Enhancing Bone Regeneration: The Role of Biomimetic Silicified Collagen Scaffold in Osteogenesis and Angiogenesis

ABSTRACT The identification of materials that effectively promote mineralization and vascularization is crucial for advancing clinical applications in bone regeneration. Biomimetic silicified collagen scaffold (SCS) has emerged as a promising candidate, demonstrating significant potential to enhance both osteogenesis and angiogenesis. However, the mechanisms by which SCS directly influences angiogenesis to facilitate bone defect healing remain largely unexplored. In this study, we observed that the implantation of SCS in rabbit femoral defects resulted in extensive bone regeneration and angiogenesis at the wound sites. Notably, SCS outperformed commercial alternatives such as Bio‐Oss in terms of degradation and angiogenic response. In vitro assays further demonstrated that SCS upregulates angiogenic protein expression and promotes endothelial cell angiogenesis through the activation of the HIF‐1α/VEGF signaling pathway. Consequently, SCS modulates the phenotype of vascular endothelial cells, leading to the formation of CD31 hi Emcn hi type H endothelial cells, which are critical for effective bone regeneration. This study offers valuable perspectives on the dual effects of silicified materials on osteogenesis and angiogenesis, advancing the understanding of their potential functions in regenerative medicine.