Accelerated Bone Reconstruction by the Yoda1 Bilayer Membrane via Promotion of Osteointegration and Angiogenesis

Abstract Guided bone regeneration membranes are widely used to prevent fibroblast penetration and facilitate bone defect repair by osteoblasts. However, the current clinically available collagen membranes lack bone induction and angiogenic capacities, exhibiting limited bone regeneration. The mechanically sensitive channel, Piezo1, which is activated by Yoda1, has been reported to play crucial roles in osteogenesis and angiogenesis. Nevertheless, the application of Yoda1 alone is unsustainable to maintain this activity. Therefore, this study fabricates a Yoda1‐loading bilayer membrane using electrospinning technology. Its inner layer in contact with the bone defect is composed of vertically aligned fibers, which regulate the proliferation and differentiation of cells, release Yoda1, and promote bone regeneration. Its outer layer in contact with the soft tissue is dense with oriented fibers by UV cross‐linking, mainly preventing fibroblast infiltration and inhibiting the immune response. Furthermore, the loaded Yoda1 affects osteogenesis and angiogenesis via the Piezo1 / RhoA /Rho‐associated coiled‐coil‐containing protein kinase 1/Yes1‐associated transcriptional regulator signaling pathway. The results reveal that the Yoda1 bilayer membrane is efficient and versatile in accelerating bone regeneration, suggesting its potential as a novel therapeutic agent for various clinical issues.