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SYSTEMATIC STUDY OF HYDROGEN PEROXIDE GENERATION, BIOCOMPATIBILITY AND ANTIMICROBIAL PROPERTY OF MUSSEL ADHESIVE MOIETY
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
Megan C. Frost
Committee Member 3
Mussel adhesive moiety, catechol, has been utilized to design a wide variety of biomaterials. Oxidation of catechol to form highly reactive quinone is a necessary step to further involve into different reaction pathway to form intermolecular crosslinking (hardening adhesive and adhere to tissue). However the biological responses of mussel inspired biomaterials associated with the by-products generated during oxidation of catechol has never been characterized. In previous studies, cytotoxic level of hydrogen peroxide (H2O2) was captured in the dopamine doped cell culture medium. However, correlated in vivo studies did not investigated in these studies due to the lack of desirable model systems work as dopamine carriers. Additionally, the biological responses to the H2O2 are highly dependent on H2O2 concentration. Lower concentration of H2O2 promoted wound healing whilst higher concentration of H2O2 killed bacteria. Therefore, model hydrogel system was modulated into different physical appearance (bulk, injectable and microgel) to determine H2O2 production pattern and its biological responses and antibacterial property. The model system 1 was using catechol modified non-degradable bulk hydrogel (polyacrylamide, PAAm) to study H2O2 production during autoxidation of the catechol. 102 −103 μM concentration of H2O2 generated from hydrogel bound catechol and resulted in in vitro cytotoxicity and elevated in vivo foreign body reaction. The model system 2 was using 4-armed polyethylene glycol polymer end-capped with dopamine (PEG-D4) to characterize the production of H2O2 during the oxidant-mediated oxidative crosslinking of catechol. The maximum of 40 μM H2O2 generated from catechol moieties at the first 6 hours but ceased to generate H2O2 after the crosslink finished. Lower concentration of H2O2 exhibited localized cell responses in the culture (cytotoxicity) and in vivo (M2 macrophages differentiation). To maximum H2O2 production and diffusion, we developed a catechol modified recyclable microgel system (hydroxyethyl acrylamide, HEAA) which can be stored as dried powder and initiated H2O2 production only after mixing with liquid solutions (system 3). 103−5x103 μM of H2O2 was captured in microgels extract for 4 days and function as an effective bactericide agent. This dissertation addressed the H2O2 concentration from several micromolar to millimolar can be actively monitored to fit various types of applications.
Meng, Hao, "SYSTEMATIC STUDY OF HYDROGEN PEROXIDE GENERATION, BIOCOMPATIBILITY AND ANTIMICROBIAL PROPERTY OF MUSSEL ADHESIVE MOIETY", Campus Access Dissertation, Michigan Technological University, 2017.