Year: 2021
Type: dissertation
Abstract: Increased bone fragility can stem from age-related and chronic bone affecting diseases (such as \nosteoporosis, diabetes and kidney disease), chemotherapeutic and radiation-based cancer treatments, \nand/or trauma and results in massive annual cost to the healthcare system and decreased quality of life \nfor patients. In order to ameliorate these problems, an in-depth understanding of the cause of \nincreased bone fragility is necessary. Oxidative stress, also known as inflammation, is hypothesized \nto be a key mechanism of causing oxidative damage in cortical bone’s collagen phase, thereby \nincreasing its fragility; however, this mechanism has not yet been confirmed. Operating under this \nhypothesis, the present work sought to 1) design an in vitro model of controlled and elevated \nphysiologically-relevant oxidative damage using bovine cortical bone, 2) conduct pore network \nmodelling of the transient reactive diffusion occurring within the bovine cortical bone’s porous \nstructure to inform operation of the in vitro model, and 3) validate the pore network model \nexperimentally using results from the in vitro model. \nA first-of-its-kind technique was developed to create controlled levels of oxidative damage in bovine \ncortical bone beams in vitro using free radicals generated from the decomposition of hydrogen \nperoxide using a Co2+ catalyst in aqueous solution. Pore network modelling (PNM) of this \nsystem indicated that the decomposition reaction proceeded extremely fast, which caused the greatest \nconcentrations of hydrogen peroxide to exist at the specimens’ surfaces and limited diffusion of hydrogen peroxide into the \nbone’s porous network. This was also the first ever application of PNM to study reactive transient \ndiffusion in bone and was valuable for informing the operation of the in vitro model. A novel \nfluorescent tissue staining technique for carbonyls, differing from current assay-based approaches, \nwas developed to visualize the oxidative damage gradient within the bone beams, and images \ngenerated using this technique qualitatively validated the pore network model. No statistically \nsignificant differences or correlations were observed between different treatments or hydrogen peroxide \nconcentrations and work to fracture, fracture toughness, maximum deflection, and mean pixel \nintensity. Statistical significance was not assessed for pixel intensity distributions (n = 1). This work \nprovides important contributions to the study of oxidative stress and bone fragility in the form of a \nnovel application of PNM to bone and new techniques for both causing and characterizing oxidative \ndamage in tissues. These techniques may be applied to other biological materials and human tissues \nto address the paucity of much-needed foundational knowledge for the study of oxidative stress, \ndamage, and tissue fragility in biological systems.
Source: UWSpace (University of Waterloo)
Author: Cyrus Jean-Baptiste Molavi Fiori
Language: English
Subfield: Orthopedics and Sports Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3194472140