Date of Award

2022

Document Type

Open Access Dissertation

Degree Name

Doctor of Philosophy in Biomedical Engineering (PhD)

Administrative Home Department

Department of Biomedical Engineering

Advisor 1

Rupak Rajachar

Advisor 2

Sean Kirkpatrick

Committee Member 1

Bruce Lee

Committee Member 2

Smitha Rao

Committee Member 3

Alexandre Zerbini

Committee Member 4

Jooke Robbins

Abstract

Satellite telemetry tags are used to track the migration patterns of large cetaceans. These tags penetrate the dermis and remain embedded in the underlying blubber tissue. As the dermis of cetaceans is host to a diverse microbiome, and it is impossible to clean the skin before implanting the devices, the potential for infection is increased when the tags penetrate through the skin. H2O2 is a potential antimicrobial agent that, in addition to showing broad-spectrum efficacy against gram-negative and gram-positive bacteria, can promote wound healing outcomes by promoting proliferative factors and peptides that protect against oxidative stress. However, delivering H2O2 in a controlled manner and maintaining a stable solution concentration has previously been difficult. Polydopamine (pDA) is one polymer that can release H2O2 in a controlled manner. During polymerization, the catechol on the monomer of dopamine will oxidize and generate H2O2. However, not all catechol will be oxidized after polymerization allowing for continued generation after coating deposition. This release profile can be tailored through simple changes in the coating environment such as solution pH, temperature, and coating time. We found, when exposed to a high pH (8.5) and an increased coating temperature (37℃) there was significantly more release compared to other coating conditions tested (40µM vs 80µM). These controlled doses of H2O2 generated through additional oxidization reduce bacterial adhesion from common terrestrial bacteria strains (Escherichia coli [70% reduction] and Staphylococcus epidermidis [25% reduction]) and aquatic strains from the two most populous genera located in the microbiome of healthy cetaceans (Psychrobacter [80% reduction] and Tenacibaculum [70% reduction]) on the surface of medical-grade stainless steel. H2O2 generated by our pDA coatings was also seen to be less toxic against model cell types over a 24 hour period indicating cells are more tolerant to H2O2 when delivered in a continuous dose as opposed to bolus doses. These same coatings, when introduced during the differentiation process, are able to promote the differentiation of pre-adipocytes into adipocytes (23% increase) and potentially induce dedifferentiation of adipocytes into their precursor cell types. In a model cell type, the pDA coatings also increase the endogenous expression of the antimicrobial peptide dermcidin (72% increase) without the same significant decrease in cell viability seen after a bolus dose of H2O2.

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