Slippery Liquid-Infused Polymer Coatings that Release Hydrophilic Antimicrobial Agents - PROJECT SUMMARY: This R21 project will develop new classes of synthetic liquid-infused porous surfaces (or `SLIPS') that address challenges related to bacterial fouling and virulence in clinical and healthcare settings. Our objectives will be accomplished by the pursuit of two focused and synergistic Aims: (1) to explore designs of novel drug-patterned `proto-SLIPS' that can release potent and highly water-soluble antibiotics and thereby reduce biofouling and bacterial load, and (2) to explore new designs of `proto-SLIPS' that release synthetic anti-virulence agents that can block bacterial communication and attenuate virulent behaviors. Colonization and fouling of surfaces by bacteria pose persistent and costly threats to human health. These problems are urgent, and the potential societal and economic impacts of robust methods to prevent bacterial fouling and virulence are nearly impossible to overstate. Many strategies have been used to design materials that resist bacterial fouling, but all of them ultimately fail when deployed in real-world scenarios. Fundamentally new approaches to the design of antifouling or `anti-virulence' surfaces that move beyond conventional design strategies are desperately needed and would have substantial impacts on human health and well-being. One promising approach to prevent bacterial fouling is to exploit the inherent anti-biofouling properties of polymer-based SLIPS coatings. These liquid-infused coatings have enormous potential in healthcare settings, but are generally passive materials—i.e., they can strongly repel bacteria with which they come into contact, but cannot reduce microbial load or attenuate the virulent behaviors of organisms in surrounding environments. This proposal seeks to advance innovative new designs of `drug-eluting' SLIPS that can address this challenge and enhance inherent anti-biofouling properties by releasing either antimicrobial or anti-virulence agents. The proposed work is based on our recent and unexpected discovery that the infusion of hydrophobic oils into porous polymer coatings patterned with small spots of a potent and highly water-soluble antibiotic leads to drug-patterned `proto-SLIPS' that can (i) release antibiotic into aqueous environments and, subsequently, (ii) transform or self-heal into SLIPS coatings that are uniformly slippery and strongly antifouling to pathogenic bacteria. This approach is unprecedented, conceptually simple, and has potential to lead to innovative polymer coatings that can both strongly prevent surface biofouling (via inherent slippery character) and reduce bacterial load or alter bacterial behavior in ways that could advance the application of SLIPS in healthcare contexts (e.g., to prevent fouling or infection on or around interventional devices). Our cross-disciplinary research plan seeks to explore these new ideas and test hypotheses to create a foundation for the design of new synthetic polymer coatings with superior anti-biofouling properties. The proposed studies embody novel questions and associated levels of risk and reward appropriate for an R21-level study and unite a team of established and actively collaborating investigators to demonstrate and explore the feasibility of this new approach.
