Artifiziell hergestellte Herzklappen mittels „tissue engineering “ auf der Basis einer azellularisierten xenogenen Matrix: ln-vivo Untersuchungen im Schafmodell

Background: The ideal scaffold material for tissue engineered heart valves is discussed controversially. We evaluated acellularized xenogenic matrix constructs with and without seeding with autologous vascular cells in the pulmonary circulation in a sheep model. Methods: Porcine pulmonary valve conduits (n = 8) were acellularized by trypsin/EDTA incubation. Autologous myofibroblasts and endothelial cells were harvested from carotid arteries, xenogenic valve conduits (n = 5) were seeded first with myofibroblasts for 10 days and coated with endothelial cells for 7 days in a bioreactor, resulting in an uniform cellular restitution of the pulmonary valve conduit. Using these methods, we implanted autologous cell/xenogenic matrix constructs in 5 animals. In three control animals acellularized/ xenogenic matrix constructs were implanted. In each animal cardiopulmonary bypass was used to resect the pulmonary valve and replace it with the xenogenic valve conduits. After 6 months the animals were killed and the valves were examined histologically, and histochemically. Results: The autologous cell/xenogenic heart valves showed first signs of cusp degeneration, which resulted in functional loss of the heart valves. In comparison acellularized/xenogenic heart valves were completely repopulated by endothelial cells and myofibroblasts with preserved valvular function. In autologous cell/xenogenic heart valves a 2 to 3-fold higher population of fibroblast was observed, in contrast acellularized/ xenogenic heart valves resulted in a normal fibroblast population. Conclusion: Approaches to heart valve engineering based on acellularized/xenogenic matrices provide promising results and will hopefully led to the „ideal“ valve substitute in clinical heart valve replacement.