Theses and Dissertations

ORCID

https://orcid.org/0000-0001-9226-385X

Advisor

Priddy, Lauren B.

Committee Member

Elder, Steven H.

Committee Member

Jennings, Jessica Amber

Committee Member

Kundu, Santanu

Committee Member

Swanson, Elizabeth

Date of Degree

8-13-2024

Original embargo terms

Visible MSU Only 1 year

Document Type

Dissertation - Campus Access Only

Major

Biomedical Engineering

Degree Name

Doctor of Philosophy (Ph.D.)

College

James Worth Bagley College of Engineering

Department

Department of Agricultural and Biological Engineering

Abstract

Osteomyelitis or infection of bone is painful and difficult to treat due to limited tissue penetration by antibiotics. A resulting chronic infection has around a 30% chance of never resolving and resulting in amputation of the limb. The current standard of care for osteomyelitis is debridement and systemic antibiotics for two to six months, which can cause systemic toxicity and increase the emergence of antibiotic-resistant bacteria. It is therefore necessary to develop a localized biodegradable treatment that can deliver high concentrations of antimicrobials while minimizing the risk of systemic side effects. The overall objective of this work was to develop, characterize, and challenge locally delivered chitosan-based biomaterials loaded with either antibiotic or alternative antimicrobial agent(s) in either chronic or acute rat osteomyelitis models. The specific aims were to: (i) determine the chemical and biological interactions between chitosan hydrogels and fosfomycin in vitro, (ii) evaluate the antimicrobial efficacy of chitosan hydrogel loaded with fosfomycin antibiotic, either in the gel, in polylactic acid microparticles, or in both gel and microparticles in vitro and in a chronic rat osteomyelitis model, compared to blank chitosan hydrogel, and (iii) evaluate the antimicrobial efficacy of electrospun chitosan membranes loaded with cis-2-decenoic acid and/or bupivacaine in an acute rat osteomyelitis model, compared to current standard Celox™gauze. As hypothesized, chitosan biomaterials loaded with antimicrobial(s) reduced the bacterial burden and disease symptoms when compared to the standard treatment or blank materials. In closing, locally administrated antibiotics with prolonged availability via engineered biomaterials such as chitosan may allow for increased therapeutic efficacy against osteomyelitis.

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