Nanostructured surface modification for antimicrobial effectiveness and cytocompatibility

使用抗生素和抗菌剂的非技术性战斗感染导致了具有抗药性的“超级细菌”。另一方面，细菌不会对已知的、自然产生的抗菌肽(AMP)产生抵抗力。然而，AMP结构的复杂性排除了大量实际制备的可能性。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，从而产生了将化学物种与相反特征结合在一起的新分子“刷子”：单独使用刷毛“A”可杀死细菌和人类细胞；单独使用刷毛“B”则对细菌和人类细胞友好。令人惊讶的是，当A和B在同一个刷子里结合时，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-刷子结合到用于制造医疗器械的聚合物的表面。通过“调整”成分和加工，一条经济的途径将产生经济的“大衣”，以减少感染的发生率。妇女和代表不足的少数群体(50%)参与研究活动的同时，也实现了促进取得具有社会意义的成果的目标。技术上，这项研究的目标是定制聚合物表面，并将物理特性与生物相互作用联系起来。方法是对聚合物刷子进行表面浓缩，已独立证明聚合物刷子在模拟自然产生的抗菌肽(AMP)的溶液中具有两亲性。这些功能刷子是含有四元(或相关)侧链的共聚物，这些侧链引入电荷和细胞膜破坏，反之，引入生物相容的亲水性聚乙二醇侧链。刷子被加入到嵌段或无规共聚物中，然后作为次要组分组合成混合物。在基材聚合物上涂覆含刷子涂层的薄膜极大地改变了表面特性。用于这些研究的底物聚合物是经常用于生物医学应用的聚氨酯和有机硅。物理性能包括接触角和可获得的表面电荷密度(Zeta电位、染料吸附)。通过跨学科的合作，这些结果与与细菌和人类细胞的界面相互作用相关。这一跨学科研究为成为聚合物合成和表面科学专家的化学工程专业学生提供了更广泛的教育经验。这些学生可以在VCU医学院(抗菌药)和VCU工程与医学中心(细胞相容性)的生物安全二级实验室测试实际结果的新想法。

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).