Annals of Biomedical Engineering

, Volume 37, Issue 4, pp 674–681

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

Article

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.

Keywords

Bioreactor Design Heart valve Tissue engineering Windkessel 

References

  1. 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, 1017–1030PubMedCrossRefGoogle Scholar
  2. 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), 906–922PubMedCrossRefGoogle Scholar
  3. 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):710–714PubMedCrossRefGoogle Scholar
  4. 4.
    Finkelstein S. M., V. R. Collins, J. N. Cohn. (1988) Arterial vascular compliance to vasodilators by Fourier and pulse contour analysis. Hypertension 12, 380–387PubMedGoogle Scholar
  5. 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), 1152–1158PubMedCrossRefGoogle Scholar
  6. 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), 1039–1049PubMedCrossRefGoogle Scholar
  7. 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 PubMedCrossRefGoogle Scholar
  8. 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. 30:646–656PubMedCrossRefGoogle Scholar
  9. 9.
    Konduri S., Y. Xing, 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), 1158–1166PubMedCrossRefGoogle Scholar
  10. 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, 1245–1256PubMedCrossRefGoogle Scholar
  11. 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, 47–52PubMedGoogle Scholar
  12. 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, 310–314PubMedCrossRefGoogle Scholar
  13. 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), 340–347PubMedCrossRefGoogle Scholar
  14. 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), 1778–1788PubMedCrossRefGoogle Scholar
  15. 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, 2004Google Scholar
  16. 16.
    Nerem R. M., D. Seliktar. (2001) Vascular tissue engineering. Annu. Rev. Biomed. Eng. 3, 225–243PubMedCrossRefGoogle Scholar
  17. 17.
    Niklason L. E., R. S. Langer. (1997) Advances in tissue engineering of blood vessels and other tissues. Transpl. Immunol. 5(4), 303–306PubMedCrossRefGoogle Scholar
  18. 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), 351–362PubMedCrossRefGoogle Scholar
  19. 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), 140–144PubMedCrossRefGoogle Scholar
  20. 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), 41–48PubMedGoogle Scholar
  21. 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. 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–H88Google Scholar
  23. 23.
    Stoclet J.-C., K. Laflamme, F. A. Auger, L. Germain. (2004) Vaisseau humains reconstitués par génie tissulaire. Med. Sci. 20(6–7), 675–678Google Scholar
  24. 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), 1083–1088PubMedCrossRefGoogle Scholar
  25. 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. 2002Google Scholar
  26. 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), 872–878PubMedCrossRefGoogle Scholar
  27. 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, 857–861PubMedCrossRefGoogle Scholar
  28. 28.
    Watt T. B., C. S. Burrus. (1976) Arterial pressure contour analysis for estimating human vascular properties. J. Appl. Physiol. 40(2), 171–176PubMedGoogle Scholar
  29. 29.
    Williams C., T. M. Wick. (2004) Perfusion bioreactor for small diameter tissue-engineered arteries. Tissue Eng. 10(5/6), 930–941PubMedCrossRefGoogle Scholar
  30. 30.
    Xing 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), 555–562PubMedCrossRefGoogle Scholar

Copyright information

© Biomedical Engineering Society 2009

Authors and Affiliations

  1. 1.Department of Mechanical EngineeringLaval UniversityQuébecCanada
  2. 2.QuébecCanada

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