SYSTEMATIC STUDY OF HYDROGEN PEROXIDE GENERATION, BIOCOMPATIBILITY AND ANTIMICROBIAL PROPERTY OF MUSSEL ADHESIVE MOIETY

Author

Hao Meng, Michigan Technological UniversityFollow

Date of Award

2017

Document Type

Campus Access Dissertation

Degree Name

Doctor of Philosophy in Biomedical Engineering (PhD)

Administrative Home Department

Department of Biomedical Engineering

Advisor 1

Bruce P. Lee

Committee Member 1

Feng Zhao

Committee Member 2

Megan C. Frost

Committee Member 3

Lanrong Bi

Abstract

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.

Recommended Citation

Meng, Hao, "SYSTEMATIC STUDY OF HYDROGEN PEROXIDE GENERATION, BIOCOMPATIBILITY AND ANTIMICROBIAL PROPERTY OF MUSSEL ADHESIVE MOIETY", Campus Access Dissertation, Michigan Technological University, 2017.

https://doi.org/10.37099/mtu.dc.etdr/363