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 Sr 2 ⁺-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. The infographic outlines Sr²⁺ benefits across fields. In osteogenesis, it aids bone formation and cell differentiation. For angiogenesis, it enhances bone regeneration via VEGF and HIF-1α. Its antimicrobial effects reduce bacterial adhesion and biofilm formation, while increasing membrane disruption and ROS. Immune modulation includes macrophage M2 polarization and cytokine regulation, improving osteoimmune conditions. As an antioxidant, Sr²⁺ lowers ROS, oxidative stress, lipid peroxidation and DNA damage, restoring redox balance. Clinical uses include Sr-doped scaffolds, hydrogels, implant coatings and bone cements, enhancing biocompatibility. It works with ions like Mg²⁺, Zn²⁺, Cu²⁺, Se²⁻ and Ga³⁺. Sr²⁺ shows potential in treating osteoporosis, repairing bone defects, enhancing implants, regenerating infected tissues and personalizing tissue engineering.Sr² benefits: bone growth, blood vessels, antimicrobial, immune boost, antioxidant, biomaterials.