Cardiac Tissue Engineering

Abstract

(Same as attached file) Introduction: Every year in the United States thousands of people lose their lives because of organ failure; in fact the leading cause of death is heart disease. There are several major issues for patients of organ transplantation. The two largest of these are the scarcity of suitable organs and the recipient’s immune system rejecting the organ. Tissue engineered organs are a very promising treatment because of their non-immunogenicity characteristics for patients who need an organ transplant. Blood coagulation in bioartificial organs is also a frequent problem which can be fatal after transplantation. The heart group in the Cook Tissue Engineering Lab in the BYU Chemical Engineering department is focusing on creating a transplantable bioartificial organ. In this study an economic, effective, and rapid decellularization process with minimum damage to a cardiac extracellular matrix (cECM) is described. In addition, a static blood assay for thrombosis control is developed and tested to verify the effect of decellularization on the thrombogenicity potential of the whole heart. Materials and Methods: Porcine hearts were freshly harvested from swines at a local abattoir. Researchers trimmed the cardiac vessels and removed excess fat. Tubes were connected to the aorta and pulmonary artery enabling retrograde flow in a bioreactor. The hearts were then perfused with cycles of 1X phosphate buffered saline (PBS), type I distilled water and 0.5% sodium lauryl sulfate solution for 24 hours. The total SDS exposure time was kept as low as 5 hours to minimalize mechanical damage to the cECM. After decellularization hearts were dissected to take samples for histology and scanning electron microscopy in order to determine the changes and configuration of the cECM and verify cell removal. Other decellularized hearts were preserved in PBS for a static blood thrombosis assay (SBTA). Freshly harvested hearts were used as a control for SBTA. The quality and quantity of thrombosis formed in the decellularized hearts were examined. Results: Successful decellularization of porcine hearts was achieved without significant damage to the cECM. Large amounts of thrombosis were observed in decellularized hearts while the thrombosis in fresh organs was negligible. The blood that was in contact with decellularized hearts was much more activated compared to the control group. Furthermore, adhesion of platelets to the walls of ventricles and auricles of decellularized hearts was quite explicit which verifies the thrombogenicity of cECM. Further investigation will be focused toward recellularization of the heart in order to obtain a functional organ and minimize the thrombogenicity of the heart.