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

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

  • Toxicol Appl Pharmacol. 2025 Nov:504:117536. doi: 10.1016/j.taap.2025.117536.
Ningjie Chen 1 Doudou Chai 2 Liping Gao 2 Wei Zhang 3 Haitao Wang 4 Jincun Yang 5 Xiuxiang Yu 1 Shuang Yan 3 Qingpeng Xu 3 Siqing Wang 2
Affiliations

Affiliations

  • 1 Department of Burns and Plastic Surgery, Weihai Municipal Hospital, Shandong University, Shandong 264200, China.
  • 2 Department of Burns and Plastic Surgery, Weihai Municipal Hospital, Shandong University, Shandong 264200, China; The Second Clinical Medical College of Binzhou Medical University, Shandong 264100, China.
  • 3 Department of Burns and Plastic Surgery, Weihai Municipal Hospital, Shandong University, Shandong 264200, China; Institute of Plastic Surgery, Shandong Second Medical University, Shandong 261031, China.
  • 4 Department of Burns and Plastic Surgery, Weihai Municipal Hospital, Shandong University, Shandong 264200, China; The Second Clinical Medical College of Binzhou Medical University, Shandong 264100, China; Institute of Plastic Surgery, Shandong Second Medical University, Shandong 261031, China. Electronic address: haitaowangwh@163.com.
  • 5 Department of Burns and Plastic Surgery, Weihai Municipal Hospital, Shandong University, Shandong 264200, China. Electronic address: 18660377576@163.com.
Abstract

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.

Keywords

Diabetic foot ulcers; Fibrosis; Graphene oxide/alginate gel; Notch 1 pathway.

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