The Effect of Cell Sheet Engineering for Periodontal Tissue Regeneration in Clinical Studies: A Systematic Review and Meta-Analysis


  • Esthera Prateeptongkum, DDS., Dip.,


Periodontal treatment, Cell sheet engineering, Osseous defect, Meta-analysis


Background : The ultimate goal of periodontal treatment is the regeneration of damaged periodontal tissue. Currently, cell sheets with “Cell Sheet Engineering Technology” were created for the alternative periodontal tissue regeneration. According to the easy fabrication and manipulation, the use of cell sheet technique offers more interesting in clinical setting.

Objective : To quantitatively find out the effect of cell sheet technique for periodontal tissue regeneration in human.

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 1990 to 2019.

Results : Four articles, which are randomized control trials, clinical trials, and case series were accepted and extracted for meta-analysis. Data was calculated for weighted mean difference (WMD) at 95% CI and random effect model was used. The results showed that the cell sheet technique approach had positive results on clinical attachment level (WMD = -3.080 (95% CI -4.697 - (-1.464), p=0.000), probing depth (WMD = -4.545 (95% CI -5.621 – (-3.468), p=0.000), and bony defect depth (WMD = -4.020 (95% CI -4.873 – (-3.167), p=0.009). However, the data was high heterogeneity (I2=92.0%, I2=88.0%, and I2=74.0%).

Conclusion : The result evidences suggest that the novel cell sheet technique benefits on periodontal regeneration. However, as less clinical trials and possible the risk of bias problems, the further higher quality researches are still required to prove the effectiveness of cell sheet engineering for periodontal tissue regeneration in clinical applications in the future.


Download data is not yet available.


Pihlstrom BL, Michalowicz BS, Johnson NW. Periodontal diseases. Lancet 2005;366:1809-20.

Melcher AH. On the repair potential of periodontal tissues.J Periodontol 1976;47:256-60.

Bartold PM, Gronthos S, Ivanovski S, Fisher A, Hutmacher DW. Tissue engineered periodontal products. J Periodontal Res 2016;51:1-15.

Xu XY, Li X, Wang J, He XT, Sun HH, Chen FM. Concise Review:Periodontal Tissue Regeneration Using Stem Cells: Strategies and Translational Considerations. Stem Cells Transl Med 2019;8:392–403.

Han J, Menicanin D, Gronthos S, Bartold PM. Stem cells, tissue engineering and periodontal regeneration. Aust Dent J2014;59:117–30.

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

Bartold PM, McCulloch CA, Narayanan AS, Pitaru S. Tissue engineering: a new paradigm for periodontal regeneration based on molecular and cell biology. Periodontol 2000.2000; 24:253–69.

Lodi D, Iannitti T, Palmieri B. Stem cells in clinical practice:applications and warnings. J Exp Clin Cancer Res 2011; 30:9.

Chen FM, Shi S. Periodontal Tissue Engineering. Principles of Tissue Engineering; 2014.

Yamada N, Okano T, Sakai H, Karikusa F, Sawasaki Y, Sakurai Y. Thermo-responsive polymeric surfaces;control of attachment and detachment of cultured cells. Makromol Chem Rapid Commun 1990;11:571–6.

Okano T, Yamada N, Okuhara M, Sakai H, Sakurai Y. Mechanism of cell detachment from temperaturemodulated,hydrophilic-hydrophobic polymer surfaces.Biomaterials 1995;16:297–303.

Akizuki T, Oda S, Komaki M, Tsuchioka H, Kawakatsu N,Kikuchi A, et al. Application of periodontal ligament cell sheet for periodontal regeneration: a pilot study in beagle dogs. J Periodontal Res2005;40:245–51.

Hasegawa M, Yamato M, Kikuchi A, Okano T, Ishikawa I.Human periodontal ligament cell sheets can regenerate periodontal ligament tissue in an athymic rat model. Tissue Eng 2005;11:469–78.

Flores MG, Hasegawa M, Yamato M, Takagi R, Okano T,Ishikawa I. Cementum-periodontal ligament complexregeneration using the cell sheet technique. J Periodontal Res2008;43:364–71.

Tsumanuma Y, Iwata T, Washio K, Yoshida T, Yamada A,Takagi R, et al. Comparison of different tissue-derived stem cell sheets for periodontal regeneration in a canine 1-wall defect model. Biomaterials 2011;32:5819–25.

Gaubys A, Papeckys V, Pranskunas M. Use of Autologous Stem Cells for the Regeneration of Periodontal Defects in Animal Studies: a Systematic Review and Meta-Analysis. J Oral Maxillofac Res 2018;9:e3.

Yamamiya K, Okuda K, Kawase T, Hata KI, Wolff LF, Yoshie H. Tissue-engineered cultured periosteum used with platelet-rich plasma and hydroxyapatite in treating human osseous defects. J Periodontol 2008;79:811–8.

Feng F, Akiyama K, Liu Y, Yamaza T, Wang T-M, Chen JH, et al. Utility of PDL progenitors for in vivo tissue regeneration:a report of 3 cases. Oral Dis 2010;16:20–8.

Slim K, Nini E, Forestier D, Kwiatkowski F, Panis Y, Chipponi J. Methodological index for non-randomized studies (minors):development and validation of a new instrument. ANZ J Surg 2003;73:712–6.

Washio K, Iwata T, Mizutani M, Ando T, Yamato M, Okano T, et al. Assessment of cell sheets derived from human periodontal ligament cells: a pre-clinical study. Cell Tissue Res 2010;341:397–404.

Kobayashi J, Kikuchi A, Aoyagi T, Okano T. Cell sheet tissue engineering: Cell sheet preparation,harvesting/manipulation,and transplantation. J Biomed Mater Res A 2019;107:955–67.

Iwata T, Washio K, Yoshida T, Ishikawa I, Ando T, Yamato M, et al. Cell sheet engineering and its application for periodontal regeneration. J Tissue Eng Regen Med 2015;9:343–56.

Okuda K, Kawase T, Nagata M, Yamamiya K, Nakata K, Wolff LF, et al. Tissue-engineered cultured periosteum sheet application to treat infrabony defects: case series and 5-year results. Int J Periodontics Restorative Dent2013;33:281–7.

Okuda K, Yamamiya K, Kawase T, Mizuno H, Ueda M, Yoshie H. Treatment of human infrabony periodontal defects by grafting human cultured periosteum sheets combined with platelet-rich plasma and porous hydroxyapatite granules:case series. J Int Acad Periodontol 2009; 11:206–13.

Chen FM, Gao LN, Tian BM, Zhang XY, Zhang YJ, Dong GY,et al. Treatment of periodontal intrabony defects using autologous periodontal ligament stem cells: a randomized clinical trial. Stem Cell Res Ther 2016; 7:33.

Iwata T, Yamato M, Washio K, Yoshida T, Tsumanuma Y,Yamada A, et al. Periodontal regeneration with autologous periodontal ligament-derived cell sheets - A safety and efficacy study in ten patients. Regen Ther 2018;9:38–44.



How to Cite

Prateeptongkum เ. The Effect of Cell Sheet Engineering for Periodontal Tissue Regeneration in Clinical Studies: A Systematic Review and Meta-Analysis. j dept med ser [Internet]. 2021 Mar. 10 [cited 2022 Aug. 14];45(4):24-31. Available from:



Original Article

Most read articles by the same author(s)