Synergistic 3D-bioprinted scaffold with multi-level adaptability for vascularized bone regeneration via osteogenesis-angiogenesis coupling.

3D bioprinting enables the fabrication of biomimetic, cell-laden and pro-osteogenic constructs with high precision for bone regeneration. The ability of integrating favorable mechanical strength and multi-material interactive bioactivity in engineered constructs for efficient bone defect repair is still a challenge. Herein, we employed a dual-nozzle synergistic 3D bioprinting technology to fabricate a biocomposite scaffold that integrated interactive soft hydrogel filaments and hard polycaprolactone (PCL)-based filaments by mimicking weave patterns. The multi-material scaffold design aimed at providing features of suitable microstructure and long-term mechanical support, enhanced vascularized bone regeneration for bone repair. Chitosan/hyaluronic acid functionalized mesoporous silica nanoparticles bearing osteogenic protein on the surface and angiogenic drug in the pores were embedded into cell-supportive hydrogel bioink for promoting osteogenesis-angiogenesis coupling. Meanwhile, MgO nanoparticles were incorporated into structure-supportive PCL matrix for improving mechanical strength and compensating angiogenic/osteogenic activities by sustained release of Mg