CAREER: Mechanical Mechanisms of Biofilm Survival on Implant Surfaces

Implant infection is one of the most frequent and severe complications associated with the use of synthetic materials in the human body. Implant devices account for approximately one-fourth of hospitalacquired infections (Magill 2014). Bacterial adhesion is the first step of device-related infections, and biofilm formation decreases the likelihood of successful disease resolution by antibiotic treatment. When compared to planktonic (free floating) bacteria, bacteria in biofilms require up to 1000x higher antibiotic dose. Further, the dense and complex matrix of biofilms typically limits antibiotic access (diffusion confinement) and is also directly related to biofilm mechanics (deformability). Mechanical properties such as adhesion, deformability, and diffusion confinement make biofilm-related infections difficult to understand, treat, and resolve. For this reason, characterizing the role of biofilm mechanics (e.g., adhesion, deformability, diffusion confinement) is crucial in evaluating the safety of medical devices and understanding disease progression at these interfaces. The goal of this CAREER proposal is to advance the basic understanding of biofilms formed on device surfaces through innovative quantitative methods for measurement of biofilm adhesion and deformability. Adhesion and deformability will provide new knowledge towards a comprehensive understanding of the role that biofilm mechanics play in medical device infections. The field of mechanics is primarily concerned with how materials interact with forces. In the first objective, the focus is on assessing how much force is required to overcome biofilm adhesion and what surface factors control the level of force required. In the second objective, the focus is how the biofilm responds to forces that compress the biofilm and the underlying architecture that provides the structural integrity to resist deformation. Intellectual Merit: This proposal harnesses experimental thin film mechanics to address an imminent biological adhesion challenge. To critically assess the contribution of biofilm mechanics on device infections, this project will 1) extract 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) explore new relationships between antibiotic resistance and biofilm deformability, and 3) generate 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 provides new target values with which to engineer implant surfaces. These contributions will enable advances in engineering of medical implant devices. This project will be the first use of the laser spallation technique to compare the adhesion strength of biofilms to mammalian cells, which will lead directly to the systematic study of biomaterial to medical device surface combinations. This project will harness unique thin film expertise and capabilities to provide new insight into biofilm structure-function relationships and relate these to effective antibiotic dosages and environmental cues. Broader Impacts Decreasing the occurrence of medical device infections would improve quality of life for the quarter of a million Americans who experience device infections each year. A fundamental understanding of bacterial biofilm mechanics at these interfaces and establishment of improved biocompatibility criteria based on new Adhesion Index will decrease the likelihood for strong biofilm adhesion to form. Thus, we expect a reduction in medical device infections to occur. Beyond the laboratory, our educational goals are to impact society more broadly through educator development, increased public science literacy, and development of a diverse STEM workforce at the intersection of engineering and medicine. In collaboration with the FDA, this project will provide training in biocompatibility screening technology and non-traditional career paths for mechanical engineers. Community engagement activities are planned to increase public science literacy. This project 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 feedback across the network.