Precise Adaptability and Bioactive Integration: A Two-Step Cross-Linked Hydrogel for Irregular Bone Defect Repair

Bone defect repair is a critical clinical orthopedic challenge, with existing materials suffering from insufficient bioactivity and poor bone-host integration. This study designed an injectable composite hydrogel (Ox-GAU-MgO) via dynamic covalent chemistry and photo-cross-linking synergy, using GelMA/AlgMA as the matrix and incorporating Ox-Dex and MgO NPs. Regulating Ox-Dex concentration enabled precise control of hydrogel modulus and viscosity. The material exhibited good injectability and biocompatibility, promoted BMSCs osteogenic differentiation and HUVECs migration in vitro, and significantly enhanced new bone formation and vascularization via "osteogenesis-angiogenesis coupling" in rat femoral condyle defects in vivo. Mechanistically, it activated JAK-STAT, HIF-1, and AMPK pathways to form a regulatory network. This work provides a novel strategy for bone defect repair materials, and the Ox-GAU-MgO hydrogel holds promising clinical potential with convenient operability and excellent osteogenic capacity.