SpringerLink
Log in

A New Bioreactor for the Development of Tissue-Engineered Heart Valves

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

This paper reports the design, manufacturing, and characterization of a new bioreactor dedicated to the development of tissue-engineered heart valve substitutes. First, a comprehensive review of the state of the art in bioreactors is presented and a rigorous classification is put forward. The existing bioreactors found in literature are organized in three groups and discussed with respect to their quality of reproduction compared to the physiological environment. The bioreactor architecture is then decomposed into basic components which may be grouped together in different arrangements, and the well-known Windkessel approach is used to study the global behavior of the system. Then, the new design, which is based on a synthesis of the features of the most evolved systems as well as on new improvements, is explained in detail. Optimal fluid dynamics are obtained with the presented bioreactor through carefully designed components and an advanced computer-controlled actuator. This allows a very accurate reproduction of physiological parameters, namely the pulsating flow rate and pressure. Finally, experimental results of flow rate and pressure waveforms are presented, where an excellent correlation with physiological measurements can be observed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Barron V., E. Lyons, C. Stenson-Cox, P. E. McHugh, A. Pandit (2003) Bioreactors for cardiovascular cell and tissue growth: a review. Ann. Biomed. Eng. 31, 1017–1030

    Article  PubMed  CAS  Google Scholar 

  2. Bilodeau K., F. Couet, F. Boccafoschi, D. Mantovani. (2005) Design of a perfusion bioreactor specific to the regeneration of vascular tissue under mechanical stresses. Artif. Organs 29(11), 906–922

    Article  PubMed  Google Scholar 

  3. Dumont K., J. Yperman, E. Verbeken, P. Segers, B. Meuris, S. Vandenberghe, W. Flameng, P. R. Verdonck (2002) Design of a new pulsatile bioreactor for tissue-engineered aortic heart valve formation. Artif. Organs 26(8):710–714

    Article  PubMed  Google Scholar 

  4. Finkelstein S. M., V. R. Collins, J. N. Cohn. (1988) Arterial vascular compliance to vasodilators by Fourier and pulse contour analysis. Hypertension 12, 380–387

    PubMed  CAS  Google Scholar 

  5. Hammermeister K., G. K. Sethi, W. G. Henderson, F. L. Grover, C. Oprian, S. H. Rahimtoola. (2000) Outcomes 15 years after valve replacement with a mechanical versus a bioprosthetic valve: final report of the veterans affairs randomized trial. J. Am. Coll. Cardiol. 36(4), 1152–1158

    Article  PubMed  CAS  Google Scholar 

  6. Hildebrand D. K., Z. J. Wu, J. E. Mayer Jr., M. S. Sacks. (2004) Design and hydrodynamic evaluation of a novel pulsatile bioreactor for biologically active heart valves. Ann. Biomed. Eng. 32(8), 1039–1049

    Article  PubMed  Google Scholar 

  7. Hoerstrup S. P., G. Zünd, R. Sodian, A. M. Schnell, J. Grünenfelder, M. I. Turina. (2001) Tissue engineering of small caliber vascular grafts. Eur. J. Cardio-Thorac. Surg. 20(1), 164–169

    Article  PubMed  CAS  Google Scholar 

  8. Hsiai T. K., S. K. Cho, H. M. Honda, S. Hama, M. Navab, L. L. Demer, C.-M. Ho. (2002) Endothelial cell dynamics under pulsating flows: significance of high versus low shear stress slew rates (δT/δt). Ann. Biomed. Eng. 30:646–656

    Article  PubMed  Google Scholar 

  9. Konduri S., Y. **ng, J. N. Warnock, Z. He, A. P. Yoganathan (2005) Normal physiological conditions maintain the biological characteristics of porcine aortic heart valves: an ex vivo organ culture study. Ann. Biomed. Eng. 33(9), 1158–1166

    Article  PubMed  Google Scholar 

  10. Laflamme K., C. J. Roberge, G. Grenier, M. Rémy-Zolghadri, S. Pouliot, K. Baker, R. Labbé, P. D’Orléans-Juste, F. A. Auger, L. Germain. (2006) Adventitia contribution in vascular tone: insights from adventitia-derived cells in a tissue-engineered human blood vessel. FASEB J. 20, 1245–1256

    Article  PubMed  CAS  Google Scholar 

  11. L’Heureux N., S. Pâquet, R. Labbé, L. Germain, F. A. Auger. (1998) A completely biological tissue-engineered human blood vessel. FASEB J. 12, 47–52

    PubMed  CAS  Google Scholar 

  12. Lueders C., R. Sodian, M. Shakibaei, R. Hetzer. (2006) Short-term culture of human neonatal myofibroblasts seeded using a novel three-dimensional rotary seeding device. ASAIO J. 52, 310–314

    Article  PubMed  Google Scholar 

  13. Mironov V., V. Kasyanov, K. McAllister, S. Oliver, J. Sistino, R. Markwald (2003) Perfusion bioreactor for vascular tissue engineering with capacities for longitudinal stretch. J. Craniofac. Surg. 14(3), 340–347

    Article  PubMed  Google Scholar 

  14. Mol A., N. J. B. Driessen, M. C. M. Rutten, S. P. Hoerstrup, C. V. C. Bouten, F. P. T. Baaijens (2005) Tissue engineering of human heart valve leaflets: a novel bioreactor for a strain-based conditioning approach. Ann. Biomed. Eng. 33(12), 1778–1788

