Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart

• Published in: Nature medicine Vol. 14; no. 2; pp. 213 - 221
• Main Authors: Taylor, Doris A, Ott, Harald C, Matthiesen, Thomas S, Goh, Saik-Kia, Black, Lauren D, Kren, Stefan M, Netoff, Theoden I
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.02.2008
• Subjects: Animals; Bioartificial Organs; Biomedical materials; Biomedical research; Bioreactors; Cadaver; Cardiac patients; Care and treatment; Cellular biology; Complications and side effects; Congestive heart failure; Detergents; Donation of organs, tissues, etc; Electrical stimuli; Endothelial cells; Endothelial Cells - metabolism; Extracellular matrix; Extracellular Matrix - metabolism; Fetuses; Health aspects; Heart; Heart failure; Heart function; Heart transplantation; Heart, Artificial; Heart, Mechanical; Male; Management; Myocardium - cytology; Patient outcomes; Perfusion; Perfusion - methods; Physiological aspects; Physiology; Rats; Rats, Inbred F344; Tissue engineering; Tissue Engineering - methods; Transplantation; Ventricle; United States
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/nm1684

About 3,000 individuals in the United States are awaiting a donor heart; worldwide, 22 million individuals are living with heart failure. A bioartificial heart is a theoretical alternative to transplantation or mechanical left ventricular support. Generating a bioartificial heart requires engineering of cardiac architecture, appropriate cellular constituents and pump function. We decellularized hearts by coronary perfusion with detergents, preserved the underlying extracellular matrix, and produced an acellular, perfusable vascular architecture, competent acellular valves and intact chamber geometry. To mimic cardiac cell composition, we reseeded these constructs with cardiac or endothelial cells. To establish function, we maintained eight constructs for up to 28 d by coronary perfusion in a bioreactor that simulated cardiac physiology. By day 4, we observed macroscopic contractions. By day 8, under physiological load and electrical stimulation, constructs could generate pump function (equivalent to about 2% of adult or 25% of 16-week fetal heart function) in a modified working heart preparation.