Non-Cochrane · intervention · PM42783500
Cell-Based Therapies for Periodontal Regeneration: A Systematic Review and Meta-Analysis with Future Implications for Personalized Medicine.
Erazo Vaca Rafael X, Zambrano Manzaba Gabriela G, Bajaña Luis-Chauca, et al. · Journal of personalized medicine · 2026 · PubMed · doi:10.3390/jpm16090469
Findings
24 findings
| Population | ||||
|---|---|---|---|---|
| Patients with periodontal defects | Cell-based regenerative therapies, alone or with adjuncts | Conventional or cell-free periodontal regenerative therapies | Clinical attachment level gain | SMD 0.17 [-0.12, 0.45] Low Downgraded: risk of bias, imprecision 5 studies · 199 participants |
| Patients with periodontal defects (mainly intrabony defects associated with periodontitis) | Cell-based regenerative therapy (DPSCs, PDLSCs, BMSCs or cultured gingival fibroblasts, alone or with scaffolds/biomaterials) | Conventional or cell-free periodontal therapy (SRP with saline, cell-free scaffold/biomaterial, GTR + Bio-Oss, flap surgery) | Radiographic bone regeneration/bone fill One follow-up time point per study (minimum 3 months) · Clinical trials in China, Spain, Italy, Germany and Egypt · Sensitivity: leave-one-out, omitting Abdal-Wahab et al. 2020 | SMD 0.74 [-0.37, 1.84] GRADE not reported 3 studies |
| Patients with periodontal defects | Cell-based regenerative therapies, alone or with adjuncts | Conventional or cell-free periodontal regenerative therapies | Clinical attachment level gain Mean difference sensitivity analysis | MD 0.36 [-0.17, 0.9] GRADE not reported 5 studies |
| Patients with periodontal defects (mainly intrabony defects associated with periodontitis) | Cell-based regenerative therapy (DPSCs, PDLSCs, BMSCs or cultured gingival fibroblasts, alone or with scaffolds/biomaterials) | Conventional or cell-free periodontal therapy (SRP with saline, cell-free scaffold/biomaterial, GTR + Bio-Oss, flap surgery) | Radiographic bone regeneration/bone fill One follow-up time point per study (minimum 3 months) · Clinical trials in China, Spain, Italy, Germany and Egypt · Sensitivity: leave-one-out, omitting Chen et al. 2016 | SMD 1.71 [0.23, 3.19] GRADE not reported 3 studies |
| Patients with periodontal defects | Cell-based regenerative therapies, alone or with adjuncts | Conventional or cell-free periodontal regenerative therapies | Probing depth reduction | SMD 0.13 [-0.22, 0.48] Low Downgraded: risk of bias, imprecision 5 studies · 199 participants |
| Patients with periodontal defects (mainly intrabony defects associated with periodontitis) | Cell-based regenerative therapy (DPSCs, PDLSCs, BMSCs or cultured gingival fibroblasts, alone or with scaffolds/biomaterials) | Conventional or cell-free periodontal therapy (SRP with saline, cell-free scaffold/biomaterial, GTR + Bio-Oss, flap surgery) | Clinical attachment level (CAL) gain One follow-up time point per study (minimum 3 months) · Clinical trials in China, Spain, Italy, Germany and Egypt · Sensitivity: leave-one-out, omitting Chen et al. 2016 | SMD 0.24 [-0.08, 0.57] GRADE not reported 4 studies |
| Patients with periodontal defects (mainly intrabony defects associated with periodontitis) | Cell-based regenerative therapy (DPSCs, PDLSCs, BMSCs or cultured gingival fibroblasts, alone or with scaffolds/biomaterials) | Conventional or cell-free periodontal therapy (SRP with saline, cell-free scaffold/biomaterial, GTR + Bio-Oss, flap surgery) | Radiographic bone regeneration/bone fill One follow-up time point per study (minimum 3 months) · Clinical trials in China, Spain, Italy, Germany and Egypt · Sensitivity: leave-one-out, omitting Liu et al. 2025 | SMD 1.57 [-0.20, 3.35] GRADE not reported 3 studies |
| Patients with periodontal defects (mainly intrabony defects associated with periodontitis) | Cell-based regenerative therapy (DPSCs, PDLSCs, BMSCs or cultured gingival fibroblasts, alone or with scaffolds/biomaterials) | Conventional or cell-free periodontal therapy (SRP with saline, cell-free scaffold/biomaterial, GTR + Bio-Oss, flap surgery) | Clinical attachment level (CAL) gain One follow-up time point per study (minimum 3 months) · Clinical trials in China, Spain, Italy, Germany and Egypt · Sensitivity: leave-one-out, omitting Ferrarotti et al. 2018 | SMD 0.07 [-0.25, 0.38] GRADE not reported 4 studies |
| Patients with periodontal defects | Cell-based regenerative therapies, alone or with adjuncts | Conventional or cell-free periodontal regenerative therapies | Probing depth reduction Hartung–Knapp sensitivity analysis | SMD 0.13 [-0.42, 0.68] GRADE not reported 5 studies |
