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.

生物污垢，即表面上不需要的生物物质的积累，是人类社会许多领域的一个严重问题，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。对于医疗植入物来说，因为它们的表面是伤口、手术室或设备污染的细菌粘附的首选部位，并且在手术后通过接触血源性细菌而将此类感染的风险降至最低的传统方法通常包括对表面进行涂层。的然而，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型抗菌涂层来克服这些限制。蝉和蜻蜓翅膀上发现的杀菌（杀菌）纳米柱阵列被认为对于它们在潮湿和细菌丰富的环境中生存至关重要，这种纳米柱阵列具有独特的杀菌能力。通过纯粹的物理（例如导致膜破裂）相互作用来附着多种细菌，而不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吸引人的抗菌特性，但由于其纳米级尺寸和特性，模仿起来相当困难。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。通过开发一种经济高效的方法，在具有各种弹性特性的各种聚合物基底上制备具有独立可调的柱高度、半径和间距的纳米柱阵列，将使用实验和计算机模拟的结合来深入了解。这种见解与基本的工程设计原理相结合，将用于设计仿生抗菌薄膜，该薄膜在杀菌功效和受影响的细菌种类数量方面优于其天然分子。通过利用该项目中产生的外展机会和知识，培养可持续、适应性强且具有全球竞争力的 STEM 劳动力。其中包括为当地高中生开展一个夏季研究项目（涉及测量收集到的蝉翅膀表面拓扑结构的微观技术培训）。作为物理学青年学者计划的一部分，来自代表性不足的群体，并通过开发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生物材料课程。该项目的总体目标是这项工作的灵感来自自然界形成的表面，例如蝉和蜻蜓的翅膀，它们具有可以杀死附着细菌的纳米柱结构。通过在纯粹的机械拉伸过程中破坏细胞膜，从而提供一种有吸引力的“无化学物质”和广谱策略来对抗细菌相关的感染和污垢。该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经济高效且大面积适用的方法来制造纳米柱阵列（临界尺寸低于 100 nm），在具有广泛杨氏模量的各种聚合物基底上具有精确可调的柱高度、半径和间距。该工艺首先以硅衬底为母体，采用低成本、大面积适用的纳米球光刻技术，结合各向异性深硅反应离子刻蚀技术，制作纳米井阵列。然后将具有不同机械性能的聚合物前体浇注到母模上，以产生互补的复制品，通过调整纳米球尺寸、蚀刻时间和所制造的预聚物的选择来独立控制柱的高度、半径、间距和杨氏模量。薄膜将用于通过实验和模拟相结合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，这将为对其杀菌能力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杀菌膜，使其在针对更广泛的细菌谱方面具有更高的杀菌功效。涂层可以导电，以证明薄膜用作生物传感器电极的潜力。薄膜可以进一步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，可提供长期抗菌和结构健康监测功能。该奖项反映了 NSF 的法定使命，并通过使用基金会的评估被认为值得支持智力价值和更广泛的影响审查标准。

项目成果

A smart coating with integrated physical antimicrobial and strain-mapping functionalities for orthopedic implants

用于骨科植入物的具有集成物理抗菌和应变映射功能的智能涂层

• DOI: 10.1126/sciadv.adg7397
• 发表时间: 2023-05-05
• 期刊: Science Advances
• 影响因子: 13.6
• 作者: Zhang, Yi;Cui, Jinsong;Chen, Kuan-Yu;Kuo, Shanny Hsuan;Sharma, Jaishree;Bhatta, Rimsha;Liu, Zheng;Ellis-Mohr, Austin;An, Fufei;Li, Jiahui;Chen, Qian;Foss, Kari D.;Wang, Hua;Li, Yumeng;McCoy, Annette M.;Lau, Gee W.;Cao, Qing
• 通讯作者: Cao, Qing