The graphene oxide/alginate gel loaded with platelet-rich plasma-derived exosomes regulate notch 1 signaling pathway to promote diabetic foot wound healing

Exosomes have promising applications in accelerating wound healing; however, it remains a challenge for exosomes to effectively promote healing of damaged wounds such as diabetic foot ulcers. The aim of this study was to produce an exosome that promotes wound healing in diabetic foot ulcers and to investigate its potential mechanism. Firstly, graphene oxide/alginate gel loaded with platelet-rich plasma-derived exosomes (GO/Alg + Exo) was prepared and characterized, and then the cytotoxicity and function of the gel were detected in vitro by cell survival, immunofluorescence and scratch test. In vitro experiments were performed to investigate the molecular mechanism of GO/Alg + Exo in promoting diabetic wound healing. Finally, an animal model of diabetic foot ulcer was prepared to study the bioactivity of the gel and the molecular mechanism in vivo. GO/Alg + Exo can promote skin fibrosis, enhance cell proliferation, reduce apoptosis, and promote neoangiogenesis to promote the skin repair of diabetic chronic wounds. In addition, in vitro and in vivo experiments demonstrated that GO/Alg + Exo could promote cell proliferation and angiogenesis by regulating the Notch 1 signaling pathway. GO/Alg + Exo promotes the healing of diabetic foot ulcer wounds by inhibiting the Notch 1 signaling pathway.