ERI: Engineering a biofilm infection-on-a-chip to elucidate the host-biofilm interface

细菌建立保护性的家园，与其他细菌一起生活，称为生物膜。 生物膜在身体的许多部位引起感染。 细菌根据它们生活的位置不同而设计不同的生物膜。 需要新的工具，可以将细菌形成生物膜的位置与它们的优势联系起来，并可以帮助科学家找到破坏生物膜的新方法。 该项目创造了新的策略来了解细菌在血管中放置的导管上建立的家园。 这项研究将试图了解血管和血流如何改变生物膜的设计和强度。该项目对于帮助创造研究和治疗血管感染的新方法非常重要。 该项目的另一个重点是指导研究生和本科生在STEM外展。 研究生和本科生将在当地的科学节上向公众介绍研究感染的工具如何帮助创造新药。 女性研究生将为女性本科生开发STEM职业探索研讨会。 据估计，细菌生物膜引起65 - 80%的感染。 生物膜通常对常规抗生素具有耐药性或耐受性。 目前细菌-宿主相互作用的动态感染模型仅限于初始细菌粘附事件或细胞内感染，并且不捕获生物膜的发展。 需要新的模型来促进对宿主环境中生物膜弹性的理解，并加速有效抗菌剂的开发。 将宿主界面纳入生物膜模型是必不可少的，因为生物膜对微环境的变化很敏感。 本项目的目标是设计、验证和利用体外生物膜感染芯片，该芯片在宿主-生物膜-器械界面的生理相关条件下有效复制中心静脉导管上的表皮葡萄球菌生物膜感染。 模型设计中的工程进展包括微流体芯片上的窗口，其控制细菌和内皮界面之间的表面相互作用，共同的共培养生长培养基，以及生物膜生长条件的优化，以重现具有体内特征的生物膜。 经验证的模型将用于揭示血管界面如何影响生物膜结构的发展。 芯片上的生物膜感染也将被用来阐明静脉剪切应力的变化如何调节生物膜力学和宿主生物膜界面处的血管炎症反应。 在该项目中设计的生物膜感染芯片是第一个生物膜感染模型，能够在生理条件下直接可视化血管界面处的生物膜发育。 推进对血管界面生物膜发展的理解对于揭示宿主环境中生物膜弹性的新观点至关重要。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。

Bacteria build protective homes to live in with other bacteria known as biofilms. Biofilms cause infections at many locations in the body. Bacteria design biofilms differently depending on the location where they live. New tools that can relate the location where bacteria form biofilms and their strengths are needed and could help scientists find new ways to destroy biofilms. This project creates new strategies to learn about the homes bacteria build on catheters placed in blood vessels. The research will seek to understand how blood vessels and blood flow change the design and strength of biofilms. The project is important for helping to create new ways to study and treat infections in blood vessels. Another focus of the project is mentoring graduate and undergraduate students in STEM outreach. Graduate and undergraduate students will educate the public about how tools for studying infections can help create new drugs at a local science festival. Women graduate students will develop STEM career exploration workshops for women undergraduate students. Bacterial biofilms are estimated to cause 65-80% of infections. Biofilms are frequently recalcitrant—resistant or tolerant—to conventional antibiotics. Current dynamic infection models of bacteria-host interactions are limited to initial bacterial adhesion events or intracellular infections and do not capture biofilm development. New models are required to advance the understanding of biofilm resilience in host environments and accelerate the development of effective antimicrobials. Incorporation of the host interface into biofilm models is essential as biofilms are sensitive to changes in microenvironment. The goal of this project is to engineer, validate, and utilize an in vitro biofilm infection-on-a-chip that effectively replicates a Staphylococcus epidermidis biofilm infection on a central venous catheter in physiologically relevant conditions at the host-biofilm-device interface. Engineering advancements in model design include a window on the microfluidic chip that controls surface interactions between bacteria and endothelial interfaces, a common co-culture growth media, and optimization of biofilm growth conditions to recapitulate biofilms with in vivo characteristics. The validated model will be used to reveal how the vascular interface influences the development of biofilm structure. The biofilm infection-on-a-chip will also be utilized to elucidate how variations in venous shear stress modulate biofilm mechanics and vascular inflammatory response at the host-biofilm interface. The biofilm infection-on-a-chip engineered in this project is the first biofilm infection model to enable direct visualization of biofilm development at the vascular interface in physiological conditions. Advancing the understanding of biofilm development at the vascular interface is critical for shedding new light on biofilm resilience in the host environment.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.