| Patients with periodontal defects (mainly intrabony defects associated with periodontitis) | Cell-based regenerative therapy (DPSCs, PDLSCs, BMSCs or cultured gingival fibroblasts, alone or with scaffolds/biomaterials) | Conventional or cell-free periodontal therapy (SRP with saline, cell-free scaffold/biomaterial, GTR + Bio-Oss, flap surgery) | Clinical attachment level (CAL) gain One follow-up time point per study (minimum 3 months) · Clinical trials in China, Spain, Italy, Germany and Egypt · Sensitivity: leave-one-out, omitting Liu et al. 2025 | SMD 0.20 [-0.26, 0.65] GRADE not reported 4 studies |
| Patients with periodontal defects | Cell-based regenerative therapies, alone or with adjuncts | Conventional or cell-free periodontal regenerative therapies | Radiographic bone regeneration Hartung–Knapp sensitivity analysis | SMD 1.27 [-0.94, 3.47] GRADE not reported 4 studies |
| Patients with periodontal defects (mainly intrabony defects associated with periodontitis) | Cell-based regenerative therapy (DPSCs, PDLSCs, BMSCs or cultured gingival fibroblasts, alone or with scaffolds/biomaterials) | Conventional or cell-free periodontal therapy (SRP with saline, cell-free scaffold/biomaterial, GTR + Bio-Oss, flap surgery) | Probing depth (PD) reduction One follow-up time point per study (minimum 3 months) · Clinical trials in China, Spain, Italy, Germany and Egypt · Sensitivity: leave-one-out, omitting Chen et al. 2016 | SMD 0.18 [-0.33, 0.69] GRADE not reported 4 studies |
| Patients with periodontal defects (mainly intrabony defects associated with periodontitis) | Cell-based regenerative therapy (DPSCs, PDLSCs, BMSCs or cultured gingival fibroblasts, alone or with scaffolds/biomaterials) | Conventional or cell-free periodontal therapy (SRP with saline, cell-free scaffold/biomaterial, GTR + Bio-Oss, flap surgery) | Probing depth (PD) reduction One follow-up time point per study (minimum 3 months) · Clinical trials in China, Spain, Italy, Germany and Egypt · Sensitivity: leave-one-out, omitting Apatzidou et al. 2021 | SMD 0.20 [-0.18, 0.59] GRADE not reported 4 studies |
| Patients with periodontal defects (mainly intrabony defects associated with periodontitis) | Cell-based regenerative therapy (DPSCs, PDLSCs, BMSCs or cultured gingival fibroblasts, alone or with scaffolds/biomaterials) | Conventional or cell-free periodontal therapy (SRP with saline, cell-free scaffold/biomaterial, GTR + Bio-Oss, flap surgery) | Radiographic bone regeneration/bone fill One follow-up time point per study (minimum 3 months) · Clinical trials in China, Spain, Italy, Germany and Egypt · Sensitivity: leave-one-out, omitting Ferrarotti et al. 2018 | SMD 1.06 [-0.72, 2.83] GRADE not reported 3 studies |
| Patients with periodontal defects (mainly intrabony defects associated with periodontitis) | Cell-based regenerative therapy (DPSCs, PDLSCs, BMSCs or cultured gingival fibroblasts, alone or with scaffolds/biomaterials) | Conventional or cell-free periodontal therapy (SRP with saline, cell-free scaffold/biomaterial, GTR + Bio-Oss, flap surgery) | Probing depth (PD) reduction One follow-up time point per study (minimum 3 months) · Clinical trials in China, Spain, Italy, Germany and Egypt · Sensitivity: leave-one-out, omitting Liu et al. 2025 | SMD 0.17 [-0.38, 0.72] GRADE not reported 4 studies |
| Patients with periodontal defects (mainly intrabony defects associated with periodontitis) | Cell-based regenerative therapy (DPSCs, PDLSCs, BMSCs or cultured gingival fibroblasts, alone or with scaffolds/biomaterials) | Conventional or cell-free periodontal therapy (SRP with saline, cell-free scaffold/biomaterial, GTR + Bio-Oss, flap surgery) | Probing depth (PD) reduction One follow-up time point per study (minimum 3 months) · Clinical trials in China, Spain, Italy, Germany and Egypt · Sensitivity: leave-one-out, omitting Ferrarotti et al. 2018 | SMD -0.02 [-0.33, 0.29] GRADE not reported 4 studies |
| Patients with periodontal defects | Cell-based regenerative therapies, alone or with adjuncts | Conventional or cell-free periodontal regenerative therapies | Probing depth reduction Low overall risk of bias | SMD 0.26 [-0.27, 0.78] GRADE not reported 3 studies |
