PROJECT SUMMARY - PEDIATRIC HEART VALVE WITH EXPANSION CAPABILITY Congenital heart valve defects are detected in nearly 40,000 infants born in the United States each year (Alsoufi 2014). The heart valve defect can range in severity, with about 25% of cases (about 13,000) requiring immediate open- heart surgery to replace the valve or other heart defects. Currently, there is no surgical heart valve prosthesis that meets the size, flow, and developmental needs of infants (Alsoufi 2014). Options include mechanical, bioprosthetic, homograft, or autograft (Ross procedure) valves. However, the most commonly used, mechanical and bioprosthetic valves, are designed with adults in mind (Schoen 2018). Thus, surgeons must alter the structure of the valve in the operating room effectively altering the hemodynamic profile and minimizing the flow potential. In addition, mechanical and bioprosthetic valves are stagnant, meaning that children often face patient-prosthesis mismatch and multiple operations as a result of their somatic growth (David 2016). Outside of growth, mechanical valves require life-long anticoagulation medication and bioprosthetic valves tend to undergo structural valve degeneration (Schoen 2018). In response, our team hypothesized that a replacement heart valve that can increase in size with a growing child and that can repair and model itself to last the child’s lifetime will greatly improve the quality of life of this patient population. The research team is composed of Dr. Leslie Sierad with expertise in bioreactor development and manufacturing, Dr. Dan Simionescu with expertise in valve design, scaffolds and cell seeding, Dr. Minoo Kavarana with extensive expertise in surgical approaches to treatment of congenital heart defects, and Dr. David Orr with experience in business development and regulatory affairs. To this end, we are proposing to manufacture and test stent valve prototypes that can increase in size from 12mm to 24mm through up to 4 balloon angioplasty interventions, each step increasing the diameter by 3 mm. The design will incorporate acellular pericardium as the biological tissue leaflets or cusps, tested for proper hemodynamics (specific Aim 1). In the second stage, the tissues will be seeded with human fibroblasts and endothelial cells obtained by in vitro differentiation of human adipose-tissue derived stem cells. The living valve prototype will be tested through “mock” implantation and expansion in a heart valve bioreactor already developed and patented by Aptus Bioreactors (specific Aim 2). During and after bioreactor testing, we will validate valve leaflets motions and hemodynamics, tissue mechanical properties, cell viability and phenotype. These studies will provide substantial proof of concept in support of the device and generate data in support of a Phase II large animal study which will utilize autologous cells for seeding of the leaflets and implantation of the expandable valves in juvenile sheep for safety ...