| This research aimed to develop and test the first patient-specific hybrid heart valve with self-regenerating capacity, and potential for lifelong durability.;Valvular heart disease is the third most common cause of heart problems in the United States. Replacement of dysfunctional valves markedly reduces the morbidity and mortality associated with valve disease. Currently, only two main types of prosthetic heart valves (i.e., mechanical and bioprosthetic) are available to replace a diseased valve; each has major advantages and limitations, and surgeons try to match the valve choice based on the patient's particular clinical condition. Despite meaningful and encouraging early results for tissue-engineered heart valves, these valves are found to be mostly unable to adjust their composition to withstand various types of dynamic loads to which they are exposed in the heart, principally in the left ventricle.;To overcome these limitations, we approached the problem differently, by creating a hybrid heart valve based on a non-degradable scaffold that remains permanently and supports the leaflets, in contrast to currently used degradable scaffolds. The hybrid valve's leaflets are composed of an extra-thin superelastic Nitinol mesh, which is tightly enclosed by multiple layers of cells of the patient who will receive the valve. Due to this arrangement, this hybrid tissue-engineered valve will possess a smooth biological surface while its thin superelastic Nitinol core supports extracellular matrix backbone of the leaflet to withstand the variety of loads applied to it in the heart. This approach to engineering heart valves holds promise for combining the mechanical valves' long-term durability advantages with biological valves' improved biocompatibility and hemodynamics.;The long-term goal of this study is to shift the mainstream of heart valve research and development toward patient-specific living valves technology. Additionally, such a hybrid approach may find application in other areas of tissue engineering, such as vascular and bone tissue engineering. This is beyond the scope of this thesis. |