| Patients with periodontal defects (mainly intrabony defects associated with periodontitis) | Cell-based regenerative therapy (DPSCs, PDLSCs, BMSCs or cultured gingival fibroblasts, alone or with scaffolds/biomaterials) | Conventional or cell-free periodontal therapy (SRP with saline, cell-free scaffold/biomaterial, GTR + Bio-Oss, flap surgery) | Clinical attachment level (CAL) gain One follow-up time point per study (minimum 3 months) · Clinical trials in China, Spain, Italy, Germany and Egypt · Sensitivity: leave-one-out, omitting Apatzidou et al. 2021 | SMD 0.20 [-0.10, 0.50] GRADE not reported 4 studies |
| Patients with periodontal defects (mainly intrabony defects associated with periodontitis) | Cell-based regenerative therapy (DPSCs, PDLSCs, BMSCs or cultured gingival fibroblasts, alone or with scaffolds/biomaterials) | Conventional or cell-free periodontal therapy (SRP with saline, cell-free scaffold/biomaterial, GTR + Bio-Oss, flap surgery) | Clinical attachment level (CAL) gain One follow-up time point per study (minimum 3 months) · Clinical trials in China, Spain, Italy, Germany and Egypt · Sensitivity: leave-one-out, omitting Sánchez et al. 2020 | SMD 0.14 [-0.16, 0.45] GRADE not reported 4 studies |
| Patients with periodontal defects | Cell-based regenerative therapies, alone or with adjuncts | Conventional or cell-free periodontal regenerative therapies | Radiographic bone regeneration | SMD 1.25 [-0.08, 2.58] Low Downgraded: imprecision, inconsistency 4 studies · 183 participants |
| Patients with periodontal defects | Cell-based regenerative therapies, alone or with adjuncts | Conventional or cell-free periodontal regenerative therapies | Probing depth reduction Mean difference sensitivity analysis | MD 0.27 [-0.52, 1.06] GRADE not reported 5 studies |
| Patients with periodontal defects (mainly intrabony defects associated with periodontitis) | Cell-based regenerative therapy (DPSCs, PDLSCs, BMSCs or cultured gingival fibroblasts, alone or with scaffolds/biomaterials) | Conventional or cell-free periodontal therapy (SRP with saline, cell-free scaffold/biomaterial, GTR + Bio-Oss, flap surgery) | Probing depth (PD) reduction One follow-up time point per study (minimum 3 months) · Clinical trials in China, Spain, Italy, Germany and Egypt · Sensitivity: leave-one-out, omitting Sánchez et al. 2020 | SMD 0.14 [-0.32, 0.60] GRADE not reported 4 studies |
| Patients with periodontal defects | Cell-based regenerative therapies, alone or with adjuncts | Conventional or cell-free periodontal regenerative therapies | Clinical attachment level gain Hartung–Knapp sensitivity analysis | SMD 0.17 [-0.23, 0.56] GRADE not reported 5 studies |
| Patients with periodontal defects | Cell-based regenerative therapies, alone or with adjuncts | Conventional or cell-free periodontal regenerative therapies | Clinical attachment level gain Low overall risk of bias | SMD 0.2 [-0.18, 0.57] GRADE not reported 3 studies |
Included primary studies 6
Open in Studies| Study | Year | Also included by | Outcomes it informs here | Trial data |
|---|---|---|---|---|
| Ferrarotti 2018 Human intrabony defect regeneration with micrografts containing dental pulp stem cells: A randomized controlled clinical trial. PMID:29779220 | 2018 | 4 other reviews | not stated | not extracted yet |
| Chen 2016 Treatment of periodontal intrabony defects using autologous periodontal ligament stem cells: a randomized clinical trial. PMID:26895633 | 2016 | 3 other reviews | not stated | not extracted yet |
| Sánchez 2020 Periodontal regeneration using a xenogeneic bone substitute seeded with autologous periodontal ligament-derived mesenchymal stem cells: A… PMID:32946590 | 2020 | 3 other reviews | not stated | not extracted yet |
| Apatzidou 2021 A tissue-engineered biocomplex for periodontal reconstruction. A proof-of-principle randomized clinical study. PMID:33899259 | 2021 | 2 other reviews | not stated | not extracted yet |
| Abdal-Wahab 2020 Regenerative potential of cultured gingival fibroblasts in treatment of periodontal intrabony defects (randomized clinical and biochemical… PMID:32080858 | 2020 | 1 other review | Radiographic bone regeneration | not extracted yet |
| Liu 2025 Impact of allogeneic dental pulp stem cell injection on tissue regeneration in periodontitis: a multicenter randomized clinical trial. PMID:40739139 | 2025 | 1 other review | not stated | not extracted yet |
Overlap with other reviews
Reviews that include the same primary studies are not independent evidence. Shared counts match studies by PMID, DOI or NCT, and otherwise by author and year (a probable match). Only the non-Cochrane dental reviews have study lists, so overlap with Cochrane reviews is not counted yet.
