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The gold standard treatment for patients with AVD is surgical replacement of the aortic valve with either mechanical or fixed tissue prostheses. These implants have a limited lifespan and are associated with serious adverse events. Patient autologous tissue engineered heart valves (TEHVs) offer a solution. Vital to the development of a TEHV is determining a source of donor tissue(s) that most closely mimics the native valve tissue. In pursuit of determining an alternative cell source for patient autologous TEHVs we compared a number of phenotypic and genotypic characteristics of atrial fibroblasts, dermal fibroblasts and differentiated bone marrow-derived progenitor cells (BMCs) and made a comparison to valvular interstitial cells (VICS). We demonstrate that while VICs share some phenotypic similarities with fibroblasts and BMCs, they also possess unique characteristics and demonstrate differential mRNA expression of key regulatory pathways that may influence their phenotype. / October 2016

Heart valve tissue engineering (HVTE) stands as a potential intervention that could reduce the prevalence of congenital heart valve disease in juvenile patients. Prior studies in our laboratory have utilized mechanobiological testing to quantify the forces involved in the development of heart valve tissue, utilizing a Flow-Stretch-Flexure (FSF) bioreactor to condition bone marrow stem cells (BMSCs)-derived valve tissue. Simulations have demonstrated that certain sets of flow conditions can introduce specific levels of oscillatory shear stress (OSS)-induced stimuli, augmenting the growth of engineered valves as well as influencing collagen formation, extracellular matrix (ECM) composition and gene expression. The computational findings discussed in this thesis outline the methods in which flow conditions, when physiologically relevant, induce specific oscillatory shear stresses which could not only lead to an optimized valve tissue phenotype (at 0.18≤ OSI≤ 0.23), but could identify native valve tissue remodeling indicative of aortic valve disease.