Nick Sarah E, Bryers James D, Daggett Valerie
Department of Bioengineering, University of Washington, Seattle, WA, USA.
J Biomed Mater Res A. 2025 Mar;113(3):e37879. doi: 10.1002/jbm.a.37879.
Microbial biofilms on wounds lead to longer hospital stays, mechanical debridement, and higher mortality. Amyloid fibrils stabilize the bacterial biofilm's extracellular matrix (ECM) and represent a potential anti-biofilm target. As previously reported, de novo α-sheet peptides inhibit amyloid fibrillization and reduce biofilm formation in several bacterial species. Alginate (ALG) and chitosan (CH) are widely used in wound dressings due to their adhesive and antimicrobial activity. Here, we describe a layer-by-layer (LbL) functionalized gauze with alternating layers of ALG and CH loaded with α-sheet peptides for controlled release and biofilm inhibition at a wound site. Material analysis indicated successful LbL polyelectrolyte deposition and peptide incorporation. The LbL gauze facilitated controlled peptide release for 72 h with an initial burst delivery and demonstrated good biocompatibility with no toxicity towards human fibroblasts. The LbL gauze was assessed against Escherichia coli biofilms and reduced colony forming units (CFUs) of adherent bacteria by 81% and 96% as compared to the plain gauze for non-antibiotic and antibiotic (+gentamicin) conditions, respectively. A similar reduction in biofilm formation and increase in antibiotic susceptibility was observed for tests with Staphylococcus aureus and vancomycin. Thus, LbL gauze with incorporated α-sheet peptides demonstrated anti-biofilm properties for both gram-negative and gram-positive bacteria and presents an alternative wound dressing for the prevention of biofilm-associated infections.
伤口上的微生物生物膜会导致住院时间延长、需要进行机械清创以及死亡率升高。淀粉样纤维可稳定细菌生物膜的细胞外基质（ECM），是一种潜在的抗生物膜靶点。如先前报道，从头合成的α-折叠肽可抑制淀粉样纤维化，并减少多种细菌中的生物膜形成。藻酸盐（ALG）和壳聚糖（CH）因其具有黏附性和抗菌活性而被广泛用于伤口敷料。在此，我们描述了一种逐层（LbL）功能化纱布，其具有交替的ALG层和CH层，并负载了α-折叠肽，用于在伤口部位实现控释和生物膜抑制。材料分析表明成功进行了LbL聚电解质沉积和肽掺入。LbL纱布在初始的快速释放后实现了72小时的肽控释，并表现出良好的生物相容性，对人成纤维细胞无毒性。对LbL纱布针对大肠杆菌生物膜进行了评估，在非抗生素和抗生素（+庆大霉素）条件下，与普通纱布相比，附着细菌的菌落形成单位（CFU）分别减少了81%和96%。在对金黄色葡萄球菌和万古霉素的测试中，也观察到生物膜形成有类似的减少以及抗生素敏感性增加。因此，掺入α-折叠肽的LbL纱布对革兰氏阴性菌和革兰氏阳性菌均表现出抗生物膜特性，为预防生物膜相关感染提供了一种替代的伤口敷料。
