The hypoxic and hypobaric conditions of high-altitude environments significantly impair osteogenesis and angiogenesis, leading to delayed bone healing and posing clinical challenges. In this study, we developed Yoda1-loaded chitosan sustained-release microspheres (Yoda1@CSM) to locally deliver the Piezo1 agonist Yoda1 and enhance bone regeneration under simulated high-altitude conditions. The microspheres were fabricated using a water-in-oil-in-water (W/O/W) double emulsion method. Their biological effects were assessed in vitro using bone marrow mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) under normoxic and hypoxic conditions. Results demonstrated that Yoda1@CSM significantly enhanced alkaline phosphatase (ALP) activity and upregulated osteogenic markers (ALP, BMP-2, RUNX2) in BMSCs, while also promoting tube formation and VEGF secretion in HUVECs. These findings indicate that Yoda1@CSM effectively stimulates osteogenesis and angiogenesis in hypoxic environments and holds promising potential for the treatment of bone defects at high altitude.
Ouyang et al. (Sun,) studied this question.