Orthotopic Replacement of Aortic Heart Valves with Tissue-Engineered Grafts

Aims: Heart valve tissue engineering aims to create a graft with improved durability compared to routinely used valve substitutes. This study presents the function and morphological changes of a tissue-engineered aortic valve (TEV) compared to the cryopreserved valve (CPV), aortic valve (AV) allografts in an orthotopic position in sheep. Methods and Results: Ovine AV conduits (n = 5) were decellularized with detergents. Autologous endothelial cells (ECs) were seeded onto the valve surface and cultured under physiological conditions using a high pulsatile flow. Grafts were implanted as a root with reimplantation of coronary ostia in sheep. Crystalloid cardioplegia and isogenic blood transfusions from previous sacrificed sheep were used. Only antiplatelet aggregation therapy was used postoperatively. CPVs (n = 4) served as controls. The grafts were investigated for function (echocardiography, magnetic resonance investigation), morpho/histological appearance, graft rejection, and calcification at 3 months. Decellularization led to cell-free scaffolds with preserved extracellular matrices, including the basement membrane. TEVs were covered with ECs expressing typical endothelial markers. Neither dilatation, stenosis, reductions of cusp mobility nor a significant transvalvular gradient, were observed in the TEV group. Explanted valves exhibited normal morphology without signs of inflammation. An endothelial monolayer covered cusps and the valve sinus. In the CPV group, sporadic, macroscopic, calcified degeneration with mild AV insufficiency was noted. Histology revealed signs of rejection and incipient calcification of the tissue. Conclusion: Tissue-engineered AV based on decellularized valve allografts satisfy short-term requirements of the systemic circulation in sheep. Although results of long-term experiments are pending, the lack of degenerative traits thus far, makes these grafts a promising alternative for future aortic heart valve surgery.