通过激活 cGAS-STING 通路构建纳米纤维状溶菌酶水凝胶以免疫记忆抗糖尿病伤口感染复发的二价阴离子通用凝胶化策略

Aggregate Pub Date : 2024-09-05 DOI:10.1002/agt2.662
Aihui Wang, Liqun Li, Liqian Zheng, Bang‐Ping Jiang, Yihao Liu, Rimei Huang, Huimin Qiu, Shichen Ji, Hong Liang, Xing‐Can Shen
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摘要

抗菌溶菌酶水凝胶因其固有的抗菌活性以及优异的生化和机械性能,在伤口敷料中显示出诱人的优势。遗憾的是,由于缺乏通用的凝胶化策略,这类水凝胶的开发仍然受到很大限制。本文首次提出了溶菌酶-纳米纤维(LZF)与无机盐之间的通用凝胶化策略,以构建功能性纳米纤维溶菌酶水凝胶。特别是发现二价阴离子通过静电作用普遍驱动 LZF 聚合并转化为三维纳米纤维状网络水凝胶,并通过分子动力学模拟进一步证明了二价阴离子在凝胶化过程中的关键作用。此外,LZF 还被赋予了近红外光介导的光热特性,通过与基因素进行骨架修饰,生成了基因素诱导的 LZF(GLZF),从而增强了其对多重耐药细菌的抑制活性。作为一种独特的应用范例,MnSO4 交联的 GLZF 水凝胶具有出色的免疫记忆功能,能敏化 cGAS-STING 通路,巧妙地建立抗菌免疫微环境。它能通过光增强细菌杀伤和 cGAS-STING 通路出色地实现糖尿病伤口感染的抗复发。因此,它为未来采用通用的二价阴离子介导凝胶化策略开发功能性无机盐杂化溶菌酶水凝胶铺平了道路。
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A universal gelation strategy of bivalent anions to construct nanofibrous lysozyme hydrogels for immunomemory anti‐recurrence of diabetic wound infection by activating the cGAS‐STING pathway
Antibacterial lysozyme hydrogels show attractive advantages in wound dressings due to their intrinsic antibacterial activity and excellent biochemical and mechanical properties. Unfortunately, the development of such hydrogels is still greatly limited due to the lack of universal gelation strategies. Herein, a universal gelation strategy between lysozyme‐nanofiber (LZF) and inorganic salts is proposed for the first time to construct functional nanofibrous lysozyme‐based hydrogels. In particular, divalent anions are found to universally drive LZF for the aggregation and transformation into three‐dimensional nanofibrous network hydrogels via electrostatic interaction, and the key role of divalent anions in the gelation is further proved by molecular dynamics simulation. In addition, near‐infrared light‐mediated photothermal characteristics are endowed with LZF to enhance its inhibitory activity of multidrug‐resistant bacteria by the skeleton modification with genipin to produce genipin‐conjuagted LZF (GLZF). As a distinct application paradigm, the brilliant immunomemory MnSO4‐crosslinked GLZF hydrogel is constructed to sensitize the cGAS‐STING pathway and skillfully establish an antibacterial immune microenvironment. It can excellently realize the anti‐recurrence of diabetic wound infection via photo‐enhanced bacterial killing and the cGAS‐STING pathway. Thereby, it paves the way to employ the universal divalent anion‐mediated gelation strategy for the future development of functional inorganic salt hybrid lysozyme hydrogels.
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