Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart (2025)

  • Technical Report
  • Published:
  • Harald C Ott1,
  • Thomas S Matthiesen2,
  • Saik-Kia Goh2,
  • Lauren D Black3,
  • Stefan M Kren2,
  • Theoden I Netoff3 &
  • Doris A Taylor2,4

Nature Medicine volume14,pages 213–221 (2008)Cite this article

  • 48k Accesses

  • 2093 Citations

  • 127 Altmetric

  • Metrics details

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.

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Change institution

Buy or subscribe

Subscribe to this journal

Receive 12 print issues and online access

$209.00 per year

only $17.42 per issue

Learn more

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF

Prices may be subject to local taxes which are calculated during checkout

Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart (1)
Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart (2)
Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart (3)
Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart (4)
Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart (5)

Similar content being viewed by others

Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart (6)

Interindividual heterogeneity affects the outcome of human cardiac tissue decellularization

Article Open access 21 October 2021

Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart (8)

Challenges and opportunities for the next generation of cardiovascular tissue engineering

Article 05 September 2022

References

  1. Kobashigawa, J.A. & Patel, J.K. Immunosuppression for heart transplantation: where are we now? Nat. Clin. Pract. Cardiovasc. Med. 3, 203–212 (2006).

    Article CAS PubMed Google Scholar

  2. Eschenhagen, T. & Zimmermann, W.H. Engineering myocardial tissue. Circ. Res. 97, 1220–1231 (2005).

    Article CAS PubMed Google Scholar

  3. Zimmermann, W.H. et al. Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat hearts. Nat. Med. 12, 452–458 (2006).

    Article CAS PubMed Google Scholar

  4. Sekine, H., Shimizu, T., Kosaka, S., Kobayashi, E. & Okano, T. Cardiomyocyte bridging between hearts and bioengineered myocardial tissues with mesenchymal transition of mesothelial cells. J. Heart Lung Transplant. 25, 324–332 (2006).

    Article PubMed Google Scholar

  5. Robinson, K.A. et al. Extracellular matrix scaffold for cardiac repair. Circulation 112, I135–I143 (2005).

    Article PubMed Google Scholar

  6. Radisic, M., Deen, W., Langer, R. & Vunjak-Novakovic, G. Mathematical model of oxygen distribution in engineered cardiac tissue with parallel channel array perfused with culture medium containing oxygen carriers. Am. J. Physiol. Heart Circ. Physiol. 288, H1278–H1289 (2005).

    Article CAS PubMed Google Scholar

  7. Furuta, A. et al. Pulsatile cardiac tissue grafts using a novel three-dimensional cell sheet manipulation technique functionally integrates with the host heart, in vivo. Circ. Res. 98, 705–712 (2006).

    Article CAS PubMed Google Scholar

  8. Miyagawa, S. et al. Tissue cardiomyoplasty using bioengineered contractile cardiomyocyte sheets to repair damaged myocardium: their integration with recipient myocardium. Transplantation 80, 1586–1595 (2005).

    Article CAS PubMed Google Scholar

  9. Park, H., Radisic, M., Lim, J.O., Chang, B.H. & Vunjak-Novakovic, G. A novel composite scaffold for cardiac tissue engineering. In Vitro Cell. Dev. Biol. Anim. 41, 188–196 (2005).

    Article CAS PubMed Google Scholar

  10. Dellgren, G., Eriksson, M.J., Brodin, L.A. & Radegran, K. Eleven years' experience with the Biocor stentless aortic bioprosthesis: clinical and hemodynamic follow-up with long-term relative survival rate. Eur. J. Cardiothorac. Surg. 22, 912–921 (2002).

    Article PubMed Google Scholar

  11. Rieder, E. et al. Decellularization protocols of porcine heart valves differ importantly in efficiency of cell removal and susceptibility of the matrix to recellularization with human vascular cells. J. Thorac. Cardiovasc. Surg. 127, 399–405 (2004).

    Article PubMed Google Scholar

  12. Ketchedjian, A. et al. Recellularization of decellularized allograft scaffolds in ovine great vessel reconstructions. Ann. Thorac. Surg. 79, 888–896 (2005).

    Article PubMed Google Scholar

  13. Chen, R.N., Ho, H.O., Tsai, Y.T. & Sheu, M.T. Process development of an acellular dermal matrix (ADM) for biomedical applications. Biomaterials 25, 2679–2686 (2004).

    Article CAS PubMed Google Scholar

  14. Gilbert, T.W., Sellaro, T.L. & Badylak, S.F. Decellularization of tissues and organs. Biomaterials 27, 3675–3683 (2006).

    CAS PubMed Google Scholar

  15. Gerecht-Nir, S. et al. Biophysical regulation during cardiac development and application to tissue engineering. Int. J. Dev. Biol. 50, 233–243 (2006).

    Article PubMed Google Scholar

  16. Ossipow, V., Laemmli, U.K. & Schibler, U. A simple method to renature DNA-binding proteins separated by SDS-polyacrylamide gel electrophoresis. Nucleic Acids Res. 21, 6040–6041 (1993).

