An Ascorbic-Acid Containing Poly(Carbonate) Urethane With Antioxidant Bioactivity for Application in Heart Valve...

Prosthetic heart valve development consists of several branching, innovative strategies to mediate the complex native environment that wears down valve durability. Anti-calcification treatments are being applied to pericardial tissue, durable polymers are being developed that mitigate oxidative degradation and stress cracking, and heart valve tissue engineering has introduced resorbable scaffolds that can develop into stable, functional tissue. In each case, an increasing breadth of strategies is being developed to curb the persistent issue of valve deterioration. This study aimed to synthesize and characterize an ascorbic acid-containing polyurethane to impart antioxidant properties to degradable scaffolds for tissue engineered heart valve (TEHV) replacement. Blends of poly(carbonate-ascorbic acid) urethane (PCAU) and poly(carbonate urethane) urea (PCUU) were fabricated into microporous scaffolds to evaluate the impact of PCAU in vitro on mechanics, degradation, cell viability, calcification, bacterial adhesion, and in vivo on native tissue response in a juvenile rat subcutaneous model. PCAU blended with PCUU in a 25:75 ratio (PCAU-25) had mechanical properties similar to PCUU, while higher concentrations of PCAU were not mechanically robust. PCAU-25 showed greater reactive oxygen species (ROS) inhibition and degradation, and reduced calcification and bacterial adhesion in vitro. In a juvenile rat subcutaneous model, both PCUU and PCAU-25 groups showed negligible calcification after 4 weeks. PCAU-25, however, showed much greater cell infiltration and immune response, possibly due to an accelerated rate of degradation. PCAU-25 was then fabricated into a polymeric valve scaffold and underwent basic mechanical and hydrodynamic performance assessment that demonstrated function similar to PCUU valves previously reported. These findings demonstrate proof-of-concept for a new polyurethane formulation incorporating ascorbic acid for antioxidant bioactivity and translatability into a functional TEHV scaffold.