Vascular mechanobioengineering

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Cardiovascular diseases represent an important burden for society. Atherosclerotic plaques develop as early as childhood and systemic risk factors have been identified, along with potential preventative and therapeutic avenues. Given the current pandemic, efforts are targeted towards diagnosis, through biomarker identification and molecular imaging development, and treatment, by developing novel molecules. Atherosclerosis develops focally and is linked to endothelial mechanobiology. In vitro, ex vivo and in vivo studies identified hallmarks of atherosclerosis such as expression of inflammatory markers. Arterial remodelling alters vessel wall geometry, as well as extracellular matrix composition/orientation, through the action of matrix metalloproteinases and their inhibitors, and cellular content, through migration, proliferation and apoptosis, potentially affecting progression and outcome. Understanding the effects of remodelling on mechanobiology can provide novel targets for earlier detection and improved treatments. Regulation of inflammatory markers and matrix metalloproteinases will be examined in vitro. The main objectives are to (1) design and validate in vitro systems for mechanical stimulation, (2) study inflammatory response of endothelial cells exposed to wall shear stress or cyclic strain in uniform geometry scaffolds, and (3) characterize endothelial cell response under complex mechanical stimuli (both hemodynamic shear and mechanical strain) in scaffolds mimicking remodelled arteries. The developed in vitro models will provide tools to the research community for mechanobiological studies, allowing tests on other cell types, pharmaceutical agents and in other pathological contexts. The biomarkers identified will provide potential new drug therapies, of interest to the pharmaceutical industry, and targets for molecular imaging probes that are being developed. Mechanobiological studies will provide crucial information on biomarkers, eventually leading to increased life expectancy/quality and benefiting individuals which in turn will have both a positive social and economic effect on Canada.