Date of Award
12-2022
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Bioengineering
Committee Chair/Advisor
Agneta Simionescu, PhD
Committee Member
Dan Simionescu, PhD
Committee Member
Jeremy Mercuri, PhD
Committee Member
Christopher Wright, MD
Abstract
Cardiovascular Disease(CVD) is the leading cause of mortality in the developed world. CVD is most commonly manifested as atherosclerosis of the coronary arteries leading to Myocardial Infarction(MI). After MI, fibrosis of the ventricular wall leads to heart failure(HF), a pandemic affecting 26 million people globally. While therapies are continuously developed to combat HF, the treatment of choice, whole heart transplant, is limited by the availability of donor hearts. It is clear that there is a need to develop a long-term solution to combat HF and its enormous economic burden. Tissue Engineering and Regenerative Medicine holds promise as a possible solution through the development of cardiac grafts capable of returning the function lost from MI. Current efforts in the development of cardiac tissues have been plagued by the inability to generate tissues of sufficient thickness(>100μm) or contractility of mature tissue, resulting in low engraftment rates or lacking efficacy. This leads to the focus of this research being the generation of a thick vascularized cardiac patch capable of long-term survival. First, we decelled whole porcine hearts for the production of ventricular flap and myocardial scaffolds. Scaffolds showed no evidence of retained cellular content or DNA, but retained key characteristics of the extracellular matrix and maintained the same mechanical properties as native tissue. We then performed a combined cell seeding to reendothelialize the vasculature of the ventricle wall and repopulate the myocardium. Finally, we developed a custom perfusion electromechanical bioreactor for the purpose of conditioning and maintaining the viability of our patch long term. We expect that this research will result in the development of cardiac grafts with long-term implications for therapy to solve MI related HF.
Recommended Citation
Herbert, Howard, "Development of a Tissue Engineered Cardiac Patch" (2022). All Dissertations. 3241.
https://open.clemson.edu/all_dissertations/3241