Enhanced diabetic wound repair remained a global challenge. Herein, we reported a novel hydrogel with glucose-responsive hyperglycemia regulation and antioxidant activity for enhanced diabetic wound repair. In this study, gallic acid (GA) with strong antioxidant activity was grafted onto chitosan (CS) chains by one-step synthesis, and then incorporated into poly (ethylene glycol) diacrylate (PEG-DA) hydrogel matrix to obtain a novel antioxidant hybrid hydrogel (PEG-DA/CS-GA). Meanwhile, polyethyleneimine (PEI) was modified with a unique glucose-sensitive phenylboronic acid (PBA) molecule to load insulin (PEI-PBA/insulin nano-particles, PEI-PBA/insulin NPs), which could be immobilized in the PEG-DA/CS-GA hybrid hydrogel by the formation of dynamic borate bond between the phenylboronic acid groups on the PEI-PBA and the polyphenol groups on the CS-GA. The results indicated that the PEG-DA/PEI-PBA/insulin/CS-GA (PPIC) hydrogel platform not only had remarkable biocompatibility, but also displayed extraordinary antioxidant properties (DPPH scavenging rate > 95.0%), and effectively protected cells from oxidative damage (decreased MDA levels, increased Superoxide dismutase (SOD) levels and stable GSH/GSSG levels). Meanwhile, the PPIC hydrogel also exhibited unique glucose-responsive insulin release characteristics, and effectively regulated the blood glucose level. The in vitro and in vivo results demonstrated that our PPIC hydrogel could promoted angiogenesis (increased VEGF and CD 31 expression), reshaped the inflammatory microenvironment (decreased IL-6 and increased IL-10 level), and achieved wound closure within 20 days. All these results strongly indicated that the PPIC hydrogel represented a tough and efficient platform for diabetic wound treatment.

增强糖尿病伤口修复仍然是一项全球性挑战。在此，我们报道了一种具有葡萄糖响应性高血糖调节和抗氧化活性的新型水凝胶，用于增强糖尿病伤口修复。本研究通过一步合成将具有强抗氧化活性的没食子酸（GA）接枝到壳聚糖（CS）链上，然后掺入聚（乙二醇）二丙烯酸酯（PEG-DA）水凝胶基质中，得到一种新型抗氧化杂化物水凝胶（PEG-DA/CS-GA）。同时，聚乙烯亚胺（PEI）被一种独特的葡萄糖敏感性苯基硼酸（PBA）分子修饰以负载胰岛素（PEI-PBA/insulin nano-particles，PEI-PBA/insulin NPs），通过在 PEI-PBA 上的苯基硼酸基团和 CS-GA 上的多酚基团之间形成动态硼酸盐键，可以将其固定在 PEG-DA/CS-GA 杂化水凝胶中。结果表明，PEG-DA/PEI-PBA/insulin/CS-GA（PPIC）水凝胶平台不仅具有显着的生物相容性，而且表现出非凡的抗氧化性能（DPPH清除率> 95.0%），有效保护细胞免受氧化。损害（降低 MDA 水平，增加超氧化物歧化酶 (SOD) 水平和稳定的 GSH/GSSG 水平）。同时，PPIC水凝胶还表现出独特的葡萄糖反应性胰岛素释放特性，有效调节血糖水平。这 但也表现出非凡的抗氧化特性（DPPH 清除率 > 95.0%），并有效保护细胞免受氧化损伤（降低 MDA 水平，增加超氧化物歧化酶 (SOD) 水平和稳定的 GSH/GSSG 水平）。同时，PPIC水凝胶还表现出独特的葡萄糖反应性胰岛素释放特性，有效调节血糖水平。这 但也表现出非凡的抗氧化特性（DPPH 清除率 > 95.0%），并有效保护细胞免受氧化损伤（降低 MDA 水平，增加超氧化物歧化酶 (SOD) 水平和稳定的 GSH/GSSG 水平）。同时，PPIC水凝胶还表现出独特的葡萄糖反应性胰岛素释放特性，有效调节血糖水平。这体外和体内结果表明，我们的 PPIC 水凝胶可以促进血管生成（增加 VEGF 和 CD 31 表达），重塑炎症微环境（降低 IL-6 和增加 IL-10 水平），并在 20 天内实现伤口闭合。所有这些结果都强烈表明，PPIC 水凝胶代表了糖尿病伤口治疗的坚韧有效的平台。