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Nanostructured surface modification for antimicrobial effectiveness and cytocompatibility

$390,000FY2016MPSNSF

Virginia Commonwealth University, Richmond VA

Investigators

Abstract

Non-Technical Fighting 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. Technical The 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).

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