Parametric Engineering of Atrioventricular Living Valve Transplants

Abstract

Diseases of the (mitral and tricuspid) atrioventricular valves (AVV), which regulate inflow from the atria to the ventricles, can result in severe obstruction to inflow (stenosis) or valvular leakage (regurgitation), requiring surgical intervention. In patients with small annulus diameters (< 19 mm), valve replacement is a clinical challenge limited by prosthesis size constraints, lack of growth potential, suboptimal durability, and elevated thrombosis and bleeding risk. While living valve transplantation (LVT) has re-opened the possibility of using allogeneic valve tissue capable of growth and remodeling, translating this to the AVV has been challenging given the anatomical complexity of the sub-valvular apparatus. Here, we propose a strategy using a replacement bi-leaflet cylindrical valve fabricated from donor AVV tissue and artificial chordae, with a geometry designed to mimic the native AVV and engineered to satisfy predefined clinical targets. Pulse duplicator experiments allowed characterization of valve dynamics in terms of clinically important attributes framed as dimensionless parameters. A multi-objective optimization allowed us to identify an optimal design which we implemented in porcine AVV replacements (n=6). Our results demonstrated favorable hemodynamics with minimal regurgitation and stenosis, suggesting a promising method for patient-optimized valve replacements.