PROJECT SUMMARY: This R21 project will develop new classes of synthetic liquid-infused surfaces and coatings that prevent bacterial fouling and attenuate bacterial virulence in clinical and healthcare settings. These objectives will be accomplished by the pursuit of two focused and integrated Aims: (1) to explore new designs of slippery nanoemulsion-infused porous surfaces (SNIPS) and characterize the impacts of infused nanoemulsions on antifouling behavior, including the ability to prevent fouling by bacterial pathogens, and (2) to design SNIPS that can host and release active agents and characterize the ability of drug-eluting SNIPS to enhance prevention of surface biofouling and attenuate bacterial load and virulence. Contamination and fouling of surfaces by bacteria pose persistent and costly threats in many industrial, commercial, and clinical healthcare settings. These problems are urgent, and the potential societal and economic impacts of strategies 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. One promising approach to prevent bacterial fouling on surfaces is to exploit the properties of `slippery' liquid-infused porous surfaces. These so-called `SLIPS' have enormous potential in healthcare settings, but are generally passive materials—they can strongly repel bacteria with which they come into contact, but can do little to attenuate the virulent behaviors of organisms in surrounding environments or reduce microbial load. This proposal seeks to advance innovative designs of `drug-eluting' SLIPS that can address this challenge and, thereby, enhance inherent anti-biofouling properties by eluting antimicrobial and anti-virulence agents. The proposed work is based on two broad propositions: (i) that infusion of water-in-oil nanoemulsions, rather than conventional hydrophobic oils, into porous polymer coatings can be used to design `slippery' antifouling materials (`SNIPS') that can host and release bioactive agents, and (ii) that SNIPS containing potent antibiotics and novel anti-virulence agents can reduce bacterial loads and alter bacterial behaviors in ways that enhance inherent anti-biofouling behaviors and expand the practical utility of liquid-infused materials. Our innovative and cross-disciplinary research plan seeks to explore these new ideas and test hypotheses that will create a foundation for the development of new synthetic polymer coatings that can prevent bacterial fouling in practical settings. The scope of the proposed studies embodies novel questions and associated levels of risk that are appropriate for an R21-level study and unites a team of established and actively collaborating investigators to demonstrate and explore the feasibility of this new materials-focused approach.

PROJECT NARRATIVE / RELEVANCE Contamination and fouling of surfaces by bacteria is a critical problem in many healthcare settings and can lead to serious and substantial burdens that are costly in economic and human terms. Many materials have been designed to resist bacterial fouling, but all of these strategies ultimately fail when deployed in real-world scenarios or for extended periods. Fundamentally new approaches to the design of robust antifouling surfaces and coatings that move beyond conventional materials design strategies are desperately needed, would have substantial impacts on human health, and are the focus of this project.