Characterization of resolvable polymers used for developing in utero fetal valve replacements

Abstract

Patients with single ventricle diseases (SVD) are often treated with palliative surgeries but, fetal valvuloplasty experience suggests a subgroup of flow dependent SVDs arise from valvular stenosis. Hypothetically, fetal endovascular valve replacement could restore flow and reverse hypoplasia, providing the individual with a living neovalve, if a tissue-engineered heart valve (TEHV) were used. This study aims to optimize the design of TEHV polymeric valves for in utero implantation.

N=3 stent designs with Polycaprolactone (PCL) and Poly-l-lactic acid (PLLA) used as stent materials were simulated computationally. Stress distributions and deformation parameters were studied. N=2 PCL prototypes were manufactured using established methods and degraded in a 2M sodium hydroxide (NaOH) solution. Leaflet samples were analyzed every 2.5h, 4h, 18h, and 24hours to measure weight loss and degraded regions through biaxial testing and microscopic analysis using scanning electron microscopy. One prototype with a metal stent was tested in the accelerated wear tester (AWT).

Overall, both polymers had good performance characteristics, especially PLLA, and less potential for distortion with good radial expansion. Degradation of the prototype began at leaflet commissures, with only the skirt remaining intact after 72 hours. Total mass loss was 45% (±4%). Biaxial testing showed peak stiffness at 4 hours and a loss of mechanical properties in 0.75% PCL over time. Ongoing microscopic analyses will supplement this work. The prototype sustained 17 million cycles in the AWT. This study will provide further insight into engineering design considerations of a bioresorbable fetal heart valve replacement.