Sr²⁺-coordinated asiatic acid/silk fibroin hybrid hydrogels for enhanced osteogenesis and antibacterial therapy in infective bone defects.

Infectious bone defects (IBD), characterized by persistent bacterial infection and impaired bone regeneration, remain a major clinical challenge. Although numerous biomaterials have been developed, most fail to simultaneously achieve antibacterial efficacy and osteogenic promotion. Here, we innovatively designed a strontium ion (Sr²⁺)-coordinated asiatic acid/silk fibroin (AA-Sr/SF) composite hydrogel that synergistically integrates a natural bioactive compound, inorganic ions, and a protein matrix. This unique strategy endows the hydrogel with dual antibacterial and osteoinductive functions. Systematic characterization demonstrated its excellent mechanical stability, controlled degradability, and sustained release behavior. Functional assays revealed that AA-Sr/SF effectively inhibited Staphylococcus aureus while significantly enhancing osteoblast differentiation. In vivo, the hydrogel reduced bacterial burden in infected defects, facilitated new bone formation, and restored bone mass. Transcriptomic analysis further suggested that AA-Sr/SF promotes osteogenesis via activation of the BMP4-ID2/ID3 axis and calcium signaling pathway. Collectively, this study introduces a multifunctional hydrogel integrating antibacterial, osteogenic, and translational advantages, offering a promising material-based strategy for the precise treatment of infectious bone defects.