Bioinspired Antimicrobial Flexible Polymer Thin Films: Fabrication, Mechanism, and Integration for Multi-Functionality

生物结垢，即不需要的生物物质在表面上的积累，是人类社会许多部门的严重问题。细菌在管道和船体表面上的定殖导致严重的效率损失，从而导致更高的运行成本。对于医疗植入物来说，这个问题尤其严重，因为它们的表面是伤口、手术室或设备污染以及术后通过接触血源性细菌而粘附细菌的首选部位。 最大限度地减少此类感染风险的常规方法通常涉及用一层缓慢释放的抗生素或杀生物剂涂覆植入物的表面。然而，抗生素的持续释放可导致耐药性和毒副作用。本项目的目标是开发一种新型抗菌涂层来克服这些限制。该项目的设计灵感来自于在昆虫和昆虫翅膀上发现的杀菌（杀死细菌）纳米柱阵列，这被认为是它们在潮湿和细菌丰富的环境中生存的关键。这种纳米柱阵列具有通过纯粹的物理（例如膜破裂引起的）相互作用杀死广谱附着细菌的独特能力，而不释放任何有害化学物质。尽管它们具有吸引人的抗菌性能，但由于它们的纳米尺度尺寸和它们的高长宽比，在翼片和翼片上的纳米柱阵列是相当具有挑战性的。 迄今为止，制造障碍限制了充分揭示杀菌机制或生产用于实际应用的大面积无毒抗菌涂层的能力。该项目将通过开发一种具有成本效益的方法来克服这些障碍，以在具有广泛弹性特性的各种聚合物基底上制备这种纳米柱阵列，具有独立可调的柱高度，半径和间距。结合实验和计算机模拟将被用来提供深入了解杀菌机制。 这种见解，结合基本的工程设计原则，将用于设计生物启发的抗菌膜，可以在杀菌效果和受影响的细菌物种数量方面优于天然抗菌膜。 教育目标是通过利用项目中产生的外联机会和知识，培养可持续，适应性强和具有全球竞争力的STEM劳动力。努力包括一个夏季研究项目（包括测量收集的翅膀表面拓扑结构的显微技术培训），作为物理学青年学者计划的一部分，为来自代表性不足群体的当地高中学生提供培训，并开发一个关于生物医学应用电子设备的多学科模块，该模块将纳入本科生课程，该项目的总体目标是显著推进生物启发无毒和高效杀菌薄膜涂层在生物医学植入物应用中的前景。 这项工作的灵感来自于自然界中形成的表面，例如具有纳米柱撑结构的螺旋桨和螺旋桨，这些结构可以通过在纯粹的机械拉伸过程中破坏细胞膜来杀死附着的细菌，从而提供了一种有吸引力的“无化学品”和广谱策略来对抗细菌相关的感染和污染。 这一目标将通过实现两个具体目标来实现。 第一个目标是开发一种具有成本效益和大面积适用的方法来制造纳米柱阵列（具有亚100 nm的临界尺寸），其具有精确可调的柱高度，半径和各种聚合物基底上的间距，具有广泛的杨氏模量。该工艺从在作为母版的Si衬底上制造单胞阵列开始，使用低成本和大面积适用的纳米球光刻以及各向异性深Si反应离子蚀刻。然后将具有不同机械性能的聚合物前体浇铸在母版上以产生互补的复制品。柱的高度，半径，间距和杨氏模量独立地控制通过调整纳米球的大小，蚀刻时间，和预聚物的选择。 通过实验和模拟相结合的方法，将使用所制造的薄膜来阐明薄膜拓扑结构、机械性能和杀菌功效之间的详细相关性，这将为其杀菌机制提供关键的见解。 第二个目标是设计纳米结构的杀菌膜，在建模的指导下，在对更广泛的细菌谱的更高杀菌功效方面优于它们的天然对应物。 这些薄膜可以与多种杀菌方法和功能相结合。 纳米结构的物理杀菌涂层可以制成导电的，以证明该膜用作生物传感器电极的潜力。 该薄膜还可以与柔性电子元件集成，例如具有应变传感功能的惠斯通电桥，作为骨科植入物上的“智能”涂层，提供长期抗菌和结构健康监测能力。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Biofouling, the accumulation of unwanted biological matter on surfaces, is a serious problem in many sectors of human society. The colonization of bacteria on the surfaces of pipelines and ship hulls leads to severe efficiency loss and thus higher operating cost. The problem is especially severe for medical implants, as their surfaces are preferred sites for the adhesion of bacteria from wound, operating room, or equipment contaminations, and post-operatively via contact with bloodborne bacteria. The conventional approach to minimize the risk of such infections typically involves coating the surface of the implants with a layer of slowly releasing antibiotics or biocides. However, the sustained release of antibiotics can lead to drug resistance and toxic side effects. The goal of this project is to develop a novel antimicrobial coating to overcome these limitations. The project’s design is inspired by the bactericidal (bacteria killing) nanopillar arrays identified on cicada and dragonfly wings, which are believed to be crucial for their survival in humid and bacteria-rich environments. Such nanopillar arrays have the unique capability to kill a wide spectrum of attached bacteria through purely physical (e.g. membrane rupture causing) interactions, without releasing any harmful chemicals. Despite their attractive antimicrobial properties, the nanopillar arrays on cicada and dragonfly wings are quite challenging to mimic due to their nanometer-scale dimensions and their high length to width ratios. To date, fabrication obstacles have limited the capability to fully reveal the bactericidal mechanism or to produce large-area nontoxic antimicrobial coatings for practical applications. This project will overcome these obstacles by developing a cost-effective approach to prepare such nanopillar arrays, with independently adjustable pillar height, radius, and spacing, on various polymer