Electronic Theses and Dissertations

Identifier

1110

Date

2014

Date of Award

4-24-2014

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Biomedical Engineering

Committee Chair

Warren O. Haggard

Committee Member

Joel D Bumgardner

Committee Member

Erno Lindner

Committee Member

Tomoko Fujiwara

Abstract

Musculoskeletal injuries are some of the most prevalent injuries in both civilian and military populations and their infections can be difficult to treat, often resulting in multiple surgeries and increased costs. In both previous and recent military operations, extremity injuries have been the most common battlefield injuries and many involve complex, open fractures. These extremity injuries are especially susceptible to multiple pathogenic, and sometimes drug resistant, bacteria and fungi. Fungal infections have recently become increasingly problematic in both military and civilian populations and have significantly higher amputation rates than those from bacterial infections. Many of these bacterial and fungal strains adhere to tissue and implanted orthopaedic hardware within wounds, forming biofilms. These problematic, often polymicrobial, infections threaten the health of the patient, but the risk also exists of spreading within hospitals to become prominent resistant infections. Local antimicrobial delivery releases high levels of antimicrobials directly to injured wound tissue, overcoming sub-bactericidal or sub-fungicidal antimicrobial levels present in the avascular wound zones. This research will determine the ability of modified chitosan sponges, buffered with sodium acetate or blended with polyethylene glycol (PEG), to act as short term adjunctive therapies to initial surgical treatment for delivering both antibiotics and/or antifungals for early abatement of infection. The objective of this work was to evaluate both types of modified sponges for in vitro and in vivo material characteristics and device functionality. In vitro analysis demonstrated both the buffered and PEG modified chitosan sponges exhibited increased degradation and functional cytocompatibility. The chitosan/PEG sponges were able to be loaded with hydrophobic antifungals and the sponges released in vitro biologically active concentrations, alone or in combination with the antibiotic vancomycin. Both types of modified sponges exhibited good biocompatibility and slight, but not complete, degradation in an in vivo rat intramuscular degradation and biocompatibility model. In an in vivo bacteria biofilm infection prevention mouse model, vancomycin loaded chitosan/PEG sponges also cleared more bacteria than the unmodified chitosan sponges. These experimental results led to the conclusion that with additional research and in vivo studies, the buffered and PEG blended chitosan sponge local delivery systems exhibit potential for use as adjunctive bacterial or fungal infection prevention therapies to standard surgical treatment of musculoskeletal wounds.

Comments

Data is provided by the student.

Library Comment

dissertation or thesis originally submitted to the local University of Memphis Electronic Theses & dissertation (ETD) Repository.

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