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

Worcester Polytechnic Institute, Worcester MA

Investigators

Abstract

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.