[A xenogeneic acellularized matrix for heart valve tissue engineering: in vivo study in a sheep model].
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=16) were acellularized by trypsin/ EDTA incubation. Autologous myofibroblasts and endothelial cells were harvested from carotid arteries; xenogenic valve conduits (n=10) were repopulated with these autologous cells resulting in uniform cellular restitution of the pulmonary valve conduit surface. Using this method, we implanted autologous cell/xenogenic matrix constructs (XB) in ten animals. In six control animals acellularized/xenogenic matrix constructs (XA) were implanted. In each animal, cardiopulmonary bypass was used to resect the pulmonary valve and replace it with the xenogenic pulmonary valve conduits. The animals were killed after 6, 9 or 12 months. The explanted valves were examined histologically and biochemically.


RESULTS
After explantation XB showed severe cusp degeneration, which resulted in severe valvular regurgitation. In comparison, XA appeared macroscopically normal with preserved valvular function. The surface of XB were covered with an incomplete endothelial multilayer. The extracellular matrix (ECM) of XB showed pathological amounts of collagenous and elastic fibers as well as proteoglycan content combined with an increase cellularity. The XA were completely repopulated by an endothelial cell monolayer; the ECM was repopulated with a myofibroblast population comparable to native ovine heart valve tissue.


CONCLUSIONS
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.
Leyh
R
R
Abteilung Thorax- Herz- und Gefässchirurgie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30623 Hannover, Germany. leyh@thg.mh-hannover.de
Wilhelmi
M
M
Haverich
A
A
Mertsching
H
H
D000818:Animals; D001705:Bioprosthesis; D002448:Cell Adhesion / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D017690:Cell Transplantation; D003094:Collagen / Q000378:metabolism; D004452:Echocardiography; D004547:Elastic Tissue / Q000473:pathology; D004730:Endothelium, Vascular / Q000166:cytology; D005109:Extracellular Matrix / Q000473:pathology; D005347:Fibroblasts / Q000166:cytology; D006350:Heart Valve Prosthesis; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D011664:Pulmonary Valve / Q000473:pathology / Q000601:surgery; D012756:Sheep; D013499:Surface Properties; D013552:Swine; D023822:Tissue Engineering / Q000379:methods*
D003094:Collagen