Wound microenvironment self-adaptive hydrogel with efficient angiogenesis for promoting diabetic wound healing

• Published in: Bioactive materials Vol. 20; pp. 561 - 573
• Main Authors: Shao, Zijian, Yin, Tianyu, Jiang, Jinbo, He, Yang, Xiang, Tao, Zhou, Shaobing
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.02.2023; KeAi Publishing; KeAi Communications Co., Ltd
• Subjects: Angiogenesis; Diabetic wound healing; MMP-9 responsive; Self-adaptive hydrogel; Wound microenvironment; Angiogenesis; Self-adaptive hydrogel; Wound microenvironment; MMP-9 responsive; Diabetic wound healing
• ISSN: 2452-199X; 2452-199X
• DOI: 10.1016/j.bioactmat.2022.06.018

Neovascularization is critical to improve the diabetic microenvironment, deliver abundant nutrients to the wound and promote wound closure. However, the excess of oxidative stress impedes the healing process. Herein, a self-adaptive multifunctional hydrogel with self-healing property and injectability is fabricated through a boronic ester-based reaction between the phenylboronic acid groups of the 3-carboxyl-4-fluorophenylboronic acid -grafted quaternized chitosan and the hydroxyl groups of the polyvinyl alcohol, in which pro-angiogenic drug of desferrioxamine (DFO) is loaded in the form of gelatin microspheres (DFO@G). The boronic ester bonds of the hydrogel can self-adaptively react with hyperglycemic and hydrogen peroxide to alleviate oxidative stress and release DFO@G in the early phase of wound healing. A sustained release of DFO is then realized by responding to overexpressed matrix metalloproteinases. In a full-thickness diabetic wound model, the DFO@G loaded hydrogel accelerates angiogenesis by upregulating expression of hypoxia-inducible factor-1 and angiogenic growth factors, resulting in collagen deposition and rapid wound closure. This multifunctional hydrogel can not only self-adaptively change the microenvironment to a pro-healing state by decreasing oxidative stress, but also respond to matrix metalloproteinases to release DFO. The self-adaptive multifunctional hydrogel has a potential for treating diabetic wounds. [Display omitted] •Injectable self-healing hydrogel was prepared based on boronic ester-based reaction.•The hydrogel could self-adaptively regulate the microenvironment to a pro-healing state.•The hydrogel could efficiently promoting diabetic wound healing by accelerating angiogenesis.