Decellularized Porcine Myocardium as a Scaffold for Cardiac Tissue Engineering
CommitteeTo, S. D. Filip
Williams, Lakiesha N.
Elder, Steven H.
Myocardial infarction (MI) and heart failure are leading causes of mortality globally. Recently, cardiac tissue engineering has become an attractive option for MI treatment due to the following advantages: it might provide optimal tissue performance maintained by viable transplanted cells, and might also stimulate the formation of vasculature supplying oxygen and nutrients in the patched region. However, fabrication of a thick viable cardiac patch with 3D scaffolds that are thoroughly recellularized with desired cells remains a challenge. We hypothesize that the decellularized porcine myocardium scaffold can preserve natural extracellular matrix (ECM) structure, cardiomyocyte lacunae, mechanical properties, and vasculature templates that are able to facilitate stem cell reseeding, proliferation, cardiomyocyte differentiation, and angiogenesis. In this dissertation, we have (i) assessed the potential of the decellularized porcine myocardium as a scaffold for thick cardiac patch tissue engineering; (ii) thoroughly characterized the structural and biomechanical properties of the myocardial ECM; (iii) designed and built a novel bioreactor that could provide coordinated mechanical and electrical stimulations, and (iv) evaluated the efficiency of the multi-stimulations on the development of a cardiac tissue construct. An optimized decellularization protocol has been identified to obtain the acellular myocardial scaffold that preserves subtle ECM composition and ultrastructure. We recellularized the acellular scaffold with bone marrow mononuclear cells using a rotating bioreactor and observed successful recellularization with good cell viability, proliferation, and differentiation in a 2-week culture time. Furthermore, we have successfully built a novel bioreactor that is able to provide coordinated mechanical and electrical stimulations for facilitating stem cell differentiation and tissue construct development. We found that cardiomyocyte differentiation and tissue remodeling were more effectively and efficiently promoted with the coordinated simulations, evidenced by good cell viability, proliferation, differentiation, positive tissue remodeling, and a trend of angiogenesis in a short period of time (2 - 4 days). The clinical product that we envision will benefit from the natural architecture of myocardial ECM, which has the potential to promote stem cell differentiation, cardiac regeneration, and angiogenesis. The hopes are that our novel approach will ultimately impact thousands of patients who have suffered significant damage from a prior myocardial infarction.