PDF(Pubmed)
Abstract：
Diabetic wounds, characterized by prolonged inflammation and impaired vascularization, are a serious complication of diabetes. This study aimed to design a gelatin methacrylate (GelMA) hydrogel for the sustained release of netrin-1 and evaluate its potential as a scaffold to promote diabetic wound healing. The results showed that netrin-1 was highly expressed during the inflammation and proliferation phases of normal wounds, whereas it synchronously exhibited aberrantly low expression in diabetic wounds. Neutralization of netrin-1 inhibited normal wound healing, and the topical application of netrin-1 accelerated diabetic wound healing. Mechanistic studies demonstrated that netrin-1 regulated macrophage heterogeneity via the A2bR/STAT/PPARγ signaling pathway and promoted the function of endothelial cells, thus accelerating diabetic wound healing. These data suggest that netrin-1 is a potential therapeutic target for diabetic wounds.
摘要：
糖尿病伤口,以长期炎症和血管形成受损为特征，是糖尿病的严重并发症。本研究旨在设计一种用于持续释放netrin-1的明胶甲基丙烯酸酯（GelMA）水凝胶，并评估其作为促进糖尿病伤口愈合的支架的潜力。结果显示，netrin-1在正常伤口的炎症和增殖阶段高表达，而它在糖尿病伤口中同时表现出异常低的表达。netrin-1的中和抑制了正常的伤口愈合，局部应用netrin-1加速糖尿病创面愈合。机制研究表明,netrin-1通过A2bR/STAT/PPARγ信号通路调节巨噬细胞异质性,促进内皮细胞功能,从而加速糖尿病伤口的愈合。这些数据表明netrin-1是糖尿病伤口的潜在治疗靶标。
