In vitro generation of atrioventricular heart valve neoscaffolds.
Tissue engineering of cardiovascular structures represents a novel approach to improve clinical strategies in heart valve disease treatment. The aim of this study was to engineer decellularized atrioventricular heart valve neoscaffolds with an intact ultrastructure and to reseed them with umbilical cord-derived endothelial cells under physiological conditions in a bioreactor environment. Mitral (n=38) and tricuspid (n=36) valves were harvested from 40 hearts of German Landrace swine from a selected abattoir. Decellularization of atrioventricular heart valves was achieved by a detergent-based cell extraction protocol. Evaluation of the decellularization method was conducted with light microscopy and quantitative analysis of collagen and elastin content. The presence of residual DNA within the decellularized atrioventricular heart valves was determined with spectrophotometric quantification. The described decellularization regime produced full removal of native cells while maintaining the mechanical stability and the quantitative composition of the atrioventricular heart valve neoscaffolds. The surface of the xenogeneic matrix could be successfully reseeded with in vitro-expanded human umbilical cord-derived endothelial cells under physiological flow conditions. After complete decellularization with the detergent-based protocol described here, physiological reseeding of the xenogeneic neoscaffolds resulted in the formation of a confluent layer of human umbilical cord-derived endothelial cells. These results warrant further research toward the generation of atrioventricular heart valve neoscaffolds on the basis of decellularized xenogeneic tissue.
Heart and Marfan Center, Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany; Department of Cardiothoracic Transplantation and Mechanical Circulatory Support, Royal Brompton & Harefield NHS Foundation Trust, Harefield, Middlesex, UK.
Alexander
A
Weymann
Tamás
T
Radovits
Bastian
B
Schmack
Shiliang
S
Li
Sevil
S
Korkmaz
Pál
P
Soós
Roland
R
Istók
Gabor
G
Veres
Nicole
N
Chaimow
Matthias
M
Karck
Gábor
G
Szabó
D000818:Animals; D001705:Bioprosthesis; D019149:Bioreactors; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology*; D005260:Female; D006350:Heart Valve Prosthesis; D006351:Heart Valves / Q000166:cytology / Q000648:ultrastructure; D006801:Humans; D011474:Prosthesis Design; D013552:Swine; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry*; D014470:Umbilical Cord / Q000166:cytology
Atrioventricular heart valves; Bioreactor; Decellularization; Tissue engineering