Date of Award

12-2016

Document Type

Thesis

Degree Name

Master of Science (MS)

Legacy Department

Bioengineering

Committee Member

Dr. Agneta Simionescu, Committee Chair

Committee Member

Dr. Dan Simionescu

Committee Member

Dr. Jeremy Mercuri

Abstract

Essential hypertension, characterized by elevated blood pressure levels, is a primary risk factor for other cardiovascular diseases. There has been a drastic rise in the amount of people who have essential hypertension; trends predict that 1.56 billion people worldwide will be living with essential hypertension by 2025. Anti-hypertensive drugs lower elevated blood pressure levels, but do not eliminate the disease itself or reverse the structural damage to arteries. This study aims to elucidate hypertension-induced endothelial cell (EC) dysfunction using a blood vessel tissue engineering approach as a pathology model. In order to characterize EC dysfunction, the FlexCell® system was used to induce a dynamic 140 mmHg transmural pressure onto EC monocultures and endothelial cell–smooth muscle cell (EC-SMC) co-cultures over the course of four days; control samples were subjected to 120-mmHg. Cell-matrix adhesion and cell-cell interaction were evaluated by EC culture studies and vasoregulation was the main focus for the EC-SMC co-culture studies. Immunofluorescence and western blots were used to detect integrin β1, FAK, and VE-cadherin, as well as eNOS, endothelin, and angiotensin. Additionally, a novel bioreactor platform was developed to simulate and control hypertension values. Cell-seeded vascular scaffolds were mounted into a bioreactor system that induced a flow rate of 150 mL/min and a hypertensive pressure profile, which matched that of a femoral artery found in the human body. Preliminary results showed that cells were able to attach and that the arterial structure remained intact. However, dynamic rotational seeding should be implemented for future studies for better cell attachment on arteries. This system could be tailored towards studying other vascular diseases, or modified to produce clinically relevant tissue engineered blood vessels, resistant to high blood pressure.

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