Abstract：
Developing effective methods for alveolar bone defect regeneration is a significant challenge in orthopedics. Exosomes from human umbilical cord mesenchymal stem cells (HUMSC-Exos) have shown potential in bone repair but face limitations due to undefined application methods and mechanisms. To address this, HUMSC-Exos were encapsulated in polyvinyl alcohol (PVA) hydrogel (Exo@PVA) to create a novel material for alveolar bone repair. This combination enhanced the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) more effectively than Exos alone. Additionally, Exo@PVA significantly improved alveolar bone regeneration and defect repair in rats. The microRNA-21-5p (miR-21-5p) in Exo@PVA, identified through the GEO database and analyzed via in silico methods, played a crucial role. miR-21-5p promoted BMSC osteogenic differentiation by inhibiting WWP1-mediated KLF5 ubiquitination and enhanced HUVEC angiogenesis by targeting ATP2B4. These findings underscore the potential of an Exo-based approach with PVA hydrogel scaffolds for bone defect repair, operating through the miR-21-5p/WWP1/ATP2B4 signaling axis.
摘要：
开发有效的牙槽骨缺损再生方法是骨科的重大挑战。来自人脐带间充质干细胞（HUMSC-Exos）的外泌体已显示出在骨修复中的潜力，但由于不确定的应用方法和机制而面临局限性。为了解决这个问题，将HUMSC-Exos封装在聚乙烯醇（PVA）水凝胶（Exo@PVA）中以创建用于牙槽骨修复的新型材料。这种组合比单独的Exos更有效地增强了骨髓间充质干细胞（BMSCs）和人脐静脉内皮细胞（HUVECs）的成骨分化。此外,Exo@PVA显著改良年夜鼠牙槽骨再生和缺损修复。Exo@PVA中的microRNA-21-5p（miR-21-5p）通过GEO数据库识别并通过计算机模拟方法进行分析，发挥了至关重要的作用。miR-21-5p通过抑制WWP1介导的KLF5泛素化促进BMSC成骨分化，并通过靶向ATP2B4增强HUVEC血管生成。这些发现强调了基于Exo的PVA水凝胶支架修复骨缺损的潜力，通过miR-21-5p/WWP1/ATP2B4信号轴操作。
