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Date of Award
Campus Access Dissertation
Doctor of Philosophy in Biomedical Engineering (PhD)
Administrative Home Department
Department of Biomedical Engineering
Bruce P. Lee
Committee Member 1
Committee Member 2
Committee Member 3
Committee Member 4
The biological responses of hydrogen peroxide (H2O2) are highly dependent on its concentration. H2O2 concentration between 102-103 µM is bacteriostatic and higher than 106 µM is antimicrobial. The introduction of relatively low concentrations of H2O2 (102-103 µM) promoted wound healing, while complete removal delayed wound healing to form incomplete eschar. In this work, we manipulated a unique reduction-oxidation (redox) chemistry found in mussel adhesive proteins (MAP) to create three biomimetic model systems for antipathogenic and wound healing applications. Catechol, an adhesive moiety found in MAP, autoxidizes to form semiquinone and quinone during which a considerable amount of H2O2 is generated as byproducts.
In the first study, a simple two-step, shaking-assisted polydopamine (PDA-contain catechol moieties) coating technique was used to impart surgical mesh with antimicrobial properties. In this modified method, a relatively large concentration of dopamine (20 mg mL-1) was first used to create a stable PDA primer layer, while the second step utilized a lower concentration of dopamine (2 mg mL-1) to promote the deposition of large aggregates of PDA nanoparticles. Gentle shaking was employed to increase the deposition of a thicker PDA coating with nano-scaled surface roughness. When PDA-coated mesh was hydrated in phosphate saline buffer (PBS, pH 7.4), it was activated to generate 200 µM H2O2 for over 48 h. The sustained release of low doses of H2O2 was antibacterial against both gram-positive, Staphylococcus epidermidis (S. epi, Log Reduction Value (LRV) ~ 1.97), and gram-negative, Escherichia coli (E. coli, LRV~3.15), bacteria.
In the second study, catechol-containing microgels were functionalized with hematin (HEM), a hydroxylated Fe3+ ion-containing porphyrin derivative to create a single microgel system that can generate highly reactive hydroxyl radical (•OH) when hydrated in an aqueous solution with physiological pH. In the presence of Fe2+ ions, H2O2 can decompose to form the •OH in a process known as the Fenton reaction. •OH is a potent oxidant with the ability to degrade hazardous organic compounds, kill bacteria, and inactivate viruses. The •OH-generating microgels were able to degrade organic dyes, exhibited antimicrobial activity against both E. coli and S. epi bacteria (initial concentration of 106-107 CFU/mL), and reduced the infectivity of a non-enveloped porcine parvovirus and an enveloped bovine viral diarrhea virus by 3.5 and 4.5 LRV, respectively.
Finally, a physically crosslinked gelatin microgel was functionalized with catechol moieties to study the effect of the persistent release of H2O2 on full thickness wound repair in genetically diabetic mice. Up to 86 µM of H2O2 was released from these microgels when hydrated in a neutral pH solution for over 24 h. H2O2-generating microgels exhibited antibacterial activity against S. epi bacteria (initial concentration of 103 CFU/mL), and accelerated dermal wound closure (up to 90%) and healing after 14 days post-surgery in genetically diabetic mice. A complete re-epithelialization, panniculus carnosus formation, and appearance of hair follicles were observed for the wounds treated with H2O2-generating microgels. Granulation tissue, deposited collagen, and keratinocytes seemed to recede to the fibroblast- and collagen-rich dermis layer, which is consistent with the morphology and structure found on native tissue. These results indicate a persistent release of low concentrations of H2O2 have the potential to accelerate the delayed wound healing.
Kord Fooroshani, Pegah, "MODEL POLYMER SYSTEMS CONTAINING CATECHOL MOIETIES TO TUNE HYDROGEN PEROXIDE GENERATION FOR ANTIPATHOGENIC AND WOUND HEALING APPLICATIONS", Campus Access Dissertation, Michigan Technological University, 2021.