Temperature and pH-Responsive Layer-by-Layer Coatings for the Prevention of Bacterial Colonization

Abstract

All biomaterials are prone to bacterial adhesion that can further lead to the development of biofilms, which are colonies of bacteria surrounded by extracellular polymeric substances that are notoriously difficult to treat. As a method to pre-emptively prevent biofilm formation, this dissertation research has focused on understanding how to create stimuli-responsive, layer-by-layer (LbL) polymer films that can controllably release antibiotics during the early stages of bacterial adhesion. Two complementary strategies have been explored for sequestering antibiotics in polymer films, namely (1) temperature-responsive micellar containers, which can trap hydrophobic small molecules, and (2) pH-responsive assemblies, which utilize changes in polymer ionization to uptake and release cationic small molecules. Recognizing that biomaterials often have complicated 3D structures, the LbL technique was chosen for constructing antimicrobial-hosting coatings as it enables uniform deposit on a variety of substrates and easily tunable antibiotic payload. My goal was to relate stimuli-responsive behavior of polymers in LbL films to their ability to selectively trigger release of small molecules and to establish methods to maximize antibiotic uptake while minimizing uncontrollably release, with a focus on preventing leaching at physiological pH (pH 7.5). Leaching antibiotics in normal physiological conditions is particularly undesirable as the presence of low levels of antibiotics has been shown to increase the chance for bacteria to develop resistance to that antibiotic. This goal was accomplished by studying the physicochemical characteristics of LbL coatings and correlating them with their antibiotic content and release profiles. My findings widen the fundamental knowledge about the functionality of temperature- responsive micelles in LbL coatings and open the door to creating biocompatible LbL coatings via direct polymer assembly with antibiotics. Moreover, these results can be useful guidelines for designing antibiotic-loaded, stimuli-responsive LbL coatings and for developing the next generation of biomedical coatings.