Scaffold-Based Biomaterials for Periodontal Regeneration in Periodontitis: A Systematic Review and Meta-Analysis

Background: Periodontitis is characterized by loss of the periodontal ligament, cementum, and alveolar bone. Scaffold-based biomaterials are intended to provide a three-dimensional framework for periodontal wound stabilization and tissue regeneration, but their incremental clinical benefit over conventional regenerative therapy remains uncertain. This systematic review and meta-analysis evaluated scaffold-based periodontal regenerative procedures for probing depth (PD) reduction, clinical attachment level (CAL) gain, and radiographic defect fill compared with conventional treatment. Methods: Original randomized controlled trials published from January 2020 to 1 March 2026 were searched in MEDLINE (Ovid), Embase, CENTRAL, and Web of Science, screened in Rayyan, and meta-analyzed in RevMan v5.4. Certainty was evaluated using GRADE. Results: Thirty-one studies were included. Scaffold-based interventions produced statistically significant but clinically modest PD reductions at 6 months (MD = −0.27 mm; 95% CI: −0.43 to −0.10; p = 0.001; I2 = 34%) and 12 months (MD = −0.21 mm; 95% CI: −0.41 to −0.01; p = 0.04; I2 = 22%), but not at 24 months. The overall PD effect was small (MD = −0.26 mm; p < 0.0001). CAL gain was not significant at 6 or 12 months but was significant at 24 months (MD = 1.00 mm; p < 0.0001; I2 = 0%). Defect fill improved at 12 months (MD = 0.51 mm; p = 0.02) but not at 6 months. Subgroup and meta-regression analyses did not identify significant effects of scaffold type or PRF/PRP enrichment (p > 0.05). Conclusions: Scaffold-based biomaterials may provide limited, time-dependent clinical and radiographic benefits as adjuncts to conventional periodontal regenerative therapy. The evidence remains constrained by heterogeneous interventions, modest effect sizes, low-to-very-low certainty for several outcomes, and a paucity of histologic confirmation of true periodontal regeneration.