Electronic Theses and Dissertations

Date

2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Biomedical Engineering

Committee Chair

Jessica Jennings

Committee Member

Joel Bumgardner

Committee Member

Warren Haggard

Committee Member

Tomoko Fujiwara

Abstract

Microbial contamination and biofilm formation in complex musculoskeletal trauma is an ongoing clinical challenge. Infection and biofilm formation in these injuries cause significant pain in addition to physical, socioeconomic, mental, and familial burdens to patients while increasing strains on the healthcare system. Biofilm based infections are prevalent and are particularly difficult to treat due to the biofilm's tolerance to antimicrobials and ability to evade natural body defenses. Primary strategies to treat biofilm are 1) inhibition, 2) dispersal, and 3) removal. A promising strategy is to use the biofilm dispersal agent 2 decenoic acid (2DA) and its analogs combined with antimicrobials to inhibit and treat biofilm based infections. Also, high concentrations of local anesthetics (LA) that effectively block pain locally may provide advantages for preventing and treating biofilm based infections. Local antimicrobial delivery systems offer benefits over systemic delivery of therapeutics, but release kinetics, residency time, and ability to deliver hydrophobic therapeutics, i.e., LA and 2DA, are challenging. Burst release of antimicrobials is ineffective at eradicating infection and may also contribute to the growing incidence of antimicrobial tolerance. Surface modifications of chitosan biomaterials through acylation have demonstrated an ability to improve hydrophobic therapeutics' release kinetics while supporting wound healing. In these studies, we investigated the combinatorial antimicrobial effects of 2DA and LA for common pathogenic microorganisms. We further tested the hypothesis that direct acylation of chitosan with 2DA analogs could inhibit biofilm formation. We then evaluated the efficacy of acylated chitosan biomaterials in releasing therapeutics and treating biofilm based infections in in vitro and in vivo infection models.Results revealed that combinations of LA 5 mg mL 1 and 2DA 250 mg mL 1 have additive or synergistic activity against microorganisms. We confirmed that chitosan biomaterials could:1.Be directly acylated with 2DA to resist biofilm formation even without therapeutics loaded.2.Extend the release of loaded therapeutics to at least one week after acylation.3.Reduce infection occurrence in both in vitro and in vivo infection models after acylation and loading with 2DA and LA.

Comments

Data is provided by the student.

Library Comment

Dissertation or thesis originally submitted to ProQuest

Download

Share

COinS