Skip to main content
SpringerLink
Log in

The Intrinsic Fatigue Mechanism of the Porcine Aortic Valve Extracellular Matrix

  • Published:
Cardiovascular Engineering and Technology Aims and scope Submit manuscript

Abstract

Decellularized aortic valves (AV) are promising scaffolds for tissue engineered heart valve (TEHV) application; however, it is not known what the intrinsic fatigue mechanism of the AV extracellular matrix (ECM) is and how this relates to decellularized AV functional limits when tissue remodeling does not take place. In this study, decellularized AVs were subjected to in vitro cardiac exercising and the exercised leaflets were characterized to assess the structural and mechanical alterations. A flow-loop cardiac exerciser was designed to allow for pulsatile flow conditions while maintaining sterility. The acellular valve conduits were sutured into a silicone root with the Valsalva sinus design and subjected to cardiac cycling for 2 weeks (1.0 million cycles) and 4 weeks (2.0 million cycles). Following exercising, thorough structural and mechanical characterizations were then performed. The overall morphology was maintained and the exercised leaflets were able to coapt and support load; however, the leaflets exhibited an unfolded and thinned morphology. The straightening of the locally wavy collagen fiber structure was confirmed by histology and small angle light scattering; the disruption of elastin network was also observed. Biaxial mechanical testing showed that the leaflet extensibility was largely reduced by cardiac exercising. In the absence of cellular maintenance, decellularized leaflets experience structural fatigue due to lack of exogenous stabilizing crosslinks, and the structural disruption is irreversible and cumulative. Although not being a means to predict the durability of the acellular valve implants, this mechanistic study reveals the fatigue pattern of the acellular leaflets and implies the importance of recellularization in developing a TEHV, in which long term durability will likely be better achieved by continual remodeling and repair of the valvular ECM.

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

Access this article

Log in via an institution

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
Figure 5
Figure 6
Figure 7
Figure 8

Similar content being viewed by others

References

  1. Angell, W. W., J. H. Oury, C. G. Duran, and C. Infantes-Alcon. Twenty-year comparison of the human allograft and porcine xenograft. Ann. Thorac. Surg. 48(3 Suppl):S89–S90, 1989.

    Article  Google Scholar 

  2. Bader, A., T. Schilling, O. E. Teebken, G. Brandes, T. Herden, G. Steinhoff, et al. Tissue engineering of heart valves—human endothelial cell seeding of detergent acellularized porcine valves. Eur. J. Cardiothorac. Surg. 14(3):279–284, 1998.

    Article  Google Scholar 

  3. Bertipaglia, B., F. Ortolani, L. Petrelli, G. Gerosa, M. Spina, P. Pauletto, et al. Cell characterization of porcine aortic valve and decellularized leaflets repopulated with aortic valve interstitial cells: the VESALIO Project (Vitalitate Exornatum Succedaneum Aorticum Labore Ingenioso Obtenibitur). Ann. Thorac. Surg. 75(4):1274–1282, 2003.

    Article  Google Scholar 

  4. Booth, C., S. A. Korossis, H. E. Wilcox, K. G. Watterson, J. N. Kearney, J. Fisher, et al. Tissue engineering of cardiac valve prostheses I: development and histological characterization of an acellular porcine scaffold. J. Heart Valve Dis. 11(4):457–462, 2002.

    Google Scholar 

  5. Cannegieter, S., F. Rosendaal, and E. Briet. Thromboembolic and bleeding complications in patients with mechanical heart valve prostheses. Circulation 89:635–641, 1994.

    Google Scholar 

  6. Cebotari, S., H. Mertsching, K. Kallenbach, S. Kostin, O. Repin, A. Batrinac, et al. Construction of autologous human heart valves based on an acellular allograft matrix. Circulation 106(12 Suppl 1):I63–I68, 2002.

