Rotello, VincentChen, MinFarkas, MichelleMorita, YasuNabawy, Ahmed2024-12-112024-12-112024-0910.7275/55189https://hdl.handle.net/20.500.14394/55189Biofilm-associated infections present a clinical challenge, with biofilms protecting resident bacteria from host immune response and therapeutic agents. Severe biofilm infections annually afflict 300 million people worldwide, with treatment costing $25B in the US alone.Clinical treatment of refractory chronic wound infections combines surgical removal of infected tissues with long-term antibiotic therapy. Debridement is an invasive process and use of antibiotics selects for drug resistance, further increasing therapeutic challenges with chronic wound infections. Polymeric nanomaterials provide a promising opportunity to effectively address bacterial and biofilm infections.Polymers can be engineered to combat biofilm infections by tuning their morphological and physicochemical properties, including size, shape, and surface chemistry. In this dissertation, I demonstrate polymer-based strategies for the treatment of biofilm-associated infections, with a focus on wound biofilms. In the initial studies, we leveraged poly(oxanorborneneimide)-based biodegradable polymeric nanoemulsion to deliver plant-derived essential oil, including carvacrol, that can penetrate and eliminate bacterial biofilms. Next, we build upon this nanoemulsion platform and encapsulate two hydrophobic antimicrobial agents (eugenol and triclosan) into this nanoemulsion for synergistic treatment of wound biofilms. Notably, this combination nanoemulsion mitigates resistance development of antimicrobial triclosan and clears 99% of bacterial load in severe wound biofilm infections in mice. In a related system, I developed an antimicrobial nanoemulsion composed of all nature-derived materials. This nanoemulsion uses gelatin as a scaffold and carvacrol (from oregano oil) as the active antimicrobial phytochemical. Crosslinking of the gelatin scaffold using riboflavin (vitamin B2) led to a formation of a stable nanoemulsion with excellent antifungal activities against <em>C. albicans</em> biofilms. In a following study, I have leveraged this all-natural gelatin nanoemulsion to encapsulate transition metal catalysts (TMCs) for bioorthogonal catalysis in biofilms. This emulsion nanocatalyst can efficiently penetrate biofilms and eradicate mature bacterial biofilms through bioorthogonal activation of a pro-antibiotic, providing a highly biocompatible platform for antimicrobial therapeutics. The last parts of this dissertation focus on developing polymers with inherently antimicrobial activity for topical applications in wound biofilms. Our strategies include 1) integration of antimicrobial poly(oxanorborneneimide)-based polymer into hydrogel materials, 2) development of cationic conjugated polymers for simultaneous biofilm imaging and therapy. In summary, Polymer nanotherapeutics offer a promising alternative to antibiotics, alleviating challenges faced in the post-antibiotic era.Dissertation (Open Access)https://orcid.org/0000-0001-6505-4606