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Patients with periodontal defects, particularly intrabony defects associated with periodontitis | Patients with periodontitis and periodontal/intrabony defects (n=6 studies) |
| Intervention | Periodontal regenerative approaches with a viable cellular component (PDLSCs, BMSCs, DPSCs, ADSCs, GMSCs, cultured gingival fibroblast preparations), alone or with scaffolds, biomaterials or growth factors | DPSCs (n=2: Liu 2025 injectable allogeneic, Ferrarotti 2018 on collagen scaffold); autologous PDLSCs (n=2: Sanchez 2020 with collagen scaffold, Chen 2016 with GTR + Bio-Oss); BMSCs + scaffold (n=1: Apatzidou 2021); cultured gingival fibroblasts (n=1: Abdal-Wahab 2020) |
| Comparison | Conventional periodontal regenerative treatment (SRP, GTR, bone grafting, cell-free biomaterials) | Saline injection + SRP (n=1); cell-free collagen scaffold or conventional regenerative biomaterial (n=2); GTR + Bio-Oss (n=1); conventional flap surgery/scaffold without cells (n=1); conventional periodontal therapy (n=1) |
| Outcomes | Primary: CAL gain, PD reduction; secondary: radiographic bone fill, histological regeneration, safety outcomes | CAL gain (n=5); PD reduction (n=5); radiographic bone regeneration (n=4); safety (narrative only, n=6) |
| Study designs | Randomized and quasi-randomized controlled clinical trials | RCTs (n=5); quasi-randomized controlled trial (n=1) |
| Timing | Minimum follow-up 3 months; one time point per outcome per study | Not specified per study (12-month follow-up reported for Sanchez 2020 and Apatzidou 2021) |
AMSTAR 2 items
Two independent extractors rated each item. Their ratings are shown side by side because they have not been reconciled yet. The overall rating follows Shea et al. 2017: one critical flaw gives Low, more than one gives Critically Low.
| Item | Extractor A | Extractor B | Agree |
|---|---|---|---|
| 1Research question includes PICO components | Yes | Yes | yes |
| 2Protocol established before the reviewcritical | Partial Yes | Partial Yes | yes |
| 3Choice of study designs explained | No | Yes | no |
| 4Comprehensive literature searchcritical | Partial Yes | Partial Yes | yes |
| 5Study selection in duplicate | Yes | Yes | yes |
| 6Data extraction in duplicate | Yes | Yes | yes |
| 7List of excluded studies with reasonscritical | No | No | yes |
| 8Included studies described in detail | Partial Yes | Partial Yes | yes |
| 9Risk of bias assessed satisfactorilycritical | RCT: Yes · NRSI: Yes | RCT: Yes · NRSI: Yes | yes |
| 10Funding of included studies reported | No | No | yes |
| 11Appropriate meta-analysis methodscritical | RCT: Yes · NRSI: No | RCT: Yes · NRSI: No | yes |
| 12Impact of risk of bias on the pooled results | Yes | Yes | yes |
| 13Risk of bias accounted for in interpretationcritical | Yes | Yes | yes |
| 14Heterogeneity explained | Yes | Yes | yes |
| 15Publication bias investigatedcritical | Yes | No | no |
| 16Conflicts of interest reported | Yes | Yes | yes |
| Overall | Critically Low | Critically Low | yes |