Improved geometry of decellularized tissue engineered heart valves to prevent leaflet retraction

Recent studies on decellularized tissue engineered heart valves (DTEHVs) showed rapid host cell repopulation and increased valvular insufficiency developing over time, associated with leaflet shortening. A possible explanation for this result was found using computational simulations, which revealed radial leaflet compression in the original valvular geometry when subjected to physiological pressure conditions. Therefore, an improved geometry was suggested to enable radial leaflet extension to counteract for host cell mediated retraction. In this study, we propose a solution to impose this new geometry by using a constraining bioreactor insert during culture. Human cell based DTEHVs (n = 5) were produced as such, resulting in an enlarged coaptation area and profound belly curvature. Extracellular matrix was homogeneously distributed, with circumferential collagen alignment in the coaptation region and global tissue anisotropy. Based on in vitro functionality experiments, these DTEHVs showed competent hydrodynamic functionality under physiological pulmonary conditions and were fatigue resistant, with stable functionality up to 16 weeks in vivo simulation. Based on implemented mechanical data, our computational models revealed a considerable decrease in radial tissue compression with the obtained geometrical adjustments. Therefore, these improved DTEHV are expected to be less prone to host cell mediated leaflet retraction and will remain competent after implantation

Tissue-Engineered Heart Valves

A tissue engineered heart valve (TEHV) could serve as a living, implantable valve replacement that would grow and adapt with the patient. A TEHV consists of relevant cells seeded on or entrapped in a scaffold material which is designed to degrade as the cells produce their own extracellular matrix components. Because the valve consists of living tissue, it can grow and remodel as a patient ages, making it an especially attractive replacement option for pediatric and young adult patients. To date, using various cell sources, scaffold materials, and/or in vitro culture protocols, several laboratories have produced TEHVs with the appropriate geometry and near-native mechanical properties. TEHVs implanted in the pulmonary position in sheep in our laboratory have shown promising short-term functionality but fail to maintain good performance after several months in vivo. Upcoming TEHV research will focus on optimization of TEHV components and in vitro culture conditions in order to improve long-term function post-implant, with the hope of performing human implants in the future