substrates with a wide range of elastic properties. A combination of experiments and computer simulations will be used to provide insight into the bactericidal mechanism. This insight, combined with fundamental engineering-design principles, will be used to design bioinspired antimicrobial films that can outperform their natural counterparts in terms of bactericidal efficacy and the number of bacteria species affected. The educational goal is to prepare a sustainable, adaptable, and globally competitive STEM workforce by exploiting the outreach opportunities and knowledge generated in the project. Efforts include a summer research project (involving training in microscopic techniques for measuring the surface topology of collected cicada wings) for local high-school students from underrepresented groups as part of the PhYSics Young Scholars program and by developing a multidisciplinary module on electronic devices for biomedical applications that will be incorporated into an undergraduate-level course on biomaterials.The overarching objective of this project is to significantly advance the prospect of bioinspired non-toxic and high-efficiently bactericidal thin-film coatings for biomedical implant applications. The work is inspired by surfaces formed in nature, such as cicada and dragonfly wings, that have nano pillared structures that can kill attached bacteria through rupturing their cell membranes in a purely mechanical stretching process, and thus offer an attractive “chemical-free” and wide-spectrum strategy to fight against bacteria-related infections and fouling. The objective will be achieved by fulfilling two specific goals. The FIRST Goal is to develop a cost-effective and large-area applicable approach to fabricate nanopillar arrays (with sub-100 nm critical dimensions) with precisely adjustable pillar height, radius, and spacing on various polymer substrates with a wide range of Young’s moduli. The process starts from the fabrication of nanowell arrays on a Si substrate as the master, using low cost and large-area-applicable nanosphere lithography together with the anisotropic deep Si reactive-ion etching. Precursors of polymers with different mechanical properties are then casted against the master to yield the complementary replicas. Pillar height, radius, spacing, and the Young’s modulus are controlled independently by adjusting the nanosphere size, the etching time, and the choice of prepolymers. The fabricated films will be used to elucidate the detailed correlation between the film topology, mechanical properties and bactericidal efficacy through a combination of experiment and simulation, which will provide critical insight into their bactericidal mechanism. The SECOND Goal is to engineer nanostructured bactericidal films, as guided by modeling, to outperform their natural counterparts in terms of higher bactericidal efficacy against a broader bacterial spectrum. The films can be combined with multiple bactericidal approaches and functionalities. The nanostructured physical bactericidal coats can be made electrically conductive to demonstrate the potential for the films to be used as electrodes for biosensors. The films can be further integrated with flexible electronic components, e.g. a Wheatstone bridge with strain-sensing capabilities, as “smart” coatings on orthopedic implants to provide both long-term antibacterial and structure-health monitoring capabilities.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.