Clinical Outcomes of Periodontal Regeneration Using Biologic Agents Alone or in Combination with Graft Materials for Intrabony Defects: A Systematic Review and Meta-Analysis

Objectives: This systematic review with meta-analysis investigated whether combining bone grafts with biologic agents enhances clinical outcomes compared to biologic agents alone in the regenerative treatment of periodontal intrabony defects. Data sources: Electronic searches were conducted in PubMed, Web of Science, and Scopus up to December 18, 2024, following PRISMA guidelines. Manual screening of major periodontal journals complemented the search. Study selection: Randomized controlled trials with ≥6 months follow-up were included if they compared biologic agents alone (e.g., enamel matrix derivative, platelet-rich fibrin, recombinant growth factors) to their combination with bone grafts in the treatment of intrabony defects. Primary outcomes were probing pocket depth (PPD) reduction, clinical attachment level (CAL) gain, and radiographic bone level (RBL) gain. Results: Twenty-one RCTs (739 patients, 828 defects) met inclusion criteria. Combination therapy resulted in significantly greater PPD reduction (mean difference: 0.38 mm; p = 0.02) and RBL gain (0.81 mm; p = 0.003). CAL gain showed a favorable but non-significant trend (0.30 mm; p = 0.22). Gingival recession was slightly lower in the graft group, while BoP and PI were unaffected. Subgroup analyses suggested that PRF and growth factors derive more benefit from grafting, whereas enamel matrix derivatives (EMD) offered comparable outcomes with or without grafts. Conclusions: Limited yet measurable improvements in regenerative outcomes are obtained with the addition of graft materials to PRF and growth factors, while EMD seems to yield comparable outcomes regardless of grafting. Clinical relevance: These findings suggest that while grafting can enhance certain clinical parameters, its added value may depend on the specific biologic agent used, supporting a selective rather than systematic use in periodontal regenerative procedures.