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

细菌建造保护性的家园，与其他被称为生物膜的细菌一起生活。生物被膜会在身体的许多部位引起感染。细菌根据生活地点的不同而设计不同的生物膜。需要新的工具来联系细菌形成生物膜的位置和它们的强度，并可以帮助科学家找到破坏生物膜的新方法。这个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造的家园。这项研究将试图了解血管和血液流动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具有重要意义。该项目的另一个重点是在STEM外联方面指导研究生和本科生。研究生和本科生将在当地的科学节上教育公众研究感染的工具如何帮助创造新药。女研究生将为女本科生开设STEM职业探索工作坊。据估计，65-80%的感染是由细菌生物膜引起的。生物被膜通常对常规抗生素具有顽固性耐药或耐受性。目前细菌-宿主相互作用的动态感染模型仅限于初始细菌黏附事件或细胞内感染，不能捕捉生物膜的发展。需要新的模型来促进对宿主环境中生物被膜弹性的了解，并加速有效抗菌剂的开发。由于生物膜对微环境的变化非常敏感，因此将宿主界面结合到生物膜模型中是至关重要的。该项目的目标是设计、验证和利用体外生物膜芯片感染，该芯片可以在主机-生物膜-设备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。模型设计方面的工程进展包括控制细菌和内皮界面之间表面相互作用的微流控芯片窗口，一种常见的共培养生长介质，以及生物膜生长条件的优化，以概括具有体内特征的生物膜。验证后的模型将用于揭示血管界面如何影响生物膜结构的发展。生物膜芯片上感染也将被用来阐明静脉切应力的变化如何调节宿主-生物膜界面的生物膜力学和血管炎症反应。该项目中设计的生物膜芯片感染是第一个能够直接可视化生理条件下血管界面生物膜发展的生物膜感染模型。促进对血管界面生物膜发展的了解对于揭示宿主环境中生物膜的弹性至关重要。这一奖项反映了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。

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.