Synergistically reinforced bioresorbable hydrogel for mechanical-biological decoupling and osteogenic-angiogenic...

Ideal hydrogels for craniofacial bone regeneration should combine mechanical robustness, tunable bioresorption, and synergistic osteogenic-angiogenic bioactivity. However, conventional hydrogels suffer from an inherent trade-off between mechanical performance and biological activity, since both properties are dominated by crosslinking density. Here, a synergistically reinforced bioresorbable hydrogel system is developed by integrating highly ordered melt electrowriting poly(lactic-co-glycolic acid) (PLGA) microfibrous scaffolds with bioactive glass (BG)-reinforced and functionalized gelatin methacryloyl (GelMA) matrix. This architectural reinforcement provides a strategy for partial mechanical-biological decoupling, enabling mechanical properties to be tailored independently of hydrogel crosslinking while preserving the bioactivity of the GelMA phase. The composite hydrogel efficiently promotes osteogenic differentiation of rat bone marrow mesenchymal stem cells and enhances angiogenic activities of human umbilical vein endothelial cells. The enrichment of Ras/MAPK signaling suggests a potential bifunctional role of this pathway in osteogenic and angiogenic regulation. In a rat critical-sized calvarial defect model, the scaffold remarkably induces extensive vascularized bone regeneration, achieving a bone volume fraction of 59.9 ± 7.4% at 12 weeks post-implantation. This work establishes a synergistic reinforcement strategy that decouples mechanical and biological functions while orchestrating osteogenic-angiogenic coupling for craniofacial bone regeneration.