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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.

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Figure 1: Perfusion decellularization of whole rat hearts.
Figure 2: Composition and characteristics of decellularized rat heart tissue.
Figure 3: Vascular architecture of decellularized rat heart tissue.
Figure 4: Formation of a working perfused bioartificial heart-like construct by recellularization of decellularized cardiac ECM.
Figure 5: Histological analysis of recellularized rat heart constructs.

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We thank S. Keirstead and D. Lowe for access to electromechanical stimulation equipment and guidance; J. Sedgewick and J. Oja of the Biomedical Image Processing Laboratory at the University of Minnesota, Minneapolis, for access to photographic equipment and technical support; and the staff of the University of Minnesota CharFac facility, especially A. Ressler, for TEM assistance. This study was supported by a Faculty Research Development Grant to H.C.O. and D.A.T. from the Academic Health Center, University of Minnesota, Minneapolis, and by funding from the Center for Cardiovascular Repair, University of Minnesota, and the Medtronic Foundation to D.A.T.

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Authors and Affiliations



H.C.O. and D.A.T. conceived, designed and oversaw all of the studies, collection of results, interpretation of data and writing of the manuscript. H.C.O. was responsible for the primary undertaking, completion and supervision of all studies during his tenure at the University of Minnesota. T.S.M. designed and implemented the bioreactor studies along with H.C.O., participated in the mechanical testing studies and was instrumental in data and figure preparation for the final manuscript. S.-K.G. performed most of the immunohistochemistry and staining, except for the re-endothelialized tissues. L.D.B. performed the mechanical testing. S.M.K. decellularized the hearts, performed all surgeries and re-endothelialization experiments, and participated in the bioreactor studies. T.I.N. performed the motion analysis of the movies.

Corresponding author

Correspondence to Doris A Taylor.

Supplementary information

Supplementary Text and Figures

Supplementary Figs. 1–3 (PDF 1965 kb)

Supplementary Movie 1

Heterotopic transplant of decellularized rat heart into RNU rat abdomen. (MOV 1168 kb)

Supplementary Movie 2

Recellularization of decellularized heart tissue sections with neonatal cardiomyocytes. (MOV 544 kb)

Supplementary Movie 3

Recellularized heart construct with an estimate of wall movement on day 4. (MOV 816 kb)

Supplementary Movie 4

Recellularized heart construct with an estimate of wall movement on day 4. (MOV 1113 kb)

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Ott, H., Matthiesen, T., Goh, SK. et al. Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart. Nat Med 14, 213–221 (2008).

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