Fang Zheng, He Qingyan, Hu Yanyu, Chen Xu, Li Fan, Cai Xixi
Institute of Molecular Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
College of Biological Science and Engineering, Fuzhou University, Fuzhou 350108, China.
J Adv Res. 2025 Jul;73:283-294. doi: 10.1016/j.jare.2024.08.025. Epub 2024 Aug 19.
Wound infections and formation of biofilms caused by multidrug-resistant bacteria have constituted a series of wound deteriorated and life-threatening problems. The in situ resisting bacterial adhesion, killing multidrug-resistance bacteria, and releasing dead bacteria is strongly required to supply a gap of existing sterilization strategies.
This study aims to present a facile approach to construct a bacteria-responsive hydrogel with switchable antimicrobial-antifouling properties through a "resisting-killing-releasing" method.
The smart bacteria-responsive hydrogel was constructed by two-step immersion strategy: a simple immersion-coating process to construct Polydopamine (pDA) coatings on the surface of a gelatin-chitosan composite hydrogel and followed by grafting of bactericidal quaternary ammonium chitosan (QCS) as well as pH-responsive PMAA to this pDA coating. The in vitro antimicrobial activity, biocompatibility and the in vivo wound healing effects in a mouse MRSA-infected full-thickness defect model of the hydrogel were further evaluated.
Assisted by polydopamine coating, the pH-responsive PMAA and bactericidal QCS are successfully grafted onto a gelatin-chitosan composite hydrogel surface and hydrogels maintain the adequate mechanical properties. At physiological conditions, the PMAA hydration layer endows the hydrogel with resistance to initial bacterial attachment. Once bacteria colonize and acidize local environment, the swelling PMAA chains tend to collapse then expose the bactericidal QCS, realizing the on-demand kill bacteria. Moreover, the dead bacteria can be released and the hydrogel will resume the resistance due to hydrophilicity of PMAA at increased pH, endowing the surface renewable ability. In vitro and in vivo studies demonstrate the favorable biocompatibility and wound healing capacity of hydrogels that can inhibit infection and further facilitate granulation tissue, angiogenesis, and collagen synthesis.
This strategy provides a novel methodology for the development and design of smart wound dressing to combat multidrug-resistant bacteria infections.
由多重耐药菌引起的伤口感染和生物膜形成已构成一系列伤口恶化和危及生命的问题。迫切需要原位抵抗细菌粘附、杀灭多重耐药菌并释放死亡细菌，以弥补现有杀菌策略的不足。
本研究旨在提出一种简便的方法，通过“抵抗-杀灭-释放”方法构建具有可切换抗菌-防污性能的细菌响应水凝胶。
通过两步浸泡策略构建智能细菌响应水凝胶：首先通过简单的浸泡涂层工艺在明胶-壳聚糖复合水凝胶表面构建聚多巴胺（pDA）涂层，然后将杀菌季铵壳聚糖（QCS）以及pH响应性聚甲基丙烯酸（PMAA）接枝到该pDA涂层上。进一步评估了水凝胶在体外的抗菌活性、生物相容性以及在小鼠耐甲氧西林金黄色葡萄球菌感染的全层缺损模型中的体内伤口愈合效果。
在聚多巴胺涂层的辅助下，pH响应性PMAA和杀菌QCS成功接枝到明胶-壳聚糖复合水凝胶表面，水凝胶保持了足够的机械性能。在生理条件下，PMAA水合层赋予水凝胶抵抗初始细菌附着的能力。一旦细菌定植并酸化局部环境，膨胀的PMAA链会趋于塌陷，从而暴露出杀菌QCS，实现按需杀灭细菌。此外，死亡细菌可以被释放，并且由于pH升高时PMAA的亲水性，水凝胶将恢复抗性，赋予表面可再生能力。体外和体内研究表明，水凝胶具有良好的生物相容性和伤口愈合能力，能够抑制感染并进一步促进肉芽组织、血管生成和胶原蛋白合成。
该策略为开发和设计用于对抗多重耐药菌感染的智能伤口敷料提供了一种新方法。
