Three-dimensional cell culture-derived extracellular vesicles loaded alginate/hyaluronic acid composite scaffold as an optimal therapy for cartilage defect regeneration

作者：Wanting Zhang, Shuyi Li, Y. Y. Peng, Zhujie Deng, Quanjiang Li, Rui Tian, Xiubin Kuang, Yuyi Kang, Ronghui Sun, Chen Huang, Zhengqiang Yuan · 发表于：Biomedical Materials · 年份：2025 · DOI：10.1088/1748-605x/adb22e · 被引用次数：8 · 研究领域：Extracellular vesicles in disease、Osteoarthritis Treatment and Mechanisms、Knee injuries and reconstruction techniques

Abstract Osteoarthritis (OA) is a chronic musculoskeletal disease characterized by joint inflammation and progressive degeneration of articular cartilage. Currently a definitive cure for OA remains to be a challenge due to the very low self-repair capacity of cartilage, thus development of more effective therapies is needed for cartilage repair. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have shown great potential as therapeutic agents for stimulating regeneration of articular cartilage. However, a standardized protocol is still lacking for manufacturing of highly active EVs for clinical applications. This study aimed to investigate the efficient production of highly active EVs by 3-dimensional (3D) MSC culture, verify the reparative efficacy of EVs on cartilage defect and elucidate the repair mechanisms. Umbilical cord MSCs were embedded in alginate to form MSC spheroids for 3D culture in human platelet lysate (hPL)-containing medium, which produced 3D culture-derived EVs (3D-EVs) with a significantly improved yield. The 3D-EVs expressed higher level of VEGF, and appeared superior to two-dimensional (2D) monolayer MSC culture-derived EVs (2D-EVs) to improve migration and proliferation in MSCs and inflammatory chondrocytes, and to suppress expression of cartilage-degrading factors. Importantly, the 3D-EVs and sodium alginate (SA)-hyaluronic acid (HA) composite hydrogel (3D-EVs/SA-HA) demonstrated significantly improved therapeutic efficacy than 2D-EVs/SA-H...