Potential of chrysin for osteogenesis and bone regeneration: a systematic review of preclinical evidence on free chrysin, regenerative systems, concentration responses, mechanisms, and craniofacial relevance

Chrysin (5,7-dihydroxyflavone) has shown osteogenic, antioxidant, and anti-inflammatory activities, but evidence on its osteogenic effects, concentration-response patterns, delivery systems, cytotoxicity, and mechanisms remains fragmented. This systematic review aimed to evaluate the effects of chrysin on osteogenic differentiation and bone regeneration and to characterize concentration-related responses, safety, delivery approaches, and mechanisms. This systematic review was conducted and reported in accordance with PRISMA 2020. Scopus, PubMed/MEDLINE, Web of Science, and Dentistry & Oral Sciences Source via EBSCOhost were searched from inception to 26 April 2026. Eligible studies reported osteogenic differentiation or bone-regeneration outcomes following chrysin-based interventions. Risk of bias was assessed using adapted OHAT and SYRCLE tools. Owing to substantial methodological heterogeneity, the findings were synthesized narratively. Eight studies were included; seven contained in vitro components and three contained animal components. In vitro evidence involved both free and formulated chrysin. The most responsive tested concentrations of free chrysin were 0.01–25 µM across different cell models, while formulated interventions used different nominal concentrations or loading levels. Most studies reported increased osteogenic differentiation, marker expression, or mineralization. None of the animal studies evaluated free chrysin as a standalone intervention; chrysin was assessed within regenerative systems involving pretreated cells, combined DBM/BMSC treatment, or scaffolds. Two animal studies reported improved bone-related outcomes, whereas one showed no significant regenerative benefit. Free chrysin showed osteogenic activity in vitro, while animal studies evaluated chrysin only within regenerative systems. The most responsive tested concentrations varied across biological models and formulations, and the independent in vivo effect of free chrysin remains undetermined. PROSPERO CRD420261332524.