CAREER: Mechanical Mechanisms of Biofilm Survival on Implant Surfaces

这个学院早期职业发展（Career）奖将探索细菌生物膜力学在美国人每年经历的25万医疗器械感染中所起的作用。研究成果将包括：(1)对细菌生物膜力学的基本理解；(2)建立改进的生物相容性标准。这些知识最终将用于减少医疗器械感染。这项工作产生的新的生物膜力学知识将为控制生物膜的积累和扩散提供信息。因此，研究成果也将影响到医药以外的许多行业，包括海事、食品、水、石油、造纸、航空航天等行业。在实验室之外，这项工作将通过pi设计的倡议“牛顿团队”培养工程和医学交叉领域的多元化劳动力。Newton的团队将为高等教育中的力学教师提供新的动手主动学习活动，以减少感知到的实施障碍。来自各种机构（研究密集型，主要是本科生，工程重点，公立和私立，西班牙裔服务机构，以及历史上的黑人学院和大学）的教师将参与该项目，将新的学习活动纳入他们的课堂，并通过网络提供他们的教育见解。这项工作利用实验薄膜力学来研究迫在眉睫的生物粘附挑战。研究活动将通过三种方式批判性地评估生物膜力学对设备感染的影响：(1)通过提取促进强生物膜粘附的主要参数，这将有助于建立新的粘附指数-哺乳动物细胞粘附与生物膜粘附的比率，(2)通过探索生物膜的可变形性，以及(3)通过生成关于生物膜网格尺寸的新信息。有了这些知识，药理学领域可以更准确地构建与下一代药物运载工具相关的扩散模型，这些运载工具被设计为通过生物膜等受限网络进行机动。此外，粘附指数将为设计种植体表面提供新的目标值。项目创新源于通过一系列先进的表征技术来探测生物膜积累的新方法，这些技术包括激光散裂，激光共聚焦扫描显微镜和原子力显微镜的结合，以及粒子迁移率分析。这些贡献将阐明力学（粘附，变形，约束）在生物膜感知威胁级别中的作用，这将使PI在应用力学方面建立自己的职业生涯。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。

This Faculty Early Career Development (CAREER) award will explore the role that bacterial biofilm mechanics play in the quarter of a million medical device infections experienced by Americans each year. Research outcomes will include: (1) a fundamental understanding of bacterial biofilm mechanics and (2) establishment of improved biocompatibility criteria. This knowledge will ultimately be used to reduce medical device infections. The new biofilm mechanics knowledge produced by this work will inform the ability to control biofilm accumulation and dispersal. Therefore, the research outcomes will also impact many industries beyond medicine including the maritime, food, water, oil, paper, and aerospace industries. Beyond the laboratory, this work will cultivate a diverse workforce at the intersection of engineering and medicine through a PI-designed initiative, “Newton’s Team”. Newton’s Team will equip mechanics instructors in higher education with new hands-on active learning activities that reduce perceived implementation barriers. Faculty from a wide variety of institutions (research intensive, primarily undergraduate, engineering focused, public and private, Hispanic-serving institutions, and Historically Black Colleges and Universities) will participate in the project by incorporating the new learning activities into their classrooms and providing their educational insights across the network.This work harnesses experimental thin film mechanics to investigate an imminent biological adhesion challenge. Research activities will critically assess the influence of biofilm mechanics on device infections in three ways: (1) by extracting the dominant parameters that promote strong biofilm adhesion, which will aid in establishing a novel Adhesion Index – a ratio of mammalian cell adhesion to biofilm adhesion, (2) by exploring biofilm deformability, and (3) by generating new information on the mesh size of biofilms. Armed with this knowledge, the field of pharmacology can more accurately construct diffusion models relevant for next generation drug delivery vehicles designed to maneuver through confined networks like biofilms. Additionally, the Adhesion Index will provide new target values with which to engineer implant surfaces. Project innovation stems from new approaches to probe biofilm accumulation through a suite of advanced characterization techniques which include laser spallation, combined confocal laser scanning microscopy and atomic force microscopy, and particle mobility assays. These contributions will elucidate the role of mechanics (adhesion, deformation, confinement) in the perceived threat level of a biofilm, which will allow the PI to establish her career in applied mechanics.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.