School of Chemical Science and Engineering, Fiber and Polymer Technology, KTH Royal Institute of Technology, Teknikringen 56-58, SE-100 44 Stockholm, Sweden.
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-17165 Stockholm, Sweden.
J Am Chem Soc. 2021 Oct 20;143(41):17180-17190. doi: 10.1021/jacs.1c07492. Epub 2021 Oct 12.
Infections caused by antibiotic-resistant bacteria are globally a major threat, leading to high mortality rates and increased economic burden. Novel treatment strategies are therefore urgently needed by healthcare providers to protect people. Biomaterials that have inherent antibacterial properties and do not require the use of antibiotics present an attractive and feasible avenue to achieve this goal. Herein, we demonstrate the effect of a new class of cationic hydrogels based on amino-functional hyperbranched dendritic-linear-dendritic copolymers (HBDLDs) exhibiting excellent antimicrobial activity toward a wide range of clinical Gram-positive and Gram-negative bacteria, including drug-resistant strains isolated from wounds. Intriguingly, the hydrogels can induce the expression of the antimicrobial peptides RNase 7 and psoriasin, promoting host-mediated bacterial killing in human keratinocytes (HaCaT). Moreover, treatment with the hydrogels decreased the proinflammatory cytokine IL-1β, reactive nitrogen species (NO), and mitochondrial reactive oxygen species (ROS) in -infected HaCaT cells, conjunctively resulting in reduced inflammation.
抗生素耐药菌引起的感染在全球范围内是一个主要威胁，导致高死亡率和经济负担增加。因此，医疗保健提供者迫切需要新的治疗策略来保护人们。具有固有抗菌特性且无需使用抗生素的生物材料为实现这一目标提供了一种有吸引力和可行的途径。在此，我们展示了一类新型阳离子水凝胶的效果，该水凝胶基于具有支化线性树枝状嵌段共聚物（HBDLD）的氨基功能化超支化的，对多种临床革兰氏阳性和革兰氏阴性菌具有优异的抗菌活性，包括从伤口中分离出的耐药菌株。有趣的是，水凝胶可以诱导抗菌肽 RNase 7 和 psoriasin 的表达，从而促进人角质形成细胞（HaCaT）中宿主介导的细菌杀伤。此外，水凝胶处理降低了感染的 HaCaT 细胞中的促炎细胞因子 IL-1β、活性氮物种 (NO) 和线粒体活性氧 (ROS)，从而减少了炎症。
