Rationale Design of Next Generation Antimicrobial Surfaces

生物医学设备使用者面临的一个主要问题是细菌诱发感染的风险，因为生物材料表面有利于细菌粘附和生物膜的形成。医疗设备上的生物膜占医疗保健相关感染的很大一部分，据估计，NHS每年花费约10亿英镑。生长在生物膜（一种可以生长并覆盖生物医学设备表面的黏液状物质）中的细菌对抗生素和环境的抵抗力可能比浮游细菌强数百倍。一旦细菌细胞成熟，生物膜还会将它们分散到感染部位，导致进一步的感染。这两个因素使生物膜根除成为医疗保健的一大挑战。为了解决由细菌及其生物膜引起的问题，研究人员正在采用几种不同的方法来开发“抗微生物”和“防污”表面。最常见的策略是使用涂层，释放抗生素和银离子等化学试剂来杀死细菌。然而，不幸的是，这些化学杀菌策略往往会导致抗菌素耐药性（AMR）的出现。因此，迫切需要开发不使用抗生素或其他抗菌剂杀死细菌的抗菌表面。该项目将研究在不使用化学物质的情况下开发防止生物污染的表面结构的替代方法。过去，在设计防污表面时，人们从自然中获取线索，而已知具有防污性能的自然表面被模仿的成功率有限。其中包括荷叶表面、蝉翅和壁虎皮肤等。最近，研究已经进行到开发定制纳米结构，如纳米柱，纳米锥和纳米粒子阵列。这些纳米结构的尺寸通常是任意选择的，或者与制造限制有关；而不是因为对未来细菌表面相互作用的潜在物理学的批判性理解。遗憾的是，细菌-材料表面相互作用的物理学仍然知之甚少，这极大地阻碍了下一代抗生物膜表面的创新设计。因此，本项目旨在采用实验和建模相结合的方法来解决有关结构抗菌表面如何影响细菌附着和生物膜形成的基本物理问题。该项目与EPSRC在医疗技术、生物材料、材料工程和软物质物理方面的研究成果非常一致。具体目标是：-揭示在静态和流动条件下，材料的表面物理特性如何控制细菌-材料的粘附。-开发一个强大的计算模型，以预测材料的表面物理特性和细菌的初始附着对细菌生物膜形成的影响。-开发具有长时间防污性能的新型材料表面。为了实现这些目标，将进行以下工作：-将设计和制造典型生物材料上的各种纳米结构表面。每个都将包含几种不同的纳米结构形状、大小和空间分布。-将在这些纳米结构上培养各种临床相关细菌。将进行静态和流动试验。-将使用各种光学技术分析细菌附着和生物膜的形成。-将开发一种新的内部计算模型来研究细菌和材料之间的基本物理相互作用。-使用实验结果来验证和校准计算模型。-完善计算模型，以实现对细菌附着和生物膜生长的可靠预测。-使用经过验证的模型帮助设计新型防污表面

A major issue faced by users of biomedical devices is the risk of bacteria-induced infections as biomaterial surface are favourable for bacterial adhesion and biofilm formation. Biofilms on medical devices account for a significant proportion of healthcare-associated infections that are estimated to cost the NHS approximately £1 billion per year. Bacteria that grow in biofilms, a slime-like substance that can grow and cover the surfaces of biomedical devices, can be hundreds of times more resistant to antibiotics and the environment than their planktonic counterpart. Biofilms also act to disperse additional bacterial cells into an infected site once they reach maturity, causing further infection. Both factors make biofilm eradication a great challenge for healthcare. To address the issues caused by bacteria and their biofilms, several different approaches are being taken by researchers to develop 'anti-microbial' and 'anti-fouling' surfaces. The most common strategy uses coatings that release chemical agents such as antibiotics and silver ions to kill the bacteria. Unfortunately, however, these chemical bactericidal strategies can often contribute to the emergence of antimicrobial resistance (AMR). There is, therefore, a pressing need to develop antimicrobial surfaces that do not utilise antibiotics or other antimicrobial agents to kill bacteria. This project will investigate the alternate approach of developing surface structures that prevent biofouling without the use of chemicals. In the past, cues were taken from nature when designing anti-fouling surfaces and natural surfaces known to exhibit anti-fouling behaviour were mimicked with limited success. These included the surfaces of lotus leaves, cicada wings, and gecko skin, to name but a few. More recently, research has been conducted into developing custom nanostructures such as arrays of nanopillars, nanocones, and nanopits. The sizes of these nanostructures are often chosen arbitrarily or with respect to manufacturing constraints; not as a result of a critical understanding of the underlying physics of the future bacteria-surface interaction. Regrettably, the physics of bacteria-materials surface interactions remains poorly understood, which significantly hinders the innovative design of next generation anti-biofilm surfaces.Therefore, this project aims to employ a combined experimental and modelling approach to address the fundamental physical questions about how structured antimicrobial surfaces affect bacteria attachment and biofilm formation. This project well aligns with EPSRC remits on healthcare technologies, biomaterials, materials engineering, and soft matter physics. The specific objectives are:- Reveal how the surface physical properties of materials control the bacteria-material adhesion under static and flow conditions.- Develop a robust computational model to predict the effect of surface physical properties of materials and the initial attachment of bacteria on the formation of bacterial biofilms.- Develop novel material surfaces with prolonged antifouling performance. To achieve these objectives, the following will be performed:- Various nanostructured surfaces on typical biomaterials will be designed and manufactured. Each will contain several different nanostructure shapes, sizes and spatial distributions.- Various clinically relevant bacteria will be cultured on these nanostructures. Both static and flowing tests will be carried out.- Bacterial attachment and biofilm formation will be analysed using a variety of optical techniques.- A novel in-house computational model would be developed to study the fundamental physical interactions between bacteria and materials.- Use experimental results to validate and calibrate the computational modelling. - Refine the computational models to enable robust predictions of bacterial attachment and biofilm growth.- Use the validated model to aid in the design of novel antifouling surface