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Simplified Pulse Reactor for Real-Time Long-Term In Vitro Testing of Biological Heart Valves

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Abstract

Long-term function of biological heart valve prostheses (BHV) is limited by structural deterioration leading to failure with associated arterial hypertension. The objective of this work was development of an easy to handle real-time pulse reactor for evaluation of biological and tissue engineered heart valves under different pressures and long-term conditions. The pulse reactor was made of medical grade materials for placement in a 37 °C incubator. Heart valves were mounted in a housing disc moving horizontally in culture medium within a cylindrical culture reservoir. The microprocessor-controlled system was driven by pressure resulting in a cardiac-like cycle enabling competent opening and closing of the leaflets with adjustable pulse rates and pressures between 0.25 to 2 Hz and up to 180/80 mmHg, respectively. A custom-made imaging system with an integrated high-speed camera and image processing software allow calculation of effective orifice areas during cardiac cycle. This simple pulse reactor design allows reproducible generation of patient-like pressure conditions and data collection during long-term experiments.

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Abbreviations

BHV:

Biological heart valve prosthesis

SBF:

Simulated body fluid

EOA:

Effective orifice area

TAD:

Tissue annulus diameter

fps:

Frames per second

References

  1. Aksoy, Y., C. Yagmur, G. O. Tekin, J. Yagmur, E. Topal, E. Kekilli, H. Turhan, F. Kosar, and E. Yetkin. Aortic valve calcification: association with bone mineral density and cardiovascular risk factors. Coron. Artery Dis. 16:379–383, 2005.

    Article  PubMed  Google Scholar 

  2. Blackman, B. R., G. Garcia-Cardena, and M. A. Gimbrone, Jr. A new in vitro model to evaluate differential responses of endothelial cells to simulated arterial shear stress waveforms. J. Biomech. Eng. 124:397–407, 2002.

    Article  PubMed  Google Scholar 

  3. Burdon, T. A., D. C. Miller, P. E. Oyer, R. S. Mitchell, E. B. Stinson, V. A. Starnes, and N. E. Shumway. Durability of porcine valves at fifteen years in a representative North American patient population. J. Thorac. Cardiovasc. Surg. 103:238–251, 1992; discussion 251–232.

    CAS  PubMed  Google Scholar 

  4. Butany, J., C. Fayet, M. S. Ahluwalia, P. Blit, C. Ahn, C. Munroe, N. Israel, R. J. Cusimano, and R. L. Leask. Biological replacement heart valves. Identification and evaluation. Cardiovasc. Pathol. 12:119–139, 2003.

    Article  PubMed  Google Scholar 

  5. CEN Prop. Standard EN 120006-1. European Committee for Standardization, Brussels, Belgium, 1995.

  6. Clark, R. E., and W. M. Swanson. In vitro durability of Hancock Model 242 porcine heart valve. J. Thorac. Cardiovasc. Surg. 78:277–280, 1979.

    CAS  PubMed  Google Scholar 

  7. Deiwick, M., B. Glasmacher, E. Pettenazzo, D. Hammel, W. Castellon, G. Thiene, H. Reul, E. Berendes, and H. H. Scheld. Primary tissue failure of bioprostheses: new evidence from in vitro tests. Thorac. Cardiovasc. Surg. 49:78–83, 2001.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  9. Engelmayr, Jr., G. C., E. Rabkin, F. W. Sutherland, F. J. Schoen, J. E. Mayer, Jr., and M. S. Sacks. The independent role of cyclic flexure in the early in vitro development of an engineered heart valve tissue. Biomaterials 26:175–187, 2005.

    Article  CAS  PubMed  Google Scholar 

  10. Engelmayr, Jr., G. C., V. L. Sales, J. E. Mayer, Jr., and M. S. Sacks. Cyclic flexure and laminar flow synergistically accelerate mesenchymal stem cell-mediated engineered tissue formation: implications for engineered heart valve tissues. Biomaterials 27:6083–6095, 2006.

    Article  CAS  PubMed  Google Scholar 

  11. FDA—Replacement Heart Valve Guide. FDA, Rockland, MD, USA, 1994.

  12. Geens, J. H., S. Trenson, F. R. Rega, E. K. Verbeken, and B. P. Meyns. Ovine models for chronic heart failure. Int. J. Artif. Organs 32:496–506, 2009.

