Nanostructured surface modification for antimicrobial effectiveness and cytocompatibility

纳米结构表面改性可提高抗菌效果和细胞相容性

• 批准号: 1608022
• 负责人: Kenneth Wynne
• 金额: $ 39万
• 依托单位: Virginia Commonwealth University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1608022&HistoricalAwards=false
• 关键词: Nanostructured; surface; modification; antimicrobial; effectiveness

Non-TechnicalFighting infections with antibiotics and antimicrobials has led to resistant "super bugs". On the other hand, bacteria do not build up resistance to long-known, naturally occurring antimicrobial peptides (AMPs). However, AMP structural complexity precludes practical preparation of large quantities. Secondly, most attempts to make "AMP mimics" have resulted in materials that are toxic to human cells. These bottlenecks prompted a search for AMP-like antimicrobials that led to new molecular "brushes" combining chemical species with opposite characteristics: alone, bristle "A" kills both bacteria and human cells; alone, bristle "B" is friendly to bacteria and human cells. Surprisingly, when A and B are combined in the same brush, A-bristles killed only bacteria and B- bristles "protected" human cells. Going forward, research is aimed at incorporating these AB-brushes into the surface of polymers used to make medical devices. By "tuning" composition and processing, an economical pathway will result in economical "overcoats" for reducing the incidence of infections. Participation of women and underrepresented minorities (50%) in research activities follows a parallel goal of contributing to achievement of societally relevant outcomes. TechnicalThe objective of this research is tailoring polymer surfaces and correlation of physical properties with bio-interactions. The approach is surface concentration of polymer brushes, which have been independently shown to have amphiphilic character in solution that mimics naturally occurring antimicrobial peptides (AMPs). These functional brushes are copolymers containing quaternary (or related) side chains that introduce charge and cell membrane disruption and, conversely, hydrophilic polyethylene glycol side chains that are biocompatible. Brushes are incorporated into segmented or random copolymers followed by combination into blends as a minor component. Thin films of brush-containing overcoats on substrate polymers greatly change surfaces characteristics. Substrate polymers for these investigations are polyurethanes and silicones, which are often used in biomedical applications. Physical properties include contact angles and accessible surface charge density (zeta potentials, dye adsorption). Through interdisciplinary collaborations these results are correlated with interfacial interactions with bacteria and human cells. This interdisciplinary research provides a broadening educational experience for chemical engineering students who become experts in polymer synthesis and surface science. These students get to test new ideas for real outcomes in a biosafety level 2 laboratory in the VCU School of Medicine (antimicrobials) and the VCU Center for Engineering and Medicine (cytocompatibility).

用抗生素和抗菌剂对抗感染导致了耐药的“超级细菌”。另一方面，细菌不会对长期已知的天然存在的抗菌肽（AMP）产生耐药性。然而，AMP结构的复杂性排除了大量的实际制备。其次，大多数制造“AMP模拟物”的尝试都导致了对人类细胞有毒的材料。这些瓶颈促使人们寻找类似AMP的抗菌剂，从而产生了新的分子“刷子”，将具有相反特性的化学物质结合在一起：单独的刚毛“A”既杀死细菌又杀死人体细胞;单独的刚毛“B”对细菌和人体细胞友好。令人惊讶的是，当A和B组合在同一把刷子中时，A-刷毛只杀死细菌，而B-刷毛“保护”人体细胞。展望未来，研究的目标是将这些AB刷结合到用于制造医疗设备的聚合物表面。通过“调整”组合物和加工，经济的途径将产生用于降低感染发生率的经济的“外套”。妇女和代表性不足的少数民族（50%）参与研究活动遵循的一个平行目标是促进实现与社会相关的成果。技术本研究的目的是剪裁聚合物表面和物理性质与生物相互作用的相关性。该方法是表面浓度的聚合物刷，这已被独立地证明具有两亲性的字符在溶液中，模仿天然存在的抗菌肽（AMP）。这些功能刷是含有引入电荷和细胞膜破坏的季铵（或相关）侧链的共聚物，并且相反，含有生物相容的亲水性聚乙二醇侧链。刷被并入到嵌段或无规共聚物中，然后作为次要组分组合成共混物。在基材聚合物上的含刷的外涂层薄膜极大地改变了表面特性。用于这些研究的基质聚合物是聚氨酯和有机硅，它们通常用于生物医学应用。物理性质包括接触角和可接近的表面电荷密度（zeta电位，染料吸附）。通过跨学科合作，这些结果与细菌和人类细胞的界面相互作用相关。这项跨学科的研究为化学工程专业的学生提供了更广泛的教育经验，他们将成为聚合物合成和表面科学的专家。这些学生可以在VCU医学院（抗菌剂）和VCU工程和医学中心（细胞相容性）的生物安全2级实验室中测试新想法的真实的结果。