Liu Luting, Ercan Batur, Sun Linlin, Ziemer Katherine S, Webster Thomas J
Department of Metallurgical and Materials Engineering, Middle East Technical University, Ankara, 06800, Turkey.
Wenzhou Institute of Biomaterials and Engineering, Wenzhou Medical University, Wenzhou, China.
ACS Biomater Sci Eng. 2016 Jan 11;2(1):122-130. doi: 10.1021/acsbiomaterials.5b00431. Epub 2015 Dec 7.
Catheter-associated infections, most of which are caused by microbial biofilms, are still a serious issue in healthcare and are associated with significant morbidity, mortality, and excessive medical costs. Currently, the use of nanostructured materials, especially materials with nanofeatured topographies, which have more surface area, altered surface energy, enhanced select protein adsorption, and selectively increased desirable cell functions while simultaneously decreasing competitive cell functions, seem to be among the most promising ways for reducing initial bacteria attachment, biofilm formation, and infections. In this study, polydimethylsiloxane (PDMS), a commonly used polymeric catheter material, was formulated to mimic the nanopatterned topography of natural tissue by using a template method with nanotubular anodized titanium. Results showed that increased PDMS surface nanoscale roughness alone can inhibit both Gram-negative () and Gram-positive () bacteria adhesion and growth for up to 2 days, the time length of the current study. Additionally, increased fibroblast and endothelial cell adhesion on nano-PDMS indicated that this nanoscale topography had no toxic effects toward mammalian cells. Mechanistically, this study also developed a model for the first time to correlate bacteria responses to nanoscale roughness with initial protein and biomolecule adsorption (specifically, casein protein and glucose, which are unique biomolecules that mediate bacteria functions). Data revealed that the increase in nanoscale roughness and associated energy contributed to greater select casein adsorption during the first several minutes of culture, which is critical for decreasing bacteria attachment and growth. In contrast, no significant differences for glucose adsorption between samples before and after nanofabrication were identified. These results together indicated that the present biomimetic nanopatterned PDMS surface without any chemical or antibiotic modification has the potential to combat catheter-associated infections and should be further investigated.
导管相关感染在医疗保健领域仍然是一个严重问题，其中大部分是由微生物生物膜引起的，与显著的发病率、死亡率和过高的医疗成本相关。目前，使用纳米结构材料，特别是具有纳米特征形貌的材料，其具有更大的表面积、改变的表面能、增强的选择性蛋白质吸附，以及在选择性增加理想细胞功能的同时降低竞争性细胞功能，似乎是减少初始细菌附着、生物膜形成和感染的最有前途的方法之一。在本研究中，聚二甲基硅氧烷（PDMS）是一种常用的聚合物导管材料，通过使用纳米管阳极氧化钛的模板方法来模拟天然组织的纳米图案形貌。结果表明，仅增加PDMS表面的纳米级粗糙度就可以抑制革兰氏阴性菌（）和革兰氏阳性菌（）的粘附和生长长达2天，即本研究的时间长度。此外，纳米PDMS上成纤维细胞和内皮细胞粘附的增加表明这种纳米级形貌对哺乳动物细胞没有毒性作用。从机制上讲，本研究还首次建立了一个模型，将细菌对纳米级粗糙度的反应与初始蛋白质和生物分子吸附（具体而言，酪蛋白和葡萄糖，它们是介导细菌功能的独特生物分子）联系起来。数据显示，纳米级粗糙度和相关能量的增加导致在培养的最初几分钟内酪蛋白吸附选择性增加，这对于减少细菌附着和生长至关重要。相比之下，纳米制造前后样品之间葡萄糖吸附没有显著差异。这些结果共同表明，目前这种未经任何化学或抗生素修饰的仿生纳米图案化PDMS表面有对抗导管相关感染的潜力，应进一步研究。
