Netrin-1 co-cross-linked hydrogel accelerates diabetic wound healing in situ by modulating macrophage heterogeneity and promoting angiogenesis

Futing Shu; Hongchao Huang; Shichu Xiao; Zhaofan Xia; Yongjun Zheng

Bioactive Materials (Sep 2024)

Netrin-1 co-cross-linked hydrogel accelerates diabetic wound healing in situ by modulating macrophage heterogeneity and promoting angiogenesis

Futing Shu,
Hongchao Huang,
Shichu Xiao,
Zhaofan Xia,
Yongjun Zheng

Affiliations

Futing Shu: Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, People's Republic of China
Hongchao Huang: Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, People's Republic of China
Shichu Xiao: Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, People's Republic of China; Corresponding author. Department of Burn Surgery, the First Affiliated Hospital of Naval Medical University, 168 Changhai Road, Yangpu District, Shanghai, 200433, People's Republic of China.
Zhaofan Xia: Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, People's Republic of China; Research Unit of Key Techniques for Treatment of Burns and Combined Burns and Trauma Injury, Chinese Academy of Medical Sciences, Shanghai, 200433, People's Republic of China; Corresponding author. Department of Burn Surgery, the First Affiliated Hospital of Naval Medical University, 168 Changhai Road, Yangpu District, Shanghai, 200433, People's Republic of China.
Yongjun Zheng: Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, People's Republic of China; Corresponding author. Department of Burn Surgery, the First Affiliated Hospital of Naval Medical University, 168 Changhai Road, Yangpu District, Shanghai, 200433, People's Republic of China.

Journal volume & issue: Vol. 39
pp. 302 – 316

Abstract

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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.

Published in Bioactive Materials

ISSN: 2452-199X (Online)
Publisher: KeAi Communications Co., Ltd.
Country of publisher: China
LCC subjects: Technology: Electrical engineering. Electronics. Nuclear engineering: Materials of engineering and construction. Mechanics of materials; Science: Biology (General)
Website: https://www.keaipublishing.com/en/journals/bioactive-materials/

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