Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart.
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.
Ott
Harald C
HC
Department of Surgery, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, Massachusetts 02114, USA.
Matthiesen
Thomas S
TS
Goh
Saik-Kia
SK
Black
Lauren D
LD
Kren
Stefan M
SM
Netoff
Theoden I
TI
Taylor
Doris A
DA
D000818:Animals; D021522:Bioartificial Organs; D002102:Cadaver; D042783:Endothelial Cells / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D006354:Heart, Artificial; D008297:Male; D009206:Myocardium / Q000166:cytology; D010477:Perfusion / Q000379:methods*; D051381:Rats; D011916:Rats, Inbred F344; D023822:Tissue Engineering / Q000379:methods*