Elevator-Like Hollow Channels in Porous Scaffolds Accelerate Vascularized Bone Regeneration via NETs-Fibrin-Mediated...

Developing viable tissue-engineered constructs for large-scale bone defects remains a fundamental challenge due to the difficulty of establishing adequate vascular networks. Channel structures act as biological elevators, rapidly promoting vascularization in scaffold materials. However, the underlying mechanisms driving this accelerated process remain unclear. In this study, porous silk fibroin (SF) scaffolds with hollow channels are engineered to investigate their vascularization-accelerating mechanisms. It is demonstrated that the channels enable the rapid infiltration of fibrinogen and platelets. This initiates a sequential biological cascade involving neutrophil recruitment, the formation of neutrophil extracellular traps (NETs), and subsequent macrophage migration. This coordinated process generates a provisional yet bioactive matrix that promotes directional vascular invasion. Leveraging the architecture of the hollow channels, a biomimetic system is developed that rapidly establishes provascular microenvironments featuring macrophage-populated NETs-fibrin networks through blood clot preloading. This combined structural and biological strategy enhances angiogenic-osteogenic coupling through spatially controlled bone morphogenetic protein-2 (BMP-2) presentation, significantly improving bone regeneration and providing a clinically translatable solution for vascularized bone regeneration. This study not only elucidates the mechanistic link between scaffold architecture and host immune response, but also establishes a novel paradigm for biomaterial design in hard tissue engineering.