Bamboo-Like Whiskers-Reinforced Bioceramics Accelerate Large Segmental Bone Regeneration via Dual Modulation of Type-H Vessels and Osteoinduction.

Regenerative repair of segmental bone defect remains a major clinical challenge. The conventional mental implants suffer from mechanical strength mismatch and long-term foreign bodies presence. While, the osteoinductive materials lack insufficient mechanical strength for the repair of load-bearing bone. Inspired by bamboo, whisker-reinforced Ca-P ceramics (HW) have been developed to accelerate segmental bone regeneration. Bamboo-like whiskers can reduce the stress concentration and impede crack propagation via whisker broken, whisker bridging, and crack deflection, achieving 3 times increase in the compressive strength compared to traditional ceramics. In addition, HW significantly promotes the formation of type-H endothelial cells (ECs) via the integrin-mediated HIF-1 signaling pathway, which can secrete coupling factors (e.g. Noggin), to promote the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). In turn, HW can stimulate BMSCs to secrete coupling factors (e.g. VEGF) to support angiogenesis. In the segmental bone defect model, DFO is introduced to bamboo-like whiskers (HW+DFO) to enhance type-H vessels formation. HW+DFO can effectively promote the repair of segmental bone defects with mechanical recovery reaching 40% of that of normal femur. In conclusion, this study proposes a novel strategy for promoting bone regeneration by regulating type-H vessels, offering a potential solution for addressing segmental bone defects.