PB1171 - Design, Manufacturing and Testing of a Green Non-Isocyanate Polyurethane Prosthetic Heart Valve

Background: Valvular heart diseases affect about 40 million people worldwide. Valve replacement is the main effective treatment, using mechanical or biological prostheses. Mechanical valves represent constant risk of thromboembolism, while bioprostheses are prone to early degeneration. Considering the pressing need for hemocompatible and durable biomaterials, synthetic polymers can represent good candidates. Polyurethanes (PUs) have been tested as preferred mechanically resistant polymers but only one PU-based valve has been implanted in patients so far, due to calcification and degradation challenges. Additionally, PU synthesis requires the production of toxic isocyanates, responsible for severe health and environmental issues.

Aims: Our team focuses on the development of isocyanate-free polyhydroxyurethanes (PHUs), which represent the “green” alternative to PU. Our main goal is to synthesize and test innovative PHUs, derived from polypropylene glycol (PPG) or polytetrahydrofuran (PTHF), aiming at improved properties for use in prosthetic valves when compared to medical grade PU.

Methods: PPG and PTHF-based PHU networks were obtained by thermal-crosslinking. The materials were evaluated regarding calcification and hemo/biocompatibility upon incubation with different blood components and fibroblasts. PHU valve design was modeled by computational fluid-structure interaction, and tri-leaflet valves were produced by injection molding. Manufactured valves were tested in the aortic position of a pulse duplicator.

Results: PPG-PHU and PTHF-PHU did not trigger calcification. They were non-hemolytic. Activation of the contact phase of coagulation was strongly diminished compared to PU. Platelet adhesion on the surface of PHUs was drastically reduced compared to PU. Altogether, data confirm low thrombogenicity and improved hemocompatibility of PHU. Human fibroblasts kept their normal growth and shape upon contact with PHUs. PHU aortic valves showed ISO-compliant hydrodynamic performances, experiencing low regurgitation, normal transaortic flow, and effective orifice areas above the threshold.

Conclusion(s): In conclusion, this work sets up the basis for future development of a sustainable, hemocompatible and hydrodynamic-competent prosthetic heart valves made of PHU.