Bacteria-Responsive Biomaterials for Prevention, Detection, and Treatment of Infections

Alkekhia, Dahlia

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Year:: 2020
Contributor:: Alkekhia, Dahlia (creator); Shukla, Anita (Advisor); Mathiowitz, Edith (Reader); Fuchs, Beth (Reader); Sello, Jason (Reader); Tripathi, Anubhav (Reader); Brown University. School of Engineering (sponsor)
Genre:: theses
Subject:: Polymeric drug delivery systems; antibacterial biomaterials; bacteria-responsive; polymeric multilayer films; hydrogels; diagnostics
Extent:: xx, 225 p.

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Abstract:: Bacterial infections can be difficult to treat and potentially lethal due to the rising global threat of antibiotic resistance. Systemic administration and overuse of antibiotics exacerbate antibiotic resistance. There is a need for therapeutic approaches to protect against infections, detect the presence of antibiotic resistant bacteria, and provide highly controlled delivery of antibacterial agents, to reduce development of antibiotic resistance. This thesis focused on developing 1) coatings to prevent and treat device-associated bacterial infections, 2) biomaterials with facile colorimetric indication of antibiotic resistant bacteria, and 3) bacteria-responsive biomaterials as a platform for spatiotemporally controlled delivery of antibacterial agents to limit unnecessary exposure to drugs. Natural and synthetic polymers, including newly developed responsive polymers, were utilized to formulate these biomaterials. Layer-by-layer self-assembly was used to form multilayer polymeric films with hyaluronic acid and poly-L-lysine (PLL), an antibacterial polypeptide. These coatings reduced bacterial attachment to surfaces (critical for biofilm prevention) and inhibited planktonic cell growth. PLL mobility, governed by molecular weight, influenced coating stability, antibacterial mechanism of action, and extended efficacy over repeated exposure to bacteria. Additionally, in this thesis, β-lactamases (βLs), the most prevalent cause of antibiotic resistance, were used as enzymatic triggers for bacteria-responsive biomaterials. To develop biomaterials with a facile, colorimetric indication of bacterial infection, a chromogenic βL substrate was synthesized and covalently tethered to polymers. The polymer conjugates and hydrogels formulated using these conjugates changed color from clear to yellow specifically in the presence of βLs and βL-producing bacteria. A βL cleavable compound was also synthesized and used to crosslink poly(ethylene glycol) hydrogels encapsulating a model drug carrier (polystyrene nanoparticles). βL-producing bacteria specifically degraded these hydrogels triggering cargo release. Our studies demonstrated how hydrogel properties (polymer density) and environmental factors (βL concentration and specificity, bacterial growth conditions) influence rates of hydrogel degradation and cargo release. The biomaterials developed here have the potential to prevent, detect, and treat bacterial infections.
Notes:: Thesis (Ph. D.)--Brown University, 2020

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Rights: In Copyright
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Alkekhia, Dahlia, "Bacteria-Responsive Biomaterials for Prevention, Detection, and Treatment of Infections" (2020). Engineering Theses and Dissertations. Brown Digital Repository. Brown University Library. https://repository.library.brown.edu/studio/item/bdr:1129431/

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Engineering Theses and Dissertations

Theses and Dissertations for the Engineering department.
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