Stem Cell-Based Therapies in Periodontology and Implant Dentistry: A Systematic Review and Meta-Analysis

Abstract

Introduction: Periodontal disease and peri-implantitis remain the leading causes of tooth and implant loss, and conventional regenerative procedures consistently fall short of full structural restoration. Stem cell therapies have emerged as a promising alternative, operating through multi-lineage differentiation, immunomodulation via paracrine signaling, and extracellular vesicle communication. Prior systematic reviews, however, lacked methodological rigor — omitting clustering adjustments, REML/HKSJ estimation, prediction intervals, and publication bias modeling. Aim: This systematic review and meta-analysis evaluated whether stem cell therapy produces superior clinical and radiographic outcomes compared to cell-free controls in adults with periodontal or peri-implant bone defects. Methods: Searches across PubMed/MEDLINE, Scopus, Embase, and Web of Science (through December 31, 2025) identified 45 eligible studies — 26 RCTs, 12 controlled animal studies, and 7 cohort studies — encompassing 1,891 human participants, with 28 contributing quantitative data. Results: REML/HKSJ pooling demonstrated significantly greater CAL gains (MD: 1.52 mm; 95% CI: 0.87–2.17 mm) and PD reductions (MD: −1.38 mm; 95% CI: −1.95 to −0.81 mm). A parity-restricted sensitivity analysis across 14 cell-only–differing studies confirmed an independent cellular contribution (CAL MD: 1.29 mm), robust across all intrasubject correlation assumptions. After Vevea-Hedges publication bias correction, the CAL effect attenuated to 1.19 mm —remaining clinically meaningful. Human bone-to-implant contact improved by +9.8% (PI: 1.3–18.3%), with animal models yielding +12.15%.GRADE certainty was moderate for CAL and PD outcomes, and low for radiographic measures and safety — attributed to limited follow-up and sparse adverse event reporting, with only one event recorded among 1,891 participants. Conclusion: Stem cell therapy demonstrates statistically significant and methodologically robust regenerative benefits. Widespread clinical adoption, however, awaits longer, well-powered RCTs with standardized cell potency reporting and prospective health-economic evaluation.