Bone matrix-mimetic DLP-printable gelatin and hyaluronic acid nanocomposite hydrogels for cranial defect repair

Cranial defect repair remains a major clinical challenge due to limited bone regenerative capacity and the need to preserve the adjacent neural microenvironment. Here, we developed a digital light processing printable biomimetic hydrogel scaffold based on gelatin methacrylate (GelMA), hyaluronic acid methacrylate (HAMA), and nano-hydroxyapatite (nHA), designed to recapitulate the organic-inorganic structure of native bone. The scaffold exhibited favorable printability, mechanical properties, and controlled swelling-degradation behavior. In vitro , it significantly enhanced cell proliferation and osteogenic differentiation. In a rat cranial defect model, the scaffold supported scaffold-associated tissue ingrowth, collagen-rich matrix remodeling, early vascularization, and apparent radiopaque defect filling, while showing acceptable compatibility with the adjacent cortical tissue. Transcriptomic and metabolomic analyses suggested coordinated changes in extracellular matrix (ECM) remodeling, angiogenesis, immune regulation, and metabolism-related remodeling. In addition, sustained release of Ca 2+ and phosphate ions may provide bioactive cues that support osteogenic differentiation and microenvironmental regulation. Overall, these findings indicate that the GelMA/HAMA/nHA scaffold may serve as a structurally supportive and bioactive platform for cranial defect repair.