基于杂化盐响应聚合物刷构筑主动杀菌、可再生抗菌表面及相关机制研究

Antibacterial surfaces with reversibly switchable bacteria attachment, killing, and release of dead bacteria (e.g. regeneration) have been a new antibacterial strategy with great importance. In this field, how to design and develop new responsive behavior, optimize composition and structure, as well as significantly improve the antibacterial properties and elucidate the underlying mechanism have become important issues that need to be addressed urgently. To solve these problems, this project proposed a new surface which can efficiently adsorb bacteria, kill and release them in response to the change in salt concentration and/or counterion type. To this end, zwitterionic polymer brushes with strong antipolyelectrolyte effect will be first designed and synthesized via surface initiated atom transfer radical polymerization. Polyleletrolytes (bactericides) brushes then will be introduced using click chemistry, re-initiation of living radical polymerization, and combined technique of two surface-initiated living radical polymerization, based on which a series of antibacterial surfaces with various compositions and structures will be prepared. Due to the synergistic effect of the oppositely responsive behaviors of zwitterionic polymer brushes and polyelectrolyte brushes, an efficient function of bacterial attachment, killing and releasing dead bacteria in the response to salt solution can be obtained. The preparation and methodology tuning surface structure and properties, as well as the effects of polymer brush composition, type and micro-structure of the bactericides on the surface wettablility, salt-responsive behavior, and consequent antibacterial efficiency will be systematically investigated. Furthermore, the change in conformation of polymer brushes, orientation of functional groups, and surface hydration during response will be carefully characterized and studied, from which we hope to establish the relationship among surface structure, surface characteristic and the antibacterial properties. Another more important purpose of this study is to supply a comprehensive insight into the interaction between bacteria and polymer surface, and further elucidate the underlying mechanism of antibacterial effect. Therefore, we believe this project will provide a new method, significant experimental and theoretical guide to the design and preparation of new functional antibacterial surface.

具有主动吸附细菌、杀菌且可再生功能的新型抗菌表面是抗菌材料的一个重要发展方向。如何构建新的响应机制，优化结构组成，实现高效持久抗菌性能并揭示抗菌过程内在机制是该领域有待解决的重要科学问题。为此，本项目以具有强“反聚电解质效应”的两性离子聚合物为基础，通过点击化学、二次引发聚合、活性聚合联用等手段制备一系列结构组成不同的两性离子聚合物和聚电解质抗菌剂混杂分子刷体系，利用强“反聚电解质效应”和“聚电解质效应”混杂响应过程协同实现细菌吸附/脱附和杀菌功能，构筑高效持久功能抗菌表面。系统研究抗菌表面的构筑和结构调控方法，探究表面组成、结构等因素对表面性质及抗菌性能的作用规律，进一步研究杂化盐响应作用下抗菌表面链构象、电荷性质、功能基团取向及水合层性质等的变化规律，深入了解细菌与表面相互作用机理，揭示抗菌机制，建立结构-表面性质-抗菌性能关系，为功能抗菌表面的开发和应用提供理论基础和实验依据。

围绕项目研究目标，我们首先设计了一系列具有不同结构的具有有强“反聚电解质效应”的两性离子聚合物，系统研究了离子种类、阴阳离子间碳数目等结构因素对两性离子聚合物亲水性、盐响应性等性能的影响因素，揭示了盐响应作用机理，明确了实现高效盐响应作用的最佳结构设计。紧接着，以盐响应两性离子聚合物为基础，通过直接接枝抗菌剂、构建双层刷和混合刷制备了“杀菌-释放”双功能抗菌表面，研究表明，利用新型具有强“反聚电解质”效应的两性离子聚合物刷的盐响应作用，可以脱附95%以上的黏附细菌，实现表面更新，且具有优异的循环性能。针对“杀菌-释放”双功能抗菌表面细菌粘附快、需频繁再生的问题，项目进一步通过引入亲水性聚合物，通过凝胶/刷结合、混合刷和双层刷等多种结构构建了具有“长效防污-杀菌-释放”三重功能抗菌表面，与传统抗菌表面相比，改抗菌表面既能够长效抗细菌粘附，高效杀菌，又能够释放细菌实现表面再生，以polyDVBAPS/polyHEAA/TCS双层刷和混合刷为例，在对大肠杆菌120h和金黄色葡萄球菌72h的抗菌实验中，细菌吸附密度低于~106cells/cm2，杀菌率为93%以上，经1M NaCl 溶液处理后，能够释放90%以上的细菌，实现再生，经过3个循环后，其杀菌率和脱附率仍均保持在90% 以上，表现出优异的循环稳定性，具有良好的实用性。此外，利用盐响应作用，项目还构建了“聚电解质效应”和“反聚电解质效应”协同作用的双层水凝胶体系，同时发展了自发相分离一步制备双层水凝胶的方法，构建了具有盐-温度双重刺激响应的水凝胶驱动器，具有响应迅速、响应条件温和以及变形能力强等优点。通过项目研究，明晰了新型两性离子聚合物的“强反聚电解质”盐响应作用机理，并将其应用于抗菌、凝胶驱动及功能涂层的构建，研究结果对其在海洋防污、医疗器械、伤口敷料、石油钻井高盐体系助剂设计等实际应用领域具有重要的指导作用。