Nanostructured surface modification for antimicrobial effectiveness and cytocompatibility

用抗生素和抗菌剂对抗感染已经导致了耐药的“超级细菌”。另一方面，细菌不会对已知的天然抗菌肽（AMPs）产生耐药性。然而，AMP结构的复杂性阻碍了大批量的实际制备。其次，大多数制造“AMP模拟物”的尝试都导致了对人体细胞有毒的物质。这些瓶颈促使人们寻找类似amp的抗菌剂，从而产生了结合具有相反特征的化学物质的新型分子“刷子”：单独使用时，鬃毛“a”可以杀死细菌和人类细胞；单独使用时，猪鬃“B”对细菌和人体细胞都是友好的。令人惊讶的是，当A和B组合在同一把刷子上时，A-刷毛只杀死细菌，而B-刷毛“保护”人类细胞。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”成分和加工，经济的途径将产生经济的“外套”，以减少感染的发生率。妇女和代表性不足的少数群体（50%）参与研究活动的另一个目标是促进实现与社会相关的成果。技术本研究的目的是裁剪聚合物表面和物理性质与生物相互作用的相关性。该方法是聚合物刷的表面浓度，其已独立显示在模拟天然抗菌肽（AMPs）的溶液中具有两亲性。这些功能刷是共聚物，含有引入电荷和破坏细胞膜的四元（或相关）侧链，相反，具有生物相容性的亲水性聚乙二醇侧链。刷并入分段或随机共聚物，然后组合成共混物作为次要成分。在基材聚合物上的含刷涂层薄膜极大地改变了表面特性。这些研究的基质聚合物是聚氨酯和有机硅，它们经常用于生物医学应用。物理性质包括接触角和可接触表面电荷密度（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拓宽教育经验，使他们成为聚合物合成和表面科学方面的专家。这些学生可以在VCU医学院（抗菌剂）和VCU工程与医学中心（细胞相容性）的生物安全二级实验室中测试新想法的实际结果。

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).