Wang Yixi, Song Ping, Wu Lina, Su Zixuan, Gui Xingyu, Gao Canyu, Zhao Hanxing, Wang Yudong, Li Zhengyong, Cen Ying, Pan Bo, Zhang Zhenyu, Zhou Changchun
Department of Burn and Plastic Surgery, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China.
National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, China.
J Mater Chem B. 2023 Jan 25;11(4):837-851. doi: 10.1039/d2tb02371g.
The delayed healing of diabetic wounds is directly affected by the disturbance of wound microenvironment, resulting from persistent inflammation, insufficient angiogenesis, and impaired cell functions. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) showed considerable therapeutic potential in diabetic wound healing. However, the low retention rate of MSC-EVs at wound sites hampers their efficacy. For skin wounds exposed to the outer environment, using a hydrogel with tissue adhesiveness under a moist wound condition is a promising strategy for wound healing. In this study, we modified methacryloyl-modified gelatin (GelMA) hydrogel with catechol motifs of dopamine to fabricate a GelMA-dopamine hydrogel. EVs isolated from MSCs were applied in the synthesized GelMA-dopamine hydrogel to prepare a GelMA-dopamine-EV hydrogel. The results demonstrated that the newly formed GelMA-dopamine hydrogel possessed improved properties of softness, adhesiveness, and absorptive capacity, as well as high biocompatibility in the working concentration (15% w/v). In addition, MSC-EVs were verified to promote cell migration and angiogenesis . In the skin wound model of diabetic rats, the GelMA-dopamine-EV hydrogel exerted prominent wound healing efficacy estimated by collagen deposition, skin appendage regeneration, and the expression of IL-6, CD31, and TGF-β. In conclusion, this combination of MSC-EVs and the modified hydrogel not only accelerates wound closure but also promotes skin structure normalization by rescuing the homeostasis of the healing microenvironment of diabetic wounds, which provides a potential approach for the treatment of diabetic wounds.
糖尿病伤口愈合延迟直接受到伤口微环境紊乱的影响，这种紊乱是由持续炎症、血管生成不足和细胞功能受损引起的。间充质干细胞衍生的细胞外囊泡（MSC-EVs）在糖尿病伤口愈合中显示出相当大的治疗潜力。然而，MSC-EVs在伤口部位的低保留率阻碍了它们的疗效。对于暴露于外部环境的皮肤伤口，在湿润伤口条件下使用具有组织粘附性的水凝胶是一种有前景的伤口愈合策略。在本研究中，我们用多巴胺的邻苯二酚基序修饰甲基丙烯酰化明胶（GelMA）水凝胶，制备了GelMA-多巴胺水凝胶。将从间充质干细胞分离的细胞外囊泡应用于合成的GelMA-多巴胺水凝胶中，制备了GelMA-多巴胺-EV水凝胶。结果表明，新形成的GelMA-多巴胺水凝胶具有改善的柔软性、粘附性和吸收能力，以及在工作浓度（15% w/v）下的高生物相容性。此外，已证实MSC-EVs可促进细胞迁移和血管生成。在糖尿病大鼠的皮肤伤口模型中，通过胶原沉积、皮肤附属器再生以及IL-6、CD31和TGF-β的表达评估，GelMA-多巴胺-EV水凝胶发挥了显著的伤口愈合疗效。总之，这种MSC-EVs与修饰水凝胶的组合不仅加速伤口闭合，还通过挽救糖尿病伤口愈合微环境的稳态促进皮肤结构正常化，这为糖尿病伤口的治疗提供了一种潜在方法。
