Strontium-Functionalized Biomaterials for Bone Regeneration: Mechanisms, Biological Functions, and Clinical Translational Progress.

Strontium (Sr), a trace element with osteogenic, anti-resorptive, immunomodulatory, angiogenic, and antibacterial activities, has become an important functional component in biomaterials for bone regeneration. This review systematically summarizes Sr-functionalized biomaterials, with emphasis on Sr2⁺-mediated molecular mechanisms, concentration-dependent bioactivity, local delivery strategies, fabrication-dependent ion-release behavior, antimicrobial and antioxidant functions, and clinical translational potential. Particular attention is given to the physicochemical regulation of Sr incorporation, therapeutic-ion synergy, fabrication-related release characteristics, and key challenges affecting translational application. In addition, we discuss how Sr cooperates with other therapeutic ions, including Mg, Zn, Cu, Se, and Ga, to coordinate osteogenesis, angiogenesis, immunomodulation, and infection control within the bone-regeneration microenvironment. Current limitations include the lack of unified optimal Sr dosing across different material platforms, insufficient long-term release and biosafety data, limited large-animal and clinical evidence, and an incomplete understanding of Sr-associated antimicrobial mechanisms. Overall, this review provides mechanistic insights and practical guidance for the rational design of next-generation Sr-functionalized bone-repair biomaterials.