Development of a Polymeric Percutaneous Pulmonary Valve for Use in Young Children

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. In the present SBIR Phase II application, we seek to expand this model by developing a broader series of sizes, based on our existing platform design. This builds on data from our previous STTR Phase I proposal, which demonstrated the feasibility of an “extra-small” (XS) sized SMV, suitable for use in very small children with failing right ventricular outflow tract (RVOT) conduits. By expanding this series to S, M, L, and XL, in the present proposal, we can address even broader pediatric needs, such as eventual patient growth beyond the usable range of an “XS” SMV, and concentric stent-in-stent deployment. Larger SMV sizes also have clear use for other pediatric patients, such as teenagers with prior patch augmentation of the RVOT; this indication requires a far larger diameters than the “XS” target range. This proposal will focus on the necessary design and characterization steps to demonstrate the utility of the full family of SMV sizes, and provide data to FDA for evaluation. Aim 1: Design expanded size SMV stents, and assess just the metal stents for performance via ISO 25539 testing. Aim 2: Manufacture complete SMVs in the expanded SMV sizes, and conduct necessary tests via ISO 5840-3 to document SMV performance and durability. Aim 3: Biocompatibility testing and transfer a suitably-sized SMV to a GLP sheep model for acute and extended evaluation of valve performance, calcification, thrombosis, and local tissue response. These studies are intended to generate data that clarify overall SMV platform performance, and potential use cases, and support first in human trials.