Slippery Nanoemulsion-Infused Polymer Coatings that Prevent Bacterial Fouling and Block Bacterial Virulence

项目摘要：这个R21项目将开发新的合成液体注入表面和 在临床和医疗环境中防止细菌污染和减弱细菌毒性的涂料。 这些目标将通过追求两个重点和综合目标来实现：(1)探索新的 注入纳米乳液的光滑多孔表面(SNIP)的设计和表征注入的影响 纳米乳液对防污行为的影响，包括防止细菌病原体污染的能力，以及(2) 设计能够容纳和释放活性物质的夹子，并表征药物洗脱夹子的能力 加强对表面生物污染的预防，减轻细菌负荷和毒力。 细菌对表面的污染和污染在许多工业领域构成持续且代价高昂的威胁， 商业和临床医疗保健环境。这些问题迫在眉睫，潜在的社会和 预防细菌污染和毒力的战略的经济影响几乎不可能被夸大。 许多策略被用来设计抗细菌污染的材料，但它们最终都失败了。 当部署在真实世界场景中时。从根本上说，防污或防污设计的新方法 超越传统设计策略的毒性表面是迫切需要的，并将具有 对人类健康有重大影响。 防止表面细菌污垢的一种有希望的方法是利用“滑”的特性。 注入液体的多孔表面。这些所谓的‘SLIPS’在医疗保健环境中具有巨大的潜力，但 通常是被动的材料--它们可以强烈地排斥它们所接触的细菌，但也可以 几乎不能减弱周围环境中生物体的毒力行为或减少微生物负荷。 这项提案旨在推进“药物洗脱”单据的创新设计，以应对这一挑战， 因此，通过洗脱抗菌剂和抗毒剂来增强固有的抗生物污垢性能。 拟议的工作基于两个广泛的主张：(I)注入油包水纳米乳液， 而不是传统的疏水油，变成多孔的聚合物涂层可以用来设计“滑” 可容纳和释放生物活性物质的防污材料(SNIPS)，以及(Ii)含有有效成分的剪刀 抗生素和新型抗菌剂可以减少细菌载量，改变细菌行为，从而 增强固有的抗生物污垢性能，扩大注液材料的实用价值。我们的 创新和跨学科研究计划寻求探索这些新想法并测试假设，这些假设将 为新型合成聚合物涂料的开发奠定了基础，这种涂料可以防止细菌污染 实用的环境。拟议研究的范围体现了新的问题和相关的风险水平。 适合于R21级别的研究，并联合了一支成熟的、积极合作的团队 研究人员演示和探索这种以材料为重点的新方法的可行性。

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.