Chair of Ph.D. Committee, Jessica Schiffman
The emergence and spread of antibiotic resistance across microbial species necessitates the need for alternative approaches to mitigate the risk of infection without relying on commercial antibiotics. Biofilm-related infections are a class of notoriously difficult to treat healthcare-associated infections that frequently develop on the surface of implanted medical devices. As biofilm formation is a surface-associated phenomenon, understanding how the intrinsic properties of materials affect bacterial adhesion enables the development of structure-property relationships that can guide the future design of infection-resistant materials. Despite lacking visual, auditory, and olfactory perception, bacteria still manage to sense and attach to surfaces. It has previously been reported that bacteria can detect and differentiate the surface chemistry and topography of surfaces. However, the influence of the stiffness and thickness on bacterial-surface interactions is relatively unknown. In this thesis, we will investigate the effect that the fundamental material properties of polymer films and hydrogels (chemistry, stiffness, and thickness) have on bacterial adhesion and the surface-associated transport of bacteria. By tuning the mechanical properties of two chemically distinct hydrogels, poly(ethylene glycol) and agar, we determined that, independent of hydrogel chemistry and incubation time, Escherichia coli and Staphylococcus aureus attachment correlated positively to increasing hydrogel stiffness. Dynamic shear flow studies demonstrated the importance of substrate stiffness on Staphylococcus aureus surface-associated transport, as the stiffness was found to influence the length and frequency of Staphylococcus aureus dynamic adhesion to poly(ethylene glycol) surfaces (brushes and hydrogels). To further explore the effect that hydrogel stiffness has on bacterial adhesion, we investigated the effect of hydrogel thickness, which elucidated a new depth-dependent component to bacterial adhesion. On 100 μm thick hydrogels, the adhesion of Escherichia coli and Staphylococcus aureus correlated positively with hydrogel stiffness, whereas on 10 μm thin hydrogels, a substantially greater adhesion was displayed. By decoupling the effect of stiffness and thickness from hydrogel chemistry, we unlocked specific structure-property relationships that can be tailored to control the degree of bacterial adhesion and subsequently biofilm formation. In the final portion of the talk, the development and characterization of a universal surface modification that repels microbes will be discussed. This platform can synergistically enhance the antifouling performance of covalently crosslinked poly(ethylene glycol) and physically crosslinked agar hydrogels through the robust and facile incorporation of a fouling-resistant polymer zwitterion, poly(2-methacryloyloxyethyl phosphorylcholine). Dopamine polymerization was initiated while swelling the hydrogel, which provided an osmotic driving force into the hydrogel interior. The incorporation of the zwitterion supplemented the fouling-resistance of both hydrogels without altering their mechanical properties. If viewed together, the structure-property relationships and complementary fouling-resistant zwitterionic chemistry developed in this work offer alternative approaches to mitigate the risk of bacterial infections without relying on antibiotics.