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负载葡萄糖氧化酶@沸石咪唑酯骨架材料-8的葡萄糖响应性多功能水凝胶用于一氧化氮/锌介导的抗菌和促血管生成的糖尿病伤口愈合

Glucose-responsive multifunctional hydrogel incorporating GOx@ZIF-8 for NO/Zn-mediated antibacterial and pro-angiogenic diabetic wound healing.

作者信息

Pan Jialiang, Liu Chenhong, Wang Zhiqiang, Shi Wenbo, Zhao Tianhao, Wei Qingcong, Zhang Qing, Bai Zhengyu

机构信息

Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education; School of Chemistry and Chemical Engineering, Henan Normal University, Henan, Xinxiang 453007, PR China.

Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education; School of Chemistry and Chemical Engineering, Henan Normal University, Henan, Xinxiang 453007, PR China.

出版信息

J Colloid Interface Sci. 2025 Dec 15;700(Pt 1):138423. doi: 10.1016/j.jcis.2025.138423. Epub 2025 Jul 12.

DOI:10.1016/j.jcis.2025.138423
PMID:40674994
Abstract

The hyperglycemic microenvironment of diabetic chronic wounds is a major driver of severe bacterial infections, excessive inflammatory responses, and impaired angiogenesis, all of which delay wound healing. To address these challenges, we prepared a glucose oxidase (GOx)-loaded zeolitic imidazolate framework-8 (GOx@ZIF-8). Furthermore, a multifunctional hydrogel (AACZ) was fabricated by incorporating 5-methylfurfural- and L-arginine-grafted alginate and maleimide-grafted chondroitin sulfate with GOx@ZIF-8 through the Diels-Alder reaction. Results showed that immobilized GOx remained active for a longer time than of free GOx. At the wound site, GOx catalyzed the conversion of excess glucose to gluconic acid and hydrogen peroxide (HO). The reduced pH in the local region induced Zn release from zeolitic imidazolate framework-8, simultaneously, HO mediated the generation of nitric oxide (NO) from L-arginine. The synergy between Zn and NO endowed AACZ with excellent antibacterial properties. The biocompatible hydrogel promoted cell proliferation and migration, regulated local blood glucose levels, inhibited bacterial activity, alleviated inflammation and promoted angiogenesis and collagen deposition at the diabetic wound site. These findings suggest that AACZ holds promise as a responsive dressing material in healing for complex wounds.

摘要

糖尿病慢性伤口的高血糖微环境是严重细菌感染、过度炎症反应和血管生成受损的主要驱动因素,所有这些都会延迟伤口愈合。为应对这些挑战,我们制备了负载葡萄糖氧化酶(GOx)的沸石咪唑酯骨架-8(GOx@ZIF-8)。此外,通过狄尔斯-阿尔德反应将5-甲基糠醛和L-精氨酸接枝的海藻酸盐以及马来酰亚胺接枝的硫酸软骨素与GOx@ZIF-8结合,制备了一种多功能水凝胶(AACZ)。结果表明,固定化的GOx比游离的GOx保持活性的时间更长。在伤口部位,GOx催化过量葡萄糖转化为葡萄糖酸和过氧化氢(HO)。局部区域pH值的降低诱导了沸石咪唑酯骨架-8中锌的释放,同时,HO介导L-精氨酸生成一氧化氮(NO)。锌和NO之间的协同作用赋予了AACZ优异的抗菌性能。这种生物相容性水凝胶促进细胞增殖和迁移,调节局部血糖水平,抑制细菌活性,减轻炎症,并促进糖尿病伤口部位的血管生成和胶原蛋白沉积。这些发现表明,AACZ有望作为一种响应性敷料材料用于复杂伤口的愈合。

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