Photocrosslinked organic-inorganic protein hydrogel with built-in nanoclusters for spatial biomineralization and enhanced osteogenesis

epairing complex bone defects (especially those associated with impaired mineralization) requires materials that combine structural support with controlled, spatial mineral formation. Inspired by nature’s biomineralization, we develop a biomimetic silk-based composite (BSC) hydrogel, which exhibits a “dynamic hardening” characteristic, achieved through phototriggered dual-crosslinking as well as Ca2+ coordination, enabling mineralization in vitro. The core of this strategy is an organic-inorganic hybrid network that integrates methacrylated silk fibroin (SilMA), a bifunctional phosphate crosslinker bis(2-methacryloyloxyethyl) phosphate (BMAP), and Ca2+. Photocuring yields a dual-crosslinked covalent‑coordinated network that stabilizes uniformly distributed amorphous calcium phosphate (ACP) nanoclusters and produces nanoscale channels throughout the matrix. Crucially, these embedded nanoclusters serve as nucleation sites, facilitating phase transformation into apatite‑like hydroxyapatite in simulated physiological conditions. This mineralization increased hydrogel stiffness (modulus from 0.033 MPa to 1.075 MPa) and generated a uniformly mineralized matrix within 7 days. The BSC formulation is compatible with digital light processing (DLP) and extrusion 3D printing and supports fabrication of anatomically relevant constructs. In a rat critical-sized calvarial defect model, BSC hydrogels promoted a pro-healing immune microenvironment, enhanced vascularization, and improved bone regeneration relative to controls. Overall, BSC hydrogels provide a bioinspired, print-friendly platform for the repair of challenging bone defects.