Abstract
Bone vasculature plays a critical role in maintaining bone health. A reduction in mechanical loading-induced vascular deficiency plays a critical role in osteoporosis progression by disrupting the bone microenvironment and impairing intercellular communication among endothelial cells, osteoblasts, and osteoclasts. A bioactive nanoparticle, formed by fusing mechanically loading-induced preosteoclasts (POCs)-derived exosomes (ML-Exo) with (DSS)6 peptide-modified endothelial cell membrane vesicles (DMVs), reconstructs vascular networks and the bone microenvironment, reversing osteoporosis. Mechanical loading enhances communication capacity of ML-Exo, enabling mechanical signal transmission to endothelial cells and promoting angiogenesis-osteogenesis coupling. Additionally, the CXCR4 protein and (DSS)6 peptide on DMVs facilitate bone tissue localization (soil entry), while endothelial cell membrane homologous chemotaxis ensures precise targeting of bone vasculature (direct irrigation). This "Mechanical Energy-Charged Navigating Pump" (MLE/DMV), formed by fusion of ML-Exo and DMVs, restores the "natural vascular scaffold network," improving blood supply and nutrient delivery to the bone microenvironment. It also restores intercellular communication among endothelial cells, osteoblasts, and osteoclasts, slowing osteoporosis progression.