A moldable hydrogel based on sericin and Zn2+/F- dual-doped hydroxyapatite promotes skull defect repair through the synergistic effects of immunoregulation, enhanced angiogenesis and osteogenesis

Skull defect repair typically involves multiple stages, including immunomodulation, angiogenesis, osteogenic differentiation, and biomineralization, etc. Most existing therapeutic biomaterials fail to show functional effects across all these stages, leading to unsatisfactory repair effects. To address this challenge, an organic–inorganic hybrid HT(SA)HAp moldable hydrogel with the aforementioned functional properties was developed. The moldable hydrogel consisted of phenylboronic acid-grafted hyaluronic acid, tannic acid, alendronate sodium-grafted sericin (Ser-AL), and hydroxyapatite co-doped with 5 % Zn and 10 % F (Zn5%/F10%-HAp). These materials were cross-linked due to phenylborate ester bonds, metal-phenol interactions, and the AL-mediated chelation of divalent metal cations. Sericin-mediated immunomodulation serves as a precursor to micro-environmental regulation, reducing inflammation at the site of injury and creating an environment conducive to angiogenesis and osteogenic differentiation. The degradation products of the hydrogel's organic skeleton promoted the proliferation of mesenchymal stem cells and vascular endothelial cells. The enhanced paracrine effect of mesenchymal stem cells and the release of Zn2+ from modified Zn5%/F10%-HAp promoted angiogenesis, while the degradation products of these materials ensured continued promotion of osteogenic differentiation and biomineralization. This organic–inorganic hybrid hydrogel had the synergistic effects of immunoregulation, enhanced angiogenesis, osteogenic differentiation, and biomineralization, which could significantly accelerate the repair of skull defects, and demonstrate completely repaired skull defects at 8 weeks. Thus, this multifunctional moldable hydrogel provided an effective and stable treatment strategy for the rapid repair of skull defects.