Abstract
Background: Resveratrol (RSV) is a polyphenolic compound with antioxidant, anti-inflammatory, osteomodulatory, and antimicrobial properties that may influence dental implant osseointegration and peri-implant tissue healing. However, preclinical findings remain inconsistent. This systematic review evaluated preclinical evidence on the effects of RSV on dental implant osseointegration and peri-implant tissue responses, with emphasis on pathological conditions, implant-surface modifications, delivery systems, and biological mechanisms. Methods: PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar were searched from inception to August 2026. In vivo and in vitro studies investigating RSV in dental implant, osseointegration, or implant-associated infection models were eligible. Outcomes included implant stability, bone-to-implant contact, peri-implant bone formation, osteogenic/osteoclast markers, inflammatory/oxidative responses, and antimicrobial activity. Risk of bias was assessed using SYRCLE for animal studies. Findings were synthesized narratively due to substantial heterogeneity. Results: Twenty studies were included. Systemic RSV showed beneficial effects in several experimental models of diabetes, smoking exposure, and aging/alcohol-associated skeletal impairment, whereas findings were inconsistent across streptozotocin-induced diabetes, type 2 diabetes models, and osteoporosis models. RSV-functionalized surfaces, hydrogels, membranes, nanotube coatings, and nanocomposite systems showed osteogenic, antioxidant, anti-inflammatory, immunomodulatory, and/or antimicrobial effects in experimental models. Antibacterial and antibiofilm effects were also reported. Proposed mechanisms involved modulation of ROS, NF-κB/MAPK signaling, osteogenesis, osteoclast activity, and macrophage polarization. Conclusions: RSV shows promise as a multifunctional adjunct for implant-associated bone healing and peri-implant tissue modulation. However, substantial heterogeneity and inconsistent findings limit definitive conclusions and warrant standardized, clinically relevant in vivo studies. These findings remain preclinical and should not be interpreted as evidence of clinical efficacy.