NTU Institute for Health Technologies, Interdisciplinary Graduate School , Nanyang Technological University , 637553 , Singapore.
School of Chemical and Biomedical Engineering , Nanyang Technological University , 62 Nanyang Drive , 637459 , Singapore.
ACS Appl Mater Interfaces. 2018 Jun 20;10(24):20356-20367. doi: 10.1021/acsami.8b06262. Epub 2018 Jun 7.
Multidrug resistance and the refractory character of bacterial biofilms are among the most difficult challenges in infection treatment. Current antimicrobial strategies typically are much more effective for prevention of biofilm formation than for eradication of established biofilms; these strategies also leave dead bacteria and endotoxin in the infection site, which impairs healing. We report a novel hydrogel that eradicates biofilm bacteria by non-leaching-based debridement followed by ex situ contact-killing (DESCK) away from the infection site. The debridement effect is likely due to the high water swellability and microporosity of the cross-linked network which is made from polyethylene glycol dimethacrylate tethered with a dangling polyethylenimine (PEI) star copolymer. The large pore size of the hydrogel makes the cationic pore walls highly accessible to bacteria. The hydrogel also degrades in the presence of infection cells, releasing star cationic PEI into the infection site to contact-kill bacteria remaining there. DESCK hydrogel effectively kills (>99.9% reduction) biofilms of methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Pseudomonas aeruginosa (CR-PA) and Acinetobacter baumannii in a murine excisional wound infection model. Silver-based wound dressings (controls) showed almost no killing of CR-PA and MRSA biofilms. This DESCK hydrogel greatly reduces the bioburden and inflammation and promotes wound healing. It has great potential for diverse infection treatment applications.
多药耐药性和细菌生物膜的难治性是感染治疗中最困难的挑战之一。目前的抗菌策略通常在预防生物膜形成方面比在消除已建立的生物膜方面更有效；这些策略还会在感染部位留下死细菌和内毒素，从而阻碍愈合。我们报告了一种新型水凝胶，它通过非浸出性清创，随后在远离感染部位的异位接触杀灭（DESCK）来根除生物膜细菌。清创效果可能是由于交联网络的高溶胀性和微孔性所致，该交联网络由与悬垂聚乙烯亚胺（PEI）星形共聚物键合的甲基丙烯酸聚乙二醇二酯制成。水凝胶的大孔径使阳离子孔壁极易接近细菌。在感染细胞存在的情况下，水凝胶也会降解，将星形阳离子 PEI 释放到感染部位，以接触杀灭那里残留的细菌。DESCK 水凝胶在鼠切创感染模型中有效杀灭（>99.9%减少）耐甲氧西林金黄色葡萄球菌（MRSA）和耐碳青霉烯铜绿假单胞菌（CR-PA）和鲍曼不动杆菌生物膜。含银的伤口敷料（对照）对 CR-PA 和 MRSA 生物膜几乎没有杀灭作用。这种 DESCK 水凝胶大大降低了生物负荷和炎症，促进了伤口愈合。它具有广泛的感染治疗应用的巨大潜力。
