Osteogenic GelMA /Calcium Oligophosphate Composite Hydrogel for Bone Regeneration

ABSTRACT

Critical‐sized bone defects (CSDs) represent a major clinical challenge due to their limited self‐healing capacity. Conventional hydrogels incorporating crystalline hydroxyapatite (HA) often fail to recapitulate the hierarchical nanostructure of native bone, leading to suboptimal regeneration outcomes. To overcome this, we developed a biomimetic hydrogel by molecularly integrating amorphous calcium phosphate oligomers (CPO) into gelatin methacryloyl (GelMA), enabling a bone‐like organic–inorganic hybrid network. This composite exhibits outstanding performance: an ultimate strength of 192 kPa at 18 wt% CPO confirms robust mechanical reinforcement, while 54% mass retention after 56 days underscores exceptional degradation resistance and dose‐dependent bioactivity, evidenced by a two‐fold upregulation of alkaline phosphatase (ALP) activity. The amorphous CPO facilitates biomimetic HA nucleation within the GelMA matrix, mimicking the natural mineralization process. In a rat calvarial CSD model, the hydrogel promoted 60% bone volume regeneration within 12 weeks, significantly outperforming conventional composites, through seamless host integration, vascularized trabecular bone formation, and a collagen–mineral hierarchy resembling native osteogenesis. This study establishes CPO as a transformative component that converts passive scaffolds into bioactive osteogenic microenvironments, offering a clinically viable strategy for complex bone regeneration.