Abstract 15274: Pediatric Valved Conduit From Biological Engineering in the Growing Lamb Model

Abstract

Introduction: A valved conduit with growth potential for pediatric patients remains an unmet need. Here we present a novel valved conduit with growth potential based on initial data in a growing lamb model. The valve is constructed from three biologically-engineered tubes of acellular collagenous matrix possessing somatic growth potential (Syedain et al., Nat Comms, 2016) using resorbable suture with each tube contributing to create a “leaflet” (Syedain et al, Sci Transl Med, 2021). This tri-tube valve previously demonstrated growth over 52 weeks when implanted interpositionally in the pulmonary artery. Methods: In this study, a fourth tube of the same matrix is placed around the tri-tube valve to create a tubular valved conduit. The inlet segment is cut diagonally to allow for direct attachment to the myocardium, emulating a clinical repair (see figure). Results: The first two lambs to date implanted in this study exhibited normal leaflet function, a pressure gradient less than 5mmHg without regurgitation or dilatation of the conduit at 12-week echocardiography (see figure). During this time the animal’s weight increased from 34±2kg to 48±1kg. The inflow pattern with this myocardial implantation was more uniform than in the previous study that used a pulmonary artery interposition implant of the just the valve (with no conduit). Discussion: Demonstrating integration of the conduit’s matrix to the myocardium is a key step toward a clinical trial. Previous pulmonary interposition implants of the valve, while achieving integration with the adjacent artery prior to dissolution of the Maxon suture (50% loss of tensile strength in ~3 weeks, complete by ~26 weeks), did not establish this clinically relevant point of myocardial integration. Conclusion: The preliminary finding is that the valved conduit exhibits excellent function at 12 weeks in the growing lamb and integration of the conduit’s matrix with the valve annulus-myocardium will likely occur. Funding: R01 HL107572