Date of Award
Master of Science (MS)
Dan T. Simionescu
Cardiovascular disease (CVD) is a non-communicable disease responsible for 659,000 deaths annually in the United States. While CVD can affect all components of the cardiovascular system, heart valve disease is responsible for 25,000 deaths yearly. Of specific interest is the pulmonary valve since there is limited research on resolving pathologies that affect it. Like the aortic and mitral valves, common pathologies include stenosis, regurgitation, and atresia. Notably, the pulmonary valve requires repair and replacement in pediatric patients and young adults due to congenital disabilities. Even with technological advances in valve replacements, limitations still present themselves for use with younger patients as mechanical valves require lifetime anticoagulation medication, and bioprosthetic valves are prone to rapid degeneration and calcification. Both options have a relatively short lifespan and require multiple revision surgeries in young patients associated with high morbidity and mortality (Schoen, 2018). There is a significant clinical need for a pulmonary valve with extended durability to last the patient’s lifetime while limiting the risk of immunological response, degeneration, and calcification. We hypothesized that the most durable valve tissue would be cell-seeded living tissue capable of continuous matrix homeostasis throughout the lifetime of the implant.
In this project, we proposed a novel solution for a living pulmonary valve for young adult patients through the addition of patient-derived fibroblasts seeded into decellularized tissue scaffolds before the valve assembly. We had three specific aims for this research. 1) Determine the physical and mechanical properties of native pulmonary leaflets as target tissues and investigate potential decellularized scaffold tissues to serve as a building material for the valve 2) Compare two seeding methods for the chosen tissues, i.e., single needle manual injection and the CytoSeeder™, a novel cell seeding device developed in our lab, 3) Develop a proof-of-concept template and protocol for the manufacturing of the living pulmonary valve using a titanium valve stent, test hemodynamics of the assembled valve and evaluate cell viability of a fibroblast-seeded valve scaffold in a sterile heart valve bioreactor.
We found the most favorable decellularized tissue scaffolds to be bovine pericardium and bovine inferior vena cava based on mechanical properties, elasticity, thickness, and available surface area. During seeding studies, significant cell repopulation was observed by both seeding methods in the two scaffolds. Finally, bioreactor studies showed adequate opening and closing of the assembled valve under physiological conditions and preservation of cell viability. These results open promising new avenues for the development of living tissue valves with extended durability for young adult patients.
Hoskins, Erica, "Tissue-Engineered Living Pulmonary Valve for Young Adult Patients" (2022). All Theses. 3825.