Enhanced therapeutic effects of mesenchymal stem cell-derived extracellular vesicles within chitosan hydrogel in the treatment of diabetic foot ulcers

作者：Shuangshuang Yang, Siyu Chen, Chengpeng Zhang, Jing Han, Chun‐Yuan Lin, Xiaohui Zhao, Huizhen Guo, Yi Tan · 发表于：Journal of Materials Science Materials in Medicine · 年份：2023 · DOI：10.1007/s10856-023-06746-y · 被引用次数：16 · 研究领域：Extracellular vesicles in disease、Wound Healing and Treatments、Mesenchymal stem cell research

Extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (hUCMSCs) have emerged as promising candidates for cell-free therapy in various diseases, including chronic cutaneous wounds. However, the lack of standardized protocols for EVs' preparation and identification poses a significant challenge to their clinical application. Thus, the objective was to develop a safe and efficient method for the large-scale production of hUCMSC-derived EVs while establishing a comprehensive identification protocol encompassing morphology, particle size distribution, protein expression, and purity. This study observed that most of the EVs acquired through the protocol exhibited either a cup-shaped or round-shaped structure, with a median diameter of ~73.25 nm. The proportions of EVs positive for CD9, CD63, and CD81 were 37.5%, 38.6%, and 19.8%, respectively. To enhance their therapeutic potential in wound treatment, EVs were incorporated into chitosan hydrogel, forming chitosan hydrogel-EVs (CS-EVs). Furthermore, it was demonstrated that CS-EVs exhibited continuous release of EVs into the surrounding environment and, importantly, that the released EVs were internalized by human umbilical vein endothelial cells (HUVECs), resulting in significant enhancement of cell migration and angiogenesis. Additionally, in a rat model of diabetic foot ulcers, CS-EVs demonstrated a robust therapeutic effect in promoting wound healing. Following a 15-day treatment period, the group...