A Novel Polymeric Valve for Transcatheter Aortic Valve Replacement Minimally invasive transcatheter aortic valve replacement (TAVR) has emerged as an effective therapy for the unmet clinical need of inoperable patients with severe aortic stenosis (AS). Recent longitudinal follow-up studies of TAVR patients however indicate that this procedure and associated technology may result in serious adverse events. Current technology is based on tissue valves adapted to, but not specifically designed for TAVR. Those may sustain damage during crimping as well as deployment, are susceptible to bone-like calcific deposition, and suffer from limited durability. Our group has developed a novel valve that is specifically designed to tackle the numerous challenges that a TAVR valve will meet during its life cycle, from crimping to deployment and long term performance in situ. It incorporates (i) novel polymer technology, xSIBS, which combines superior bio-stability together with excellent mechanical properties, and (ii) a novel design optimization methodology of the leaflets profile for enhanced hemodynamic, durability, and thromboresistance performance. Our broad objective is to develop a viable and durable TAVR valve that will propose a real alternative to existing bioprosthetic aortic valves, and allow a long-term solution adequate for broader segment of the population. This Phase I STTR project, in a collaboration between Stony Brook University and PolyNova Cardiovascular Inc, aims to shift our existing novel polymeric prosthetic heart valve to a TAVR application, providing proof-of-concept. This will be tested in four aims: Aim 1 analyses the hydrodynamic performance in silico both in standard as well as in patient- specific anatomy, quantify its thrombogenic potential, and compares it to a commercially available valve. Aim 2 tests the hydrodynamic performance in vitro, using standard and patient-specific anatomy, and evaluates damage to the polymer as a result of valve crimping. Aim 3 quantifies the thromboresistance profile of the valve via platelet activation under physiological flow conditions. Aim 4 evaluates the durability performance and calcification susceptibility under accelerated wear testing conditions. Successful accomplishment of the above aims will lead to a breakthrough in the treatment of aortic valve diseases, providing an affordable, long-term, minimally invasive solution, enhancing the life of a much broader patient population.
Public Health Relevance Statement: Narrative The objective of this project is to provide in vitro feasibility of an advanced, new generation, prosthetic aortic valve for transcatheter aortic valve replacement (TAVR) procedure. This valve utilizes novel polymer technology combined with novel design optimization methodology, specifically designed to tackle TAVR challenges, with improved blood compatibility, hemodynamics, durability, and thromboresistance performance. This novel technology will lead to a landscape shift, providing a viable long-term solution for treating severe aortic valve disease.
Project Terms: 3D Print; Adverse event; Anatomy; Animals; aortic valve; aortic valve disorder; aortic valve replacement; Aortic Valve Stenosis; Berlin; Biological Assay; Bioprosthesis device; Blood; Blood Platelets; Blood Vessels; bone; calcification; Calcified; Cardiovascular system; Chronic; Clinical; Clinical Research; Collaborations; commercialization; Complication; Computer Simulation; crosslink; Cyclic GMP; Cyclization; Deposition; design; Deterioration; Devices; Dissection; effective therapy; Evaluation; experimental study; Extravasation; follow-up; Follow-Up Studies; Generations; Geometry; Goals; Grant; Heart; Heart Valve Prosthesis; hemodynamics; high risk; improved; In Situ; In Vitro; in vivo; innovation; Left; left ventricular assist device; Licensing; Life; Life Cycle Stages; Liquid substance; Measures; mechanical properties; Methodology; migration; minimally invasive; Modeling; Molds; National Institute of Biomedical Imaging and Bioengineering; new technology; novel; older patient; Operative Surgical Procedures; Outcome; Pathway interactions; patient population; Patient risk; Patients; Performance; Phase; Physiological; Plant Roots; Platelet Activation; Polymers; Population; Predisposition; Preparation; pressure; Procedures; Process; programs; Prosthesis; Protocols documentation; prototype; Publishing; quantum; replicator; research and development; Risk; Risk Factors; Rupture; Savings; Serious Adverse Event; Silicones; simulation; Small Business Technology Transfer Research; Stents; Stress; stroke; Structure; success; Surgical Valves; System; Technology; Testing; Therapeutic Embolization; Thick; Thrombosis; Tissues; Translating; United States National Institutes of Health; Universities; valve replacement; verification and validation; X-Ray Computed Tomography