    PubMed  Google Scholar 

  13. Gerosa, G., V. Tarzia, G. Rizzoli, and T. Bottio. Small aortic annulus: the hydrodynamic performances of 5 commercially available tissue valves. J. Thorac. Cardiovasc. Surg. 131:1058–1064, 2006.

    Article  PubMed  Google Scholar 

  14. Haaf, P., M. Steiner, T. Attmann, G. Pfister, J. Cremer, and G. Lutter. A novel pulse duplicator system: evaluation of different valve prostheses. Thorac. Cardiovasc. Surg. 57:10–17, 2009.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  16. Hoerstrup, S. P., R. Sodian, S. Daebritz, J. Wang, E. A. Bacha, D. P. Martin, A. M. Moran, K. J. Guleserian, J. S. Sperling, S. Kaushal, J. P. Vacanti, F. J. Schoen, and J. E. Mayer, Jr. Functional living trileaflet heart valves grown in vitro. Circulation 102:III44–III49, 2000.

    CAS  PubMed  Google Scholar 

  17. Hoerstrup, S. P., R. Sodian, J. S. Sperling, J. P. Vacanti, and J. E. Mayer, Jr. New pulsatile bioreactor for in vitro formation of tissue engineered heart valves. Tissue Eng. 6:75–79, 2000.

    Article  CAS  PubMed  Google Scholar 

  18. ISO 5840-2005 Cardiovascular implants—cardiac valve prostheses. http://www.iso.org.

  19. Kokubo, T., and H. Takadama. How useful is SBF in predicting in vivo bone bioactivity? Biomaterials 27:2907–2915, 2006.

    Article  CAS  PubMed  Google Scholar 

  20. Lichtenberg, A., I. Tudorache, S. Cebotari, S. Ringes-Lichtenberg, G. Sturz, K. Hoeffler, C. Hurscheler, G. Brandes, A. Hilfiker, and A. Haverich. In vitro re-endothelialization of detergent decellularized heart valves under simulated physiological dynamic conditions. Biomaterials 27:4221–4229, 2006.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  22. Montarello, J. K., A. C. Perakis, E. Rosenthal, E. G. Boyd, A. K. Yates, P. B. Deverall, E. Sowton, and P. V. Curry. Normal and stenotic human aortic valve opening: in vitro assessment of orifice area changes with flow. Eur. Heart J. 11:484–491, 1990.

    CAS  PubMed  Google Scholar 

  23. Morsi, Y. S., W. W. Yang, A. Owida, and C. S. Wong. Development of a novel pulsatile bioreactor for tissue culture. J. Artif. Organs 10:109–114, 2007.

    Article  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  25. Netter, F. H. “Band 1: Herz.” In: Farbatlanten der Medizin—The Ciba Collection of Medical Illustrations, edited by M. Stauch. Stuttgart: Georg Thieme Verlag Stuttgart-New York, 1990, pp. 45.

  26. Pohl, M., M. O. Wendt, B. Koch, R. Kuhnel, O. Samba, and G. Vlastos. Model fluids of blood for in vitro testing of artificial heart valves. Z. Med. Phys. 11:187–194, 2001.

    CAS  PubMed  Google Scholar 

  27. Pohl, M., M. O. Wendt, S. Werner, B. Koch, and D. Lerche. In vitro testing of artificial heart valves: comparison between Newtonian and non-Newtonian fluids. Artif. Organs 20:37–46, 1996.

    Article  CAS  PubMed  Google Scholar 

  28. Reul, H., and K. Potthast. Durability/wear testing of heart valve substitutes. J. Heart Valve Dis. 7:151–157, 1998.

    CAS  PubMed  Google Scholar 

  29. Ruzicka, D. J., W. B. Eichinger, I. M. Hettich, S. Bleiziffer, R. Bauernschmitt, and R. Lange. Hemodynamic performance of the new St. Jude Medical Epic Supra porcine bioprosthesis in comparison to the Medtronic Mosaic on the basis of patient annulus diameter. J. Heart Valve Dis. 17:426–433, 2008; discussion 434.

