Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, 510055, China.
Adv Healthc Mater. 2023 Jul;12(18):e2203105. doi: 10.1002/adhm.202203105. Epub 2023 Mar 21.
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.
引导骨再生膜被广泛用于防止成纤维细胞渗透，并通过成骨细胞促进骨缺损修复。然而，目前临床可用的胶原膜缺乏成骨和血管生成能力，骨再生能力有限。机械敏感通道 Piezo1 被 Yoda1 激活，已被报道在成骨和血管生成中发挥关键作用。然而，单独使用 Yoda1 来维持这种活性是不可持续的。因此，本研究使用静电纺丝技术制备了一种装载 Yoda1 的双层膜。与骨缺损接触的内层由垂直排列的纤维组成，调节细胞的增殖和分化，释放 Yoda1，并促进骨再生。与软组织接触的外层通过 UV 交联形成密集的定向纤维，主要防止成纤维细胞渗透和抑制免疫反应。此外，负载的 Yoda1 通过 Piezo1/RhoA/Rho 相关卷曲螺旋蛋白激酶 1/Yes1 相关转录调节剂信号通路影响成骨和血管生成。结果表明，Yoda1 双层膜在加速骨再生方面具有高效性和多功能性，提示其作为一种新型治疗剂在各种临床问题中的潜在应用价值。