    Article  PubMed  Google Scholar 

  15. Narita, Y., K.-I. Hata, H. Kagami, A. Usui, M. Ueda, and Y. Ueda. Novel pulse duplicating bioreactor system for tissue-engineered vascular construct. Tissue Eng. 10(7/8):1224–1233, 2004

    Google Scholar 

  16. Nerem R. M., D. Seliktar. (2001) Vascular tissue engineering. Annu. Rev. Biomed. Eng. 3, 225–243

    Article  PubMed  CAS  Google Scholar 

  17. Niklason L. E., R. S. Langer. (1997) Advances in tissue engineering of blood vessels and other tissues. Transpl. Immunol. 5(4), 303–306

    Article  PubMed  CAS  Google Scholar 

  18. Seliktar D., R. A. Black, R. P. Vito, R. M. Nerem. (2000) Dynamic mechanical conditioning of collagen-gel blood vessel constructs induces remodelling in vitro. Ann. Biomed. Eng. 28(4), 351–362

    Article  PubMed  CAS  Google Scholar 

  19. Sodian R., S. P. Hoerstrup, J. S. Sperling, S. H. Daebritz, D. P. Martin, F. J. Schoen, J. P. Vacanti, J. E. Mayer Jr. (2000) Tissue engineering of heart valves: in vitro experiences. Ann. Thorac. Surg. 70(1), 140–144

    Article  PubMed  CAS  Google Scholar 

  20. Smith J. D., N. Davies, A. I. Willis, B. E. Sumpio, P. Zilla. (2001) Cyclic stretch induces the expression of vascular endothelial growth factor in vascular smooth muscle cells. Endothelium 8(1), 41–48

    PubMed  CAS  Google Scholar 

  21. Statistical Fact Sheet––Populations 2008 update international cardiovascular disease statistics, American Heart Association. http://www.americanheart.org/presenter.jhtml?identifier=3001008, June 6th, 2007

  22. Stergiopulos N., B. E. Westerhof, N. Westerhof (1999) Total arterial inertance as the fourth element of the Windkessel model. Am. J. Physiol. 99, H81–H88

    Google Scholar 

  23. Stoclet J.-C., K. Laflamme, F. A. Auger, L. Germain. (2004) Vaisseau humains reconstitués par génie tissulaire. Med. Sci. 20(6–7), 675–678

    Google Scholar 

  24. Thompson C. A., P. Colon-Hernandez, I. Pomerantseva, B. D. MacNeil, B. Nasseri, J. P. Vacanti, S. N. Oesterle (2002) A novel pulsatile, laminar flow bioreactor for the development of tissue-engineered vascular structures. Tissue Eng. 8(6), 1083–1088

    Article  PubMed  CAS  Google Scholar 

  25. Tsiagkli, S., and T. M. Wick. Dynamic seeding of tissue-engineered vascular grafts in a novel perfusion bioreactor system. Department of Biomedical Engineering, Georgia Institute of Technology. Proceedings of the Second Joint EMBS/BMES Conference Houston. 2002

  26. Verdonck P. R., K. Dumont, P. Segers, S. Vandenberghe, G. V. Nooten. (2002) Mock loop testing of On-X prosthetic mitral valve with Doppler echocardiography. Artif. Organs 26(10), 872–878

    Article  PubMed  Google Scholar 

  27. Warnock J. N., S. Konduri, Z. He, A. P. Yoganathan. (2005) Design of a sterile organ culture system for the ex vivo study of aortic heart valves. J. Biomech. Eng. 127, 857–861

    Article  PubMed  Google Scholar 

  28. Watt T. B., C. S. Burrus. (1976) Arterial pressure contour analysis for estimating human vascular properties. J. Appl. Physiol. 40(2), 171–176

    PubMed  Google Scholar 

  29. Williams C., T. M. Wick. (2004) Perfusion bioreactor for small diameter tissue-engineered arteries. Tissue Eng. 10(5/6), 930–941

    Article  PubMed  CAS  Google Scholar 

  30. **ng Y., Z. He, J. N. Warnock, S. L. Hilbert, A. P. Yoganathan. (2004) Effects of constant static pressure on the biological properties of porcine heart valve leaflets. Ann. Biomed. Eng. 32(4), 555–562

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We wish to thank our great team of collaborators: Yvan Maciel, professor at Laval University’s Department of Mechanical Engineering, Dr François Auger and Dr Lucie Germain, professors at Laval University’s Department of Surgery, and Dan Lacroix, project manager at the LOEX research center (St-Sacrement Hospital) in Quebec. We also wish to thank Rosalie Pelletier and Catherine Tremblay, M.Sc. students, for their support and contribution to this work.

Author information

Authors and Affiliations

  1. Department of Mechanical Engineering, Laval University, Québec, QC, Canada

    Jean Ruel & Geneviève Lachance

  2. 1026 avenue de la Médecine, Pavillon Adrien-Pouliot, office 1361, Québec, PQ, GIV 0A6, Canada

    Jean Ruel

Authors
  1. Jean Ruel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Geneviève Lachance
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jean Ruel.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ruel, J., Lachance, G. A New Bioreactor for the Development of Tissue-Engineered Heart Valves. Ann Biomed Eng 37, 674–681 (2009). https://doi.org/10.1007/s10439-009-9646-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-009-9646-9

Keywords

Search

Navigation