Resveratrol-Loaded Nanocarriers for Bone and Periodontal Regeneration: A Systematic Review

Introduction/Objective: Bone regeneration plays a critical role in the treatment of maxillofacial and musculoskeletal diseases by restoring lost or damaged bone tissue to support function and structural integrity. In this systematic review, we aimed to investigate the effects and mechanisms of Resveratrol (RSV) Nanoparticles (NPs) on bone regeneration in bone diseases and maxillofacial surgery. Methods: This study followed the PRISMA 2020 guidelines. A comprehensive search on PubMed/MEDLINE, Scopus, Web of Science (WOS), Embase, and the Cochrane Library was conducted for studies published before July 2, 2025. Data extraction was conducted for the included studies, and the results were reviewed. Results: RSV-NPs upregulated key osteogenic markers, including Runt-Related Transcription Factor 2 (Runx2), Alkaline Phosphatase (ALP), Osteocalcin (OCN), Osteopontin (OPN), Type I Collagen (Col-I), Bone Morphogenetic Protein-2 (BMP-2), and Insulin-Like Growth Factor-2 (IGF-2), and increased ALP activity, calcium deposition, and extracellular matrix mineralization. It promoted human bone marrow proliferation and induced osteoblast-like morphology. RSV-NPs reduced pro-inflammatory cytokines and Reactive Oxygen Species (ROS). Additionally, RSVNPs demonstrated anti-senescence and mitochondrial-protective effects. It also enhanced bone defect healing, increased Bone Volume Fraction (BV/TV) and Bone Mineral Density (BMD), promoted neovascularization, and synchronized scaffold degradation with new bone formation. Discussion: RSV-NPs enhance bone regeneration. These results align with previous evidence supporting nanoparticle-mediated drug delivery. However, limitations include a lack of standardized formulation techniques and limited clinical translation to date. Further research should prioritize toxicity profiling, scalability, and clinical trials. Conclusion: RSV-NPs show promise for bone regeneration, offering more effective, targeted treatment with reasonable safety and low cytotoxicity.