Turner Adam Benedict, Zermeño-Pérez David, Mysior Margaritha M, Giraldo-Osorno Paula Milena, García Begoña, O'Gorman Elizabeth, Oubihi Shafik, Simpson Jeremy C, Lasa Iñigo, Ó Cróinín Tadhg, Trobos Margarita
Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Centre for Antibiotic Resistance Research in Gothenburg (CARe), Gothenburg, Sweden.
Biofilm. 2024 Oct 5;8:100228. doi: 10.1016/j.bioflm.2024.100228. eCollection 2024 Dec.
Biodegradable polymeric coatings are being explored as a preventive strategy for orthopaedic device-related infection. In this study, titanium surfaces (Ti) were coated with poly-D,L-lactide (PDLLA, (P)), polyethylene-glycol poly-D,L-lactide PEGylated-PDLLA, (PP20)), or multi-layered PEGylated-PDLLA (M), with or without 1 % silver sulfadiazine. The aim was to evaluate their cytocompatibility, resistance to biofilm formation, and their potential to enhance the susceptibility of any biofilm formed to antibiotics. Using automated high-content screening confocal microscopy, biofilm formation of a clinical methicillin-resistant (MRSA) isolate expressing GFP was quantified, along with isogenic mutants that were unable to form polysaccharidic or proteinaceous biofilm matrices. The results showed that PEGylated-PDLLA coatings exhibited significant antibiofilm properties, with M showing the highest effect. This inhibitory effect was stronger in biofilms with a matrix composed of proteins compared to those with an exopolysaccharide (PIA) biofilm matrix. Our data suggest that the antibiofilm effect may have been due to (i) inhibition of the initial attachment through microbial surface components recognising adhesive matrix molecules (MSCRAMMs), since PEG reduces protein surface adsorption via surface hydration layer and steric repulsion; and (ii) mechanical disaggregation and dispersal of microcolonies due to the bioresorbable/degradable nature of the polymers, which undergo hydration and hydrolysis over time. The disruption of biofilm morphology by the PDLLA-PEG co-polymers increased susceptibility to antibiotics like rifampicin and fusidic acid. Adding 1 % AgSD provided additional early bactericidal effects on both biofilm and planktonic . Additionally, the coatings were cytocompatible with immune cells, indicating their potential to enhance bacterial clearance and reduce bacterial colonisation of titanium-based orthopaedic biomaterials.
可生物降解的聚合物涂层正在作为预防骨科器械相关感染的一种策略进行探索。在本研究中，钛表面（Ti）被涂上聚-D,L-丙交酯（PDLLA，(P)）、聚乙二醇聚-D,L-丙交酯聚乙二醇化-PDLLA（(PP20)）或多层聚乙二醇化-PDLLA（M），有或没有1%的磺胺嘧啶银。目的是评估它们的细胞相容性、对生物膜形成的抗性以及增强任何形成的生物膜对抗生素敏感性的潜力。使用自动高内涵筛选共聚焦显微镜，对表达绿色荧光蛋白的临床耐甲氧西林金黄色葡萄球菌（MRSA）分离株以及无法形成多糖或蛋白质生物膜基质的同基因突变体的生物膜形成进行了定量分析。结果表明，聚乙二醇化-PDLLA涂层表现出显著的抗生物膜特性，其中M表现出最高的效果。与具有胞外多糖（PIA）生物膜基质的生物膜相比，这种抑制作用在具有蛋白质组成基质的生物膜中更强。我们的数据表明，抗生物膜作用可能是由于：（i）通过微生物表面成分识别粘附基质分子（MSCRAMMs）抑制初始附着，因为聚乙二醇通过表面水化层和空间排斥减少蛋白质表面吸附；以及（ii）由于聚合物的生物可吸收/可降解性质，随着时间的推移会发生水化和水解，从而导致微菌落的机械解体和分散。PDLLA-PEG共聚物对生物膜形态的破坏增加了对利福平和夫西地酸等抗生素的敏感性。添加1%的磺胺嘧啶银对生物膜和浮游菌都有额外的早期杀菌作用。此外，这些涂层与免疫细胞具有细胞相容性，表明它们有潜力增强细菌清除并减少钛基骨科生物材料上的细菌定植。
