Optimized development of novel leaflet biomaterials for replacement heart valves

Project Summary The ideal replacement heart valve (RHV) should have sufficient durability, resistance to thrombosis, and excellent hemodynamics that lasts the remaining patient lifetime, which does not yet exist. The majority of current RHV are ‘bioprosthetic’ heart valves (BHV), with leaflets fabricated from chemically treated pericardium, as originally developed in 1971. While providing for an initially effective therapy, all BHV continue to suffer from limited durability resultant from mineralization and mechanical fatigue. The growing use of minimally invasive transcutaneous designs that utilize thinner leaflets results in even greater leaflet mechanical demands and may suffer from more limited durability. In addition, all pericardial biomaterials have intrinsic structural variability that greatly limits their ability to be further improved for extended durability. This present lack of improved RHV biomaterials continues to limit our ability to adequately address RHV limited durability. We have developed a class of hydrogel-coated electrospun (HES) biomaterials for cardiovascular applications. HES biomaterials have been successfully utilized as vascular grafts, in which a luminal hydrogel provided thromboresistance and an electrospun mesh sleeve provided mechanical reinforcement. HES biomaterials can be fabricated over a wide range of mechanical behaviors that encompass RHV design requirements, which we have shown can be accurately modeled. When combined with our high speed RHV simulation methods, it is possible to identify optimal biomaterial and leaflet geometry characteristics, so that we can develop RHV with greater durability. To facilitate both HES biomaterial development and leaflet functional performance, we will extend a novel non- contacting optical method to sensitively detect fiber structures with pixel-level resolution and exploit our significant in vitro and large animal model evaluations. We thus hypothesize that the rational development of HES biomaterial-based RHVs will lead to a new generation of durable replacement heart valves.