Electronic Theses and Dissertations

Date

2025

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Biomedical Engineering

Committee Chair

Jessica Jennings

Committee Member

Hongsik Cho

Committee Member

Joel Bumgardner

Committee Member

Tomoko Fujiwara

Abstract

Drug tethering techniques play a crucial role in release kinetics, stability, and bioavailability of drugs, allowing them to meet specific medical needs. In this work, we have evaluated two tethering techniques of therapeutics with chitosan nanofibers, a widely used local drug delivery depot for its biocompatibility, non-toxicity, biodegradability, and high surface area-to-volume ratio. In one of the approaches, drugs were tethered through non-covalent hydrophobic interaction with acylated chitosan nanofiber, and release of hydrophobic antibiofilm fatty acids was studied, and their antimicrobial activity was evaluated against S. aureus bacteria. Weak hydrophobic interaction can hold the release for a short period, where the acyl chain length and membrane thickness can influence the release rate. In the second approach, the drugs were covalently conjugated with chitosan nanofibers with an ester bond, which can break in response to low or high pH and bacterial lipase, allowing stimuli-responsive release of attached omega-3 fatty acids, which was significantly antimicrobial against two common wound pathogens- methicillin-resistant S. aureus and P. aeruginosa. Omega-3 conjugated membranes were cytocompatible, although they did not induce fibroblast migration. These tethering techniques can be used to load therapeutic fatty acids for specific clinical needs such as short term (non-covalent) release in cases of prevention of infection immediately after surgery or long term (covalent) prevention of implant associated infections.

Comments

Data is provided by the student.

Library Comment

Dissertation or thesis originally submitted to ProQuest.

Notes

Embargoed until 08-08-2027

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Available for download on Sunday, August 08, 2027

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