Rationale Design of Next Generation Antimicrobial Surfaces

生物医疗设备使用者面临的一个主要问题是细菌引起感染的风险，因为生物材料表面有利于细菌黏附和生物膜的形成。医疗器械上的生物膜在医疗保健相关感染中占很大比例，据估计，这些感染每年给NHS造成的损失约为10亿GB。在生物膜中生长的细菌对抗生素和环境的抵抗力可能是浮游生物细菌的数百倍。生物膜是一种黏液状物质，可以生长并覆盖生物医疗设备的表面。生物膜一旦成熟，也会将更多的细菌细胞分散到感染部位，导致进一步感染。这两个因素使得根除生物膜对医疗保健来说是一个巨大的挑战。为了解决细菌及其生物膜造成的问题，研究人员正在采取几种不同的方法来开发“抗微生物”和“防污染”表面。最常见的策略是使用涂层来释放抗生素和银离子等化学试剂来杀灭细菌。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来杀灭细菌的抗菌表面。该项目将研究另一种方法，即在不使用化学品的情况下开发防止生物污垢的表面结构。在过去，在设计防污表面时，从自然中获取线索，而已知的具有防污行为的自然表面被模仿，但成功有限。其中包括荷叶的表面、蝉的翅膀和壁虎的皮肤，仅举几例。最近，研究人员一直在开发定制的纳米结构，如纳米柱阵列、纳米锥体和纳米坑。这些纳米结构的大小通常是随意选择的，或者是根据制造限制而选择的；而不是因为对未来细菌-表面相互作用的基本物理的关键理解的结果。遗憾的是，细菌-材料表面相互作用的物理机制仍然知之甚少，这严重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结构化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在医疗保健技术、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：-揭示材料表面物理性质如何在静态和流动条件下控制细菌-材料黏附。-开发一个稳健的计算模型，以预测材料表面物理性质和细菌的初始附着对细菌生物膜形成的影响。-开发具有持久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。-各种临床相关的细菌将在这些纳米结构上培养。将进行静态和流动测试。-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，以研究细菌与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。-改进计算模型，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来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