Abstract 3409: Successfull Orthotopic Replacement of Aortic Heart Valves With Autologous Tissue Engineered Grafts
Introduction: Heart valve tissue engineering has a purpose to obtain a graft with improved durability compared to the routinely used valve substitutes. The aim of this study was to compare the function and morphological changes of tissue engineered (TEV) compared to cryopreserved (CPV) aortic valve (AV) allografts in an orthotopic position in sheep.
Methods and Results: Ovine AV conduits (n=5) were decellularized with detergents (0.5% sodium deoxycholate and 0.5% sodium dodecylsulfate). Autologous endothelial cells (EC) were seeded onto the valve surface and cultured under physiological conditions using high pulsatile-flow for 7 days in a bioreactor. Grafts were implanted as root with reimplantation of coronary ostia on extracorporeal circulation in sheep. Crystalloid cardioplegia and isogenic blood transfusion from previous sacrificed sheep were used. Only antiplatelet aggregation therapy was used postoperatively. CPV (n=3) were implanted as controls. The grafts were investigated for function (Echocardiography, MRI), morphological appearance, graft rejection and calcification (H&E, Von-Kossa, Pentachrome, eNOS, CD31, von Willebrand Factor, anti-perlecan, α-SMA, procollagen-I, CD45) 3 month after implantation. Decellularization led to cell-free scaffolds with preserved extracellular matrix including 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 TEV group. Explanted valves exhibited normal morphology without signs of inflammation. Scaffold was partially repopulated with interstitial autologous cells. A endothelial monolayer was covering cusps and valve sinus at 3 months. In CPV group, sporadic macroscopic calcific 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 the higher requirements of the systemic circulation in sheep. Although results of long-term experiments have to be awaited, the lack of degenerative traits makes these grafts a promising alternative for future aortic heart valve surgery.