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...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/PPARγsignaling 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.展开更多
基金supported by 173 plan project of Military Science and Technology(2019-JCJQ-ZD-359-00)the National Key R&D Program of China(2019YFA0110503,2019YFA0110501)+5 种基金the National Nature Science Foundation of China(82072170,82372512,82172201,82372513,81930057 and 81701905)Shanghai Rising Star Program(22QA1411700)Basic medical research project of Changhai Hospital(2023YQ02)Changhong talent plan of Changhai HospitalYouth Medical Talents-Specialist ProgramChinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2019-I2M-5-076).
文摘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/PPARγsignaling 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.
