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

Harald C. Ott, Thomas S. Matthiesen, Saik Kia Goh, Lauren D. Black, Stefan M. Kren, Theoden I. Netoff, Doris A. Taylor

Research output: Contribution to journalArticlepeer-review

1790 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)213-221
Number of pages9
JournalNature Medicine
Volume14
Issue number2
DOIs
StatePublished - Feb 2008

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