Date of Award

December 2019

Document Type


Degree Name

Doctor of Philosophy (PhD)



Committee Member

Jeremy L Gilbert

Committee Member

Melinda K Harman

Committee Member

Martine LaBerge

Committee Member

Jeremy J Mercuri


There are many molecules, species and mechanisms that contribute to the overall wear and degradation of biometallic alloys like cobalt-chromium-molybdenum (CoCrMo). Following implantation, orthopaedic alloys are subject to an encompassing inflammatory response that will either lead to foreign body giant cell formation and attachment to the surface or the fibrous tissue encapsulation, forming an inflamed periprosthetic joint. In addition to the inflammatory response, tribocorrosion-based processes of alloy-on-alloy or alloy-on-polymer couples release polymeric wear debris, oxides, hydroxides, and metal ions in response to excessive wear, loading and corrosion. It is hypothesized that these processes, biological and triboelectrochemical, are linked together in a feedback-loop, and there is reason to believe that there exists a common catalyst, reactive oxygen species (ROS), that accelerates the cycle. This dissertation explains how ROS are generated in physiological conditions and how they affect electrochemical properties, under what circumstances ROS are consumed intracellularly, how different cell types respond to ROS-rich conditions, and how ROS interact with solution components native to synovial fluid, with a decisive effort and focus on defining their presence and role in the inflamed joint space.

By fluorescently labeling individual ROS like hydroxyl radicals (OH·) and hydrogen peroxide (H2O2), we were able to correlate ROS concentrations against time of applied voltage (-1V vs. Ref) as well as against applied voltage for 2 hours. It was found that there exist thresholds for both the production and consumption of ROS, and there is a voltage range for which ROS are produced in measurable quantities. Under similar electrochemical conditions, different cell types (pre-osteoblast-like MC3T3-E1, monocyte macrophage-like U937) were cultured and exposed to an influx of ROS through cathodic excursions. It was found that cells possess a unique ‘electrochemical zone of viability’ per phenotype with reduced glutathione (GSH) activity, a ROS scavenger molecule produced within inflammatory cells, hypothesized to be the oxidative stress suppressor in the U937 cells. This hypothesis was later confirmed when exposing macrophages (RAW 264.7) to simulated synovial fluid, where it was found that ROS (H2O2) had a significant (p < 0.05) effect on intracellular GSH activity (fluorescent intensity). In addition to influencing cell behavior and response, ROS production and exposure was found to alter electrochemical properties of CoCrMo surfaces. Using nearfield electrochemical impedance spectroscopy (NEIS), CoCrMo retrievals and CoCrMo surfaces damaged by electrocautery and ROS-rich solutions were shown to have significantly (p < 0.05) decreased corrosion resistance (RP) with increased constant phase element capacitance (CPE Q) and open circuit potentials (OCPs), indicating that ROS are major contributors in corrosion susceptibility.

By interpreting these observations and results, we were able to demonstrate that ROS are influential in several aspects of the inflammatory reaction to metallic biomaterials. The development of new diagnostics and predictive models centered around ROS can lead to safer practices involving orthopaedic alloys and further support our understanding of an inflamed joint space.



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