R44HL129577

Project Summary: Congenital heart disease (CHD) remains the most common category of birth defect and a leading cause of childhood death in the developed world. Of the constellation of structural defects that comprise CHD, dysfunctional pulmonary valves (PV) are a common abnormality, and frequently require surgical intervention and replacement. Valve replacement through open heart surgery carries substantial risk and discomfort for patients, and represents a major financial and emotional burden for families. The most commonly used valves for pulmonary valve replacement in young children are biologically-derived (e.g. human cadaveric valves). Such replacements are in short supply, and have other inherent disadvantages, such as poor long-term durability, and propensity to induce a host immune response. The combination of these factors leads to a cycle of repeat surgical interventions, using valves that are scarcely available and destined for rapid failure. PolyVascular has sought to address these issues by developing a polymeric stent-mounted valve (SMV), comprised of polymer-derived leaflets mounted within a metal stent, that can be delivered via minimally invasive transcatheter techniques, avoiding the burden of repeat surgeries, with potential for improved durability and function. The present supplement is meant to support Kelly McKinzey’s training in medical device development with PolyVascular in preparation for an independent career leading health-related research and development for small businesses, under PA-18-837. The proposal consists of two training components: in the Research Plan, Ms. McKinzey will employ alternate methods for leaflet fabrication, and test these against PolyVascular’s standard methods. She will gain training in stent mounted valve manufacturing, polymer chemistry, ISO 5840-3 benchtop testing, ISO 10993 biocompatibility testing, sterilization validation, and packaging validation. All steps will be conducted under a quality system, and Ms. McKinzey will gain experience in adhering to this system. A second training component involves her Career and Mentorship Plan, in which she will take advantage of the startup ecosystem in the Texas Medical Center, through courses at Enventure and other local institutions. She will gain experience in entrepreneurship and responsible conduct of research, within the framework of device development for FDA approval. Both elements of the proposal are intended to surround Ms. McKinzey with an interdisciplinary team of experienced researchers, and ready her for a career in medical device development.Project Summary: Patients born with congenital heart defects often require replacement of their pulmonary valve, which allows the heart to pump to the lungs. Conventionally, such valve replacements require open-heart surgery, which carries significant risk and discomfort. Our proposal describes the development of a new heart valve platform, across a range of sizes for small children, adolescents, and adults, which can be delivered in a minimally-invasive fashion through the groin without open-heart surgery.