biomed Mater Res B Appl Biomater 2014;102:1021–30.

Xu L, Zhang W, Lv K, Yu W, Jiang X, Zhang F. Peri-Implant Bone Regeneration Using rhPDGF-BB, BMSCs, and β-TCP in a Canine Model. Clin Implant Dent Relat Res 2016;18:241–52.

Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327:557–60.

Park SY, Kim KH, Gwak EH, Rhee SH, Lee JC, Shin SY, et al. Ex vivo bone morphogenetic protein 2 gene delivery using periodontal ligament stem cells for enhanced re-osseointegration in the regenerative treatment of peri-implantitis. J Biomed Mater Res A 2015;103:38–47.

Mizuno D, Kagami H, Mizuno H, Mase J, Usami K, Ueda M. Bone regeneration of dental implant dehiscence defects using a cultured periosteum membrane. Clin Oral Implants Res 2008;19:289–94.

Misawa MYO, Huynh-Ba G, Villar GM, Villar CC. Efficacy of stem cells on the healing of peri-implant defects:systematic review of preclinical studies. Clin Exp Dent Res 2016;2:18–34.

Aerssens J, Boonen S, Lowet G, Dequeker J. Interspecies differences in bone composition, density, and quality: potential implications for in vivo bone research. Endocrinology 1998;139:663–70.

Muschler GF, Raut VP, Patterson TE, Wenke JC, Hollinger JO. The design and use of animal models for translational research in bone tissue engineering and regenerative medicine. Tissue Eng Part B Rev 2010;16:123-45.

Ribeiro FV, Suaid FF, Ruiz KGS, Rodrigues TL, Carvalho MD,Nociti FH, et al. Peri-implant reconstruction using autologous periosteum-derived cells and guided bone regeneration. J Clin Periodontol 2010;37:1128–36.



How to Cite

Prateeptongkum เ, Chukiatmun ก. The Effect of Mesenchymal Stem Cells on Peri-implant Defect Healing in Animal Studies: A Systematic Review and Meta-analysis. j dept med ser [Internet]. 2021 Jun. 18 [cited 2022 Aug. 14];46(1):89-98. Available from:



Original Article