Date of Award

12-2014

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Legacy Department

Bioengineering

Advisor

Dr. Delphine Dean

Committee Member

Dr. Bruce Gao

Committee Member

Dr. Dan Simionescu

Committee Member

Dr. Frank Alexis

Abstract

In blood vessel engineering, an optimal bioartifical scaffold can be characterized as a 3D tubular structure with high porosity for nutrient diffusion and enough mechanical strength to sustain in vivo dynamic environment. The luminal surface of the scaffold is supposed to have a continuous layer of endothelial cell that is ideally non-immunogenic and non-thrombogenic while the media layer of the construct is assigned for the ingrowth of vascular smooth muscle cell which can provide structural integrity and contractility. While reconstructing endothelial cell layer has been at the center of interest in most polymeric vascular replacements related research, growing VSMCs has had less attention due to the high risk of their excessive proliferation and unexpected phenotype shifts that can result in vessel restenosis. In addition, finding a reliable source of VSMC can be a formidable task. As such, we believe that if VSMCs can be modulated to remain quiescent and functional over time after they are obtained from an alternative source, they might eventually be considered to incorporate into artificial vascular substitute. To achieve this goal, first we investigated the potential of using stem cell to differentiate into functional VSMCs. Next, we designed a 3D culture construct to mimic blood vessel with distinct layers and analyzed the effect of combining different biochemical and biomechanical signals on modulating VSMCs behavior. Finally, we developed a biomechanical model that can incorporate the mechanical property of differentiated cell and distinct layers with geometrical information acquired from confocal images to predict cellular behavior under different conditions. The results of these studies provide insights from a basic science prospective about the potential of using stem cell to obtain functional VSMCs and the impact of environmental factors on VSMCs behavior. Researchers may use these results to optimize the culture condition of VSMCs in order to modulate its proliferation, phenotype and mechanical property. The model developed in this study might be used to predict cellular behavior under different culture environments without repetitive experiments.

Included in

Biomechanics Commons

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