Endothelialization of heart valve matrix using a computer-assisted pulsatile bioreactor.
Although calcification remains as the main clinical concern associated with bioprosthetic heart valve replacement surgery, there is evidence that tissue deterioration leads to thromboembolism. In such instances, measures that prevent thrombosis may be beneficial. To minimize thrombosis, endothelialization of the valve surface before implantation has been proposed to facilitate coverage. In this study we aimed to define the optimal flow parameters for the endothelialization of decellularized heart valves using endothelial progenitor cell (EPC)-derived endothelial cells (ECs). We assessed the thrombogenic characteristics of the endothelialized heart valve surface using a bioreactor. EPC-derived ECs were seeded on decellularized porcine valve scaffolds. A computer-controlled bioreactor system was used to determine the optimal flow rates. Successful endothelialization was achieved by preconditioning the cell-seeded valves with stepwise increases in volume flow rate up to 2 L/min for 7 days. We show that decellularized valve scaffolds seeded with EPC-derived ECs improved the anti-thrombotic properties of the valve, whereas the scaffolds without ECs escalated the coagulation process. This study demonstrates that preconditioning of ECs seeded on valve matrices using a bioreactor system is necessary for achieving uniform endothelialization of valve scaffolds, which may reduce thrombotic activity after implantation in vivo.
Lee
Dong Joon
DJ
Wake Forest Institute for Regenerative Medicine, Winston-Salem, North Carolina, USA.
Steen
Julie
J
Jordan
James E
JE
Kincaid
Edward H
EH
Kon
Neal D
ND
Atala
Anthony
A
Berry
Joel
J
Yoo
James J
JJ