Development and evaluation of the efficacy of regenerative human heart valve by decellularization of sheep heart valve

Among cardiovascular diseases, which cause almost 1 in 3 deaths worldwide, heart valve diseases are one of the most common types. There are two classes of valves developed for use in heart valve replacement operations: mechanical and bioprosthetic. However, mechanical valves have the disadvantages of requiring lifelong anticoagulation medication and are not suitable for paediatric patients. Bioprosthetic valves also have several disadvantages due to their short life span and immunological problems. All valve prostheses produced to date have a limited lifespan and require reoperation. Therefore, heart valve tissue engineering shows promise in overcoming the challenges of producing a viable, regenerative, biocompatible valve. In this direction, in order to create a starting matrix, heart valves obtained from different species were decellularised by various methods and their biocompatibility was tested. Although the valves tested were mostly derived from pigs, clinical results in the literature suggest that porcine valves fail in humans. Therefore, there is a need to evaluate acellular valves obtained from different species as a starting matrix. In addition, clinical trials of sheep heart valves have not yet been performed. Therefore, in order to shed light on clinical studies, in this thesis, for the first time, after decellularizing sheep pulmonary valves, an attempt was made to recellularize the acellular scaffold through the coculture of human umbilical cord endothelial cells (HUVEC) and human dermal fibroblast cells, and the potential of human cells to regenerate extracellular matrix (ECM) elements in the sheep valve matrix was investigated. According to the findings obtained, a high level of cell infiltration and a high level of recellularisation of the pulmonary artery wall was achieved and a significant increase in the gene expression of basic ECM proteins such as collagen and elastin was observed. Therefore, decellularised sheep heart valves have a high potential to provide an alternative to porcine counterparts or other prostheses as they are viable and regenerative after recellularisation with human cells.