Table 1.
In vivo studies employed orthotopic models to assess the regenerative capacity of cell sheet transplantation in periodontal defect models, with or without biomaterials.
| Author | Cells | Experimental Groups | Additional Pretreatment | Material | Technique | Experimental Setup | Results |
|---|---|---|---|---|---|---|---|
| Nakajima et al., 2008 [99] | HGFs | FN-ALP sheet group, FN sheet group, control (no treatment in the defect), control (without immunosuppressant FK administration) | None | None | FN matrix-based multilayered cell sheets of hGFs modified to express ALP (FN-ALP) | Orthotopic model of fenestration bone defects in rats |
FN- ALP-expressing hGFs supported the regeneration of cementum-like, PDL-like and bone tissue, exhibiting superior regenerative potential. |
| Ding et al., 2010 [100] | minipig PDLSCs | Control group, HA/TCP group, HA/TCP scaffolds +autologous pPDLSCs group, HA/TCP scaffolds + allogeneic Guizhou minipig pPDLSCs group, HA/TCP scaffolds+ autologous heterogenic minipig pPDLCs group |
None | HA/TCP | Cell sheet | Orthotopic model of experimental periodontitis in minipigs | Treatment containing either autologous or allogeneic pPDLSCs resulted in PDL-like tissue regeneration. The use of allogeneic cells did not result in immunological rejection. |
| Tsumanuma et al., 2011 [101] | Canine PDLSCs, BMMSCS, and APCs |
Control, PDLC group, BMMSC group, APC group |
None | Woven PGA, porous β-TCP and 3% type I collagen |
Three-layered cell sheets attached with PGA | One-wall defects were surgically created in dog |
The PDLC group exhibited enhanced cementum-like and PDL-like tissue regeneration, exhibiting more dense collagen fibers and thicker mineralized tissue. |
| Wei et al., 2012 [75] | PDLSCs | Vc-induced autologous PDLSCs sheet group, UpCell dish PDLSCs sheet group, Gelfoam scaffolds/dissociated autologous PDLSCs group (control) |
Vc treatment | Gelfoam scaffold | Cell sheet | Ectopic transplantation in nude mice, and orthotopic transplantation experimental periodontal lesions bone defect in miniature swines | Vc-induced PDLSCs sheet group and UpCell dish PDLSC sheet group application resulted in significantly more bone/cementum-like tissue formation compared to control/Vc-induced PDLSCs sheet group was significantly better. |
| Zhao et al., 2013 [102] | PDLSCs | PDLSCs/PRF construct group, cell sheet fragments group, PRF granules group | None | PRF granules | Combination of fragments from PDLSCs cell sheet and PRF granules | PDLSCs/PRF granules construct in tooth reimplantation in dogs | PDLSCs/PRF construct promoted PDL-like tissue regeneration and exhibited reduction in terms of inflammation and ankylosis. |
| Iwasaki et al., 2014 [103] | PDLSCs | Amnion group, PDLSC-amnion group | None | Decellularized amniotic membrane (amnion) | None | Application of PDLSCs -amnion in a periodontal defect model in rat maxillary molars | Histological and radiographic analysis showed that PDLSC-amnion group promoted PDL-like tissue regeneration. |
| Guo et al., 2014 [86] | Rat PDLSCs | MCPs group, MUCPs group, MCPs/TDM group, MUCPs/TDM group | None | TDM | MCP and MUCPs produced by MCS and MUCS | In vivo transplantation of MCPs or MUCPs into the imental pouch; periodontal defect model and in vivo transplantation of MCPs and MUCPs in rats |
All groups promoted cementum-like and PDL-like tissue regeneration, but MUCPs group exhibited superior behavior in terms of mineralization and collagen fiber arrangement compared to MCPs group. |
| Cao et al., 2015 [104] | hDPSCs | Control group, hDPSC injection group, HGF-hDPSC injection group, hDPSC sheet, HGFhDPSC sheets |
Adenovirus-mediated transfer of HGF gene to DPSCs |
None | Cell sheet of adenovirus-mediated transfer of HGF | 40 periodontitis lesions, three-wall intrabony defects, in the 1st molars of miniature pigs |
HGFhDPSC sheet group was able to promote PDL-like tissue formation and alveolar bone regeneration similar to that of native tissue, whereas the other groups provided only limited regeneration. |
| Hu et al., 2016 [105] | hDPSCs | Control group, hDPSC injection group, hDPSC sheep group | None | None | Cell injection or cell sheet transplantation |
Three-wall intrabony periodontal defects, in miniature pigs | Both experimental groups effectively promoted periodontal regeneration compared to control. hDPSC sheet application resulted in significantly better bone regeneration compared to the hDPSC injection. |
| Tsumanuma et al., 2016 [106] | Canine PDLSCs | Control group, autologous group, allogeneic group | None | Woven PGA, porous β-TCP and 3% type I collagen |
