3D-Printed hydroxysafflor yellow A/hydrogel porous scaffolds for bone regeneration.

The integration of angiogenesis with osteogenesis is crucial for the success of scaffolds in treating bone defects. Here, we present a strategy to address this challenge by engineering a 3D-printed porous scaffold that delivers hydroxysafflor yellow A (HSYA), a pro-angiogenic and osteogenic compound from traditional Chinese medicine, within a GelMA/HAMA hydrogel matrix. An optimized 8% GelMA/2% HAMA bioink provided excellent printability, fidelity, and porosity, enabling the fabrication of scaffolds with sustained HSYA release over four weeks. In vitro, the scaffold demonstrated excellent biocompatibility and concurrently enhanced the osteogenic differentiation of BMSCs and the angiogenic activity of HUVECs. In a rat cranial defect model, this dual bioactivity resulted in a bone volume fraction close to 35% at 8 weeks, accompanied by significantly improved local blood perfusion. By synergistically merging a traditional Chinese medicine-derived active molecule with advanced 3D printing technology, this study offers a promising strategy for vascularized bone regeneration.