    Article CAS PubMed PubMed Central Google Scholar

  17. Paszek, M.J. et al. Tensional homeostasis and the malignant phenotype. Cancer Cell 8, 241–254 (2005).

    Article CAS PubMed Google Scholar

  18. Johnson, P., Maxwell, D.J., Tynan, M.J. & Allan, L.D. Intracardiac pressures in the human fetus. Heart 84, 59–63 (2000).

    Article CAS PubMed PubMed Central Google Scholar

  19. Roy, S., Silacci, P. & Stergiopulos, N. Biomechanical properties of decellularized porcine common carotid arteries. Am. J. Physiol. Heart Circ. Physiol. 289, H1567–H1576 (2005).

    Article CAS PubMed Google Scholar

  20. Courtman, D.W. et al. Development of a pericardial acellular matrix biomaterial: biochemical and mechanical effects of cell extraction. J. Biomed. Mater. Res. 28, 655–666 (1994).

    Article CAS PubMed Google Scholar

  21. Mirsadraee, S. et al. Development and characterization of an acellular human pericardial matrix for tissue engineering. Tissue Eng. 12, 763–773 (2006).

    Article CAS PubMed Google Scholar

  22. Bodnar, E., Olsen, E.G., Florio, R. & Dobrin, J. Damage of porcine aortic valve tissue caused by the surfactant sodiumdodecylsulphate. Thorac. Cardiovasc. Surg. 34, 82–85 (1986).

    Article CAS PubMed Google Scholar

  23. Grabow, N. et al. Mechanical and structural properties of a novel hybrid heart valve scaffold for tissue engineering. Artif. Organs 28, 971–979 (2004).

    Article CAS PubMed Google Scholar

  24. Russ, J. The Image Processing Handbook Ch 4. (CRC Press, London, 2002).

    Google Scholar

  25. Press, W.H., Teukolsky, S.A., Vetterling, W.T. & Flannery, B.P. in Numerical Recipies in C: The Art of Scientific Computing Ch. 12 (Cambridge University Press, Cambridge, UK, 1992).

    Google Scholar

  26. Ono, K. & Lindsey, E.S. Improved technique of heart transplantation in rats. J. Thorac. Cardiovasc. Surg. 57, 225–229 (1969).

    CAS PubMed Google Scholar

Download references

Acknowledgements

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.

Author information

Authors and Affiliations

  1. Department of Surgery, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, 02114, Massachusetts, USA

    Harald C Ott

  2. Center for Cardiovascular Repair, University of Minnesota, 312 Church Street Southeast, 7-105A NHH, Minneapolis, 55455, Minnesota, USA

    Thomas S Matthiesen,Saik-Kia Goh,Stefan M Kren&Doris A Taylor

  3. Department of Biomedical Engineering, University of Minnesota, 312 Church Street Southeast, 7 NHH, Minneapolis, 55455, Minnesota, USA

    Lauren D Black&Theoden I Netoff

  4. Department of Integrative Biology and Physiology, University of Minnesota, 6-125 Jackson Hall, 312 Church Street Southeast, Minneapolis, 55455, Minnesota, USA

    Doris A Taylor

Authors

  1. Harald C Ott

    View author publications

    You can also search for this author in PubMedGoogle Scholar

  2. Thomas S Matthiesen

    View author publications

    You can also search for this author in PubMedGoogle Scholar

  3. Saik-Kia Goh

    View author publications

    You can also search for this author in PubMedGoogle Scholar

  4. Lauren D Black

    View author publications

    You can also search for this author in PubMedGoogle Scholar

  5. Stefan M Kren

    View author publications

    You can also search for this author in PubMedGoogle Scholar

  6. Theoden I Netoff

    View author publications

    You can also search for this author in PubMedGoogle Scholar

  7. Doris A Taylor

    View author publications

    You can also search for this author in PubMedGoogle Scholar

Contributions

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)

Rights and permissions

About this article

Cite this article

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). https://doi.org/10.1038/nm1684

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nm1684

This article is cited by

Access through your institution

Change institution

Buy or subscribe

Associated content

Perfusion decellularization of whole organs

  • Jacques P Guyette
  • Sarah E Gilpin
  • Harald C Ott

Nature Protocols Protocol

Advertisement

Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart (2025)
Top Articles
Latest Posts
Recommended Articles
Article information

Author: Aron Pacocha

Last Updated:

Views: 6423

Rating: 4.8 / 5 (68 voted)

Reviews: 83% of readers found this page helpful

Author information

Name: Aron Pacocha

Birthday: 1999-08-12

Address: 3808 Moen Corner, Gorczanyport, FL 67364-2074

Phone: +393457723392

Job: Retail Consultant

Hobby: Jewelry making, Cooking, Gaming, Reading, Juggling, Cabaret, Origami

Introduction: My name is Aron Pacocha, I am a happy, tasty, innocent, proud, talented, courageous, magnificent person who loves writing and wants to share my knowledge and understanding with you.