Three-layered cell sheets attached with PGA | Critical size supraalveolar periodontal defect model in dog |
Both autologous and allogeneic groups were able to regenerate bone, cementum-like and PDL-like tissue. |
| Yu et al., 2016 [90] | PDLSCs | Inflammation group, hypoxia group, inflammatory plus hypoxic stimuli-dual-stimuli group, no-stimulus group, blank group, CBB group |
Inflammatory conditions (inflammation), hypoxic conditions (hypoxia), or a combination of both (dual stimuli) conditions |
CBB | Cell sheet | Ectopic trasplantation model (subcutaneously) into the dorsal region, and orthotopic model with surgical creation of periodontal defects (3 mm × 1.5 mm) in nude mice | Hypoxia group exhibited more bone formation compared to other groups, while cementum-like and PDL-like tissue formation was identified in the no-stimulus and hypoxia groups. |
| Guo et al., 2017 [107] | PDLCs and DFCs | Control group, DFC sheet group, PDLC sheet group |
P. gingivalis LPS-induced inflammation microenvironment |
None | Cell sheet | Canine periodontitis model (two wall intrabony defects), in dogs | DFC sheet application was more effective in terms of bone, cementum-like and PDL-like tissue regeneration compared to the PDLC sheet. |
| Takewaki et al., 2017 [108] | BMMSCs | No graft, C-MSC in growth medium, C-MSC in OIM | Osteoinductive medium (OIM) | None | MSC/ECM complex (C-MSC) | Orthotopic model of class III furcation defect, in beagle dogs | Both C-MSC and C-MSC-OIM exhibited formation of cementum-like, PDL-like and bone formation leading to the regeneration of the periodontal complex. |
| Farag et al., 2018 [109] | PDLCs | Scaffold group, decellularized cell sheet/scaffold group | None | PCL | Decellularized cell sheet | Rat periodontal defect model in the mandible (orthotopic) | PDL-like tissue regeneration was observed in both groups. However, the group with the decellularized cell sheet presented higher detection of PDL fiber attachment with perpendicular orientation. |
| Iwata et al., 2018 [8] | PDLCs | PDL cell sheet group | None | β-TCP granules | cell sheet | Bony defects were filled with three-layered PDL-derived cell sheets and with β-TCP granules (clinical study) | Improvement was observed in terms of bone regeneration and clinical attachment 6 months after application of PDL-cell sheet. |
| Yanget al., 2019 [94] | DFCs and SHEDs | SHEDSs combined with TDM group, DFCSs combined with TDM group, TDM group | None | TDM | Cell sheet | Subcutaneous transplantation into nude mice and orthotopic implantation in Sprague-Dawley rats’ jawbone |
Both SHEDs/TDM and DFCs/TDM groups formed PDL-like tissues, enriched in collagen fibers and fibroblasts, with arrangement similar to that of native PDL. |
| Vaquette et al., 2019 [110] | GC, BMMSCs, and PDLCs | Control group (no cells on scaffold), GC group, BMMSC group, and PDLC group | None | PCL | Biphasic PCL scaffold consisting of bone and PDL compartments combined with the cell sheets. |
Dehiscence periodontal defects in sheep |
Bone, cementum-like and PDL-like tissue regeneration was observed in the BMMSC and PDLC groups compared to the GC and control group. |
| Yang et al., 2019 [111] | hDFCs | Blank group, cDFCSs group, TDMP group, HA/-TCPgroup, TDMP + cDFCSs group, HA/-TCP + cDFCSs group | None | TDM particles or HA/-TCP | Cell sheet | One-wall periodontal intrabony defects in beagle dogs | The use of materials enhanced bone formation. The presence of DFCs promoted the regeneration of bone and PDL-like tissue. |
| Raju et al., 2020 [97] | Rat PDL cells and osteoblastic cells | PDL cell sheet group, MC3T3-E1 cell sheet group, complex cell sheet group (containing both cells) | None | None | Cell sheet | Ectopic and orthotopic transplantation in vivo in mice | Ectopic transplantation of complex cell sheet resulted in PDL-like and bone tissue formation. Only complex cell sheet group was able to regenerate bone and PDL-like tissue similar to the native PDL-bone complex. |
| Jiang et al., 2021 [112] | hPDLCs | dHPDLC group, dHPDLC sheets loaded with PCL/GE group (dHPDLC-PCL/GE), control group |
None | PCL/GE nanofibers and 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) nanoparticles | Decellularized cell sheet | Periodontal defects (periodontal fenestration defect) in rats |
dHPDLC and dHPDLC-PCL/GE groups promoted new bone formation as well as PDL-like and cementum-like tissue regeneration compared to control. dHPDLC-PCL/GE group exhibited irregular and perpendicular fiber orientation in the regenerated PDL-like tissue. |