    PubMed  Google Scholar 

  30. Schenke-Layland, K., F. Opitz, M. Gross, C. Doring, K. J. Halbhuber, F. Schirrmeister, T. Wahlers, and U. A. Stock. Complete dynamic repopulation of decellularized heart valves by application of defined physical signals—an in vitro study. Cardiovasc. Res. 60:497–509, 2003.

    Article  CAS  PubMed  Google Scholar 

  31. Stock, U. A., J. P. Vacanti, J. E. Mayer, Jr., and T. Wahlers. Tissue engineering of heart valves—current aspects. Thorac. Cardiovasc. Surg. 50:184–193, 2002.

    Article  CAS  PubMed  Google Scholar 

  32. Syedain, Z. H., and R. T. Tranquillo. Controlled cyclic stretch bioreactor for tissue-engineered heart valves. Biomaterials 30:4078–4084, 2009.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  34. Werner, S., M. O. Wendt, K. Schichl, M. Pohl, and B. Koch. Testing the hydrodynamic properties of heart valve prostheses with a new test apparatus. Biomed. Tech. (Berl) 39:204–210, 1994.

    Article  CAS  Google Scholar 

  35. Weston, M. W., and A. P. Yoganathan. Biosynthetic activity in heart valve leaflets in response to in vitro flow environments. Ann. Biomed. Eng. 29:752–763, 2001.

    Article  CAS  PubMed  Google Scholar 

  36. Xing, Y., Z. He, J. N. Warnock, S. L. Hilbert, and A. P. Yoganathan. Effects of constant static pressure on the biological properties of porcine aortic valve leaflets. Ann. Biomed. Eng. 32:555–562, 2004.

    Article  PubMed  Google Scholar 

  37. Yacoub, M. H., and J. J. Takkenberg. Will heart valve tissue engineering change the world? Nat. Clin. Pract. Cardiovasc. Med. 2:60–61, 2005.

    Article  CAS  PubMed  Google Scholar 

  38. Yoganathan, A. P., Z. He, and S. Casey Jones. Fluid mechanics of heart valves. Annu. Rev. Biomed. Eng. 6:331–362, 2004.

    Article  CAS  PubMed  Google Scholar 

  39. Zapanta, C. M., E. G. Liszka, Jr., T. C. Lamson, D. R. Stinebring, S. Deutsch, D. B. Geselowitz, and J. M. Tarbell. A method for real-time in vitro observation of cavitation on prosthetic heart valves. J. Biomech. Eng. 116:460–468, 1994.

    Article  CAS  PubMed  Google Scholar 

  40. Zeltinger, J., L. K. Landeen, H. G. Alexander, I. D. Kidd, and B. Sibanda. Development and characterization of tissue-engineered aortic valves. Tissue Eng. 7:9–22, 2001.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by a grant from the German Research Council (Deutsche Forschungsgemeinschaft) Sto 359/2-3, Sto 359/4-1 (U.A.S.), Sche701/2-1, Sche701/3-1 8 (S-L.K) and German Federal Institute for Risk Assessment (BFR-ZEBET) (U.A.S.).

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Authors and Affiliations

  1. Department of Thoracic, Cardiac and Vascular Surgery, University Hospital Tübingen, Hoppe-Seyler-Strasse 3, 72076, Tübingen, Germany

    Martina Schleicher, Olaf Fritze, Agnes J. Huber & Ulrich A. Stock

  2. Department of Central Engineering, Friedrich-Schiller-University, Jena, Germany

    Günther Sammler & Günter Ditze

  3. Realtime Imaging, Berlin, Germany

    Michael Schmauder

  4. Department of Medicine/Cardiology, Cardiovascular Research Laboratory, UCLA, Los Angeles, CA, USA

    Katja Schenke-Layland

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  1. Martina Schleicher
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  2. Günther Sammler
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Correspondence to Ulrich A. Stock.

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Associate Editor Jane Grande-Allen oversaw the review of this article.

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Schleicher, M., Sammler, G., Schmauder, M. et al. Simplified Pulse Reactor for Real-Time Long-Term In Vitro Testing of Biological Heart Valves. Ann Biomed Eng 38, 1919–1927 (2010). https://doi.org/10.1007/s10439-010-9975-8

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  • DOI: https://doi.org/10.1007/s10439-010-9975-8

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