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

生物污损，即在表面堆积不需要的生物物质，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导致严重的效率损失和较高的运营成本。对于医疗植入物来说，这个问题尤其严重，因为它们的表面是细菌从伤口、手术室或设备污染物黏附的首选场所，以及手术后通过接触血源性细菌而黏附的场所。将感染风险降至最低的传统方法通常是在植入物的表面涂上一层缓慢释放的抗生素或杀生剂。然而，抗生素的持续释放可能会导致耐药性和毒副作用。该项目的目标是开发一种新型的抗菌涂料来克服这些限制。该项目的设计灵感来自蝉和蜻蜓翅膀上发现的杀菌(杀菌)纳米阵列，据信这对它们在潮湿和富含细菌的环境中的生存至关重要。这种纳米管阵列具有独特的能力，可以通过纯物理(例如，导致膜破裂)的相互作用杀死广泛范围的附着细菌，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管阵列具有诱人的抗菌性能，但由于其纳米级的尺寸和高的长宽比，模拟起来相当具有挑战性。到目前为止，制造障碍限制了充分揭示杀菌机理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，在具有广泛弹性性质的各种聚合物衬底上制备具有独立可调柱高、半径和间距的纳米管阵列。将使用实验和计算机模拟相结合的方法来深入了解杀菌机制。这一见解与基本的工程设计原则相结合，将被用于设计生物灵感抗菌膜，在杀菌效率和受影响的细菌种类数量方面，这些抗菌膜可以超过自然抗菌膜。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、适应能力强、具有全球竞争力的STEM劳动力队伍。作为物理学青年学者计划的一部分，为来自未被充分代表的群体的当地高中生开展了一个夏季研究项目(涉及测量收集到的蝉翅膀表面拓扑的微观技术培训)，并开发了一个关于生物医学应用的电子设备的多学科模块，该模块将被纳入生物材料本科课程。该项目的总体目标是显著促进生物灵感无毒和高效杀菌薄膜涂层的前景，用于生物医学植入应用。这项工作的灵感来自于自然界中形成的表面，如蝉和蜻蜓的翅膀，这些表面具有纳米柱状结构，可以通过在纯粹的机械拉伸过程中打破附着的细菌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，以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经济有效且大面积适用的方法来在各种杨氏模数范围内的聚合物衬底上制备具有精确可调柱高、半径和间距的纳米柱阵列(临界尺寸小于100 nm)。该工艺以硅衬底为母材，采用低成本、大面积适用的纳米球光刻技术，结合各向异性的深硅反应离子刻蚀技术，在硅衬底上制备纳米孔阵列阵。然后，将具有不同机械性能的聚合物的前体浇铸在母体上，以产生互补的复制品。通过调整纳米球的大小、刻蚀时间和预聚体的选择，可以独立地控制柱子的高度、半径、间距和杨氏模数。所制备的薄膜将通过实验和模拟相结合的方法来阐明薄膜的拓扑结构、力学性能和杀菌效果之间的详细关系，这将为了解其杀菌机理提供关键的见解。第二个目标是在建模的指导下，设计纳米结构杀菌膜，使其在对更广泛的细菌光谱具有更高的杀菌效率方面优于天然杀菌膜。该膜可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导电，以展示该薄膜作为生物传感器电极的潜力。这些薄膜可以进一步与灵活的电子元件集成，例如具有应变传感功能的惠斯通电桥，作为矫形植入物上的“智能”涂层，以提供长期的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智力优势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.