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

仿生抗菌柔性聚合物薄膜：多功能的制造、机理和集成

• 批准号: 2015292
• 负责人: Qing Cao
• 金额: $ 40万
• 依托单位: University of Illinois at Urbana-Champaign
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-15 至 2023-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2015292&HistoricalAwards=false
• 关键词: Bioinspired; Antimicrobial; Flexible; Polymer; Thin

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.

生物污染是指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一个严重问题。细菌在管道和船体表面的定植会导致严重的效率损失，从而导致更高的运营成本。对于医用植入物来说，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与血源性细菌接触的细菌粘附的首选场所。将此类感染风险降至最低的传统方法通常包括在植入物表面涂上一层缓慢释放的抗生素或杀菌剂。然而，抗生素的持续释放会导致耐药性和毒副作用。该项目的目标是开发一种新的抗菌涂层来克服这些限制。该项目的设计灵感来自蝉和蜻蜓翅膀上发现的杀菌纳米柱阵列，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独特的能力，可以通过纯粹的物理（例如导致膜破裂）相互作用杀死各种附着的细菌，而不会释放任何有害化学物质。尽管蝉和蜻蜓翅膀上的纳米柱阵列具有很好的抗菌性能，但由于它们的纳米尺度和高长宽比，模仿它们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大面积无毒抗菌涂层的实际应用能力。该项目将通过开发一种具有成本效益的方法来制备这种纳米柱阵列，这种纳米柱阵列具有独立可调的柱高、半径和间距，可以在各种具有广泛弹性性能的聚合物衬底上使用。实验和计算机模拟的结合将用于提供对杀菌机制的深入了解。这种见解与基本的工程设计原则相结合，将用于设计生物启发的抗菌膜，这些膜在杀菌功效和受影响的细菌种类数量方面可以优于天然膜。教育目标是通过利用项目中产生的外展机会和知识，培养一支可持续、适应性强、具有全球竞争力的STEM劳动力队伍。努力包括一个夏季研究项目（涉及测量收集到的蝉翅表面拓扑的显微技术培训），该项目是作为物理学青年学者计划的一部分，面向来自代表性不足群体的当地高中生，并通过开发用于生物医学应用的电子设备的多学科模块，该模块将纳入生物材料本科课程。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用于生物医学植入物的前景。这项工作的灵感来自于自然界中形成的表面，例如蝉和蜻蜓的翅膀，它们具有纳米柱状结构，可以通过纯粹的机械拉伸过程通过破裂细胞膜来杀死附着的细菌，从而提供了一种有吸引力的“无化学物质”和广谱策略来对抗细菌相关的感染和污垢。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（临界尺寸低于100纳米），这些阵列具有精确可调的柱高度、半径和间距，可以在各种具有广泛杨氏模量的聚合物基板上使用。该工艺以硅衬底为主体，采用低成本、大面积适用的纳米球光刻技术和各向异性深硅反应离子刻蚀技术，在硅衬底上制备纳米阱阵列。具有不同机械性能的聚合物的前体，然后浇铸在母体上，以产生互补的复制品。柱的高度、半径、间距和杨氏模量可以通过调整纳米球的尺寸、蚀刻时间和预聚物的选择来独立控制。制备的薄膜将通过实验和模拟相结合来阐明薄膜拓扑结构、力学性能和杀菌效果之间的详细相关性，这将为其杀菌机制提供重要的见解。第二个目标是在建模的指导下，设计纳米结构的杀菌膜，使其在更广泛的细菌谱上具有更高的杀菌功效，胜过天然的杀菌膜。该膜可以结合多种杀菌方法和功能。纳米结构的物理杀菌涂层可以制成导电的，以证明薄膜用作生物传感器电极的潜力。这种薄膜可以进一步与柔性电子元件集成，例如具有应变传感能力的惠斯通电桥，作为矫形植入物的“智能”涂层，提供长期抗菌和结构健康监测能力。该奖项反映了美国国家科学基金会的法定使命，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。