    Google Scholar 

  7. Courtman, D. W., C. A. Pereira, S. Omar, S. E. Langdon, J. M. Lee, and G. J. Wilson. Biomechanical and ultrastructural comparison of cryopreservation and a novel cellular extraction of porcine aortic valve leaflets. J. Biomed. Mater. Res. 29(12):1507–1516, 1995.

    Article  Google Scholar 

  8. da Costa, F. D., A. C. Costa, R. Prestes, A. C. Domanski, E. M. Balbi, A. D. Ferreira, et al. The early and midterm function of decellularized aortic valve allografts. Ann. Thorac. Surg. 90(6):1854–1860, 2010. doi:S0003-4975(10)01872-2[pii]10.1016/j.athoracsur.2010.08.022.

    Article  Google Scholar 

  9. Fung, Y. C. Biomechanics: Mechanical Properties of Living Tissues. New York: Springer, 1981.

    Google Scholar 

  10. Gloeckner, D. C., K. L. Billiar, and M. S. Sacks. Effects of mechanical fatigue on the bending properties of the porcine bioprosthetic heart valve. ASAIO J. 45(1):59–63, 1999.

    Article  Google Scholar 

  11. Grabow, N., K. Schmohl, A. Khosravi, M. Philipp, M. Scharfschwerdt, B. Graf, et al. Mechanical and structural properties of a novel hybrid heart valve scaffold for tissue engineering. Artif. Organs. 28(11):971–979, 2004.

    Article  Google Scholar 

  12. Hammermeister, K., G. K. Sethi, W. G. Henderson, F. L. Grover, C. Oprian, and S. H. Rahimtoola. 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, 2000.

    Article  Google Scholar 

  13. Hoerstrup, S. P., R. Sodian, S. Daebritz, J. Wang, E. A. Bacha, D. P. Martin, et al. Functional living trileaflet heart valves grown in vitro. Circulation 102(19 Suppl 3):III44–III49, 2000.

    Google Scholar 

  14. Joyce, E. M., J. Liao, F. J. Schoen, J. E. Mayer, Jr., and M. S. Sacks. Functional collagen fiber architecture of the pulmonary heart valve cusp. Ann. Thorac. Surg. 87(4):1240–1249, 2009. doi:S0003-4975(08)02694-5[pii]10.1016/j.athoracsur.2008.12.049..

    Article  Google Scholar 

  15. Korossis, S. A., C. Booth, H. E. Wilcox, K. G. Watterson, J. N. Kearney, J. Fisher, et al. Tissue engineering of cardiac valve prostheses II: biomechanical characterization of decellularized porcine aortic heart valves. J. Heart Valve Dis. 11(4):463–471, 2002.

    Google Scholar 

  16. Lee, T. C., R. J. Midura, V. C. Hascall, and I. Vesely. The effect of elastin damage on the mechanics of the aortic valve. J. Biomech. 34(2):203–210, 2001. doi:S0021-9290(00)00187-1[pii].

    Article  Google Scholar 

  17. Liao, J., E. M. Joyce, and M. S. Sacks. Effects of decellularization on mechanical and structural properties of the porcine aortic valve leaflets. Biomaterials 29(8):1065–1074, 2008.

    Article  Google Scholar 

  18. Liao, J., L. Yang, J. Grashow, and M. S. Sacks. Molecular orientation of collagen in intact planar connective tissues under biaxial stretch. Acta Biomater. 1(1):45–54, 2005.

    Article  Google Scholar 

  19. Liao, J., L. Yang, J. Grashow, and M. S. Sacks. The relation between collagen fibril kinematics and mechanical properties in the mitral valve anterior leaflet. J. Biomech. Eng. 129(1):78–87, 2007.

    Article  Google Scholar 

  20. Lovekamp, J. J., D. T. Simionescu, J. J. Mercuri, B. Zubiate, M. S. Sacks, and N. R. Vyavahare. Stability and function of glycosaminoglycans in porcine bioprosthetic heart valves. Biomaterials 27(8):1507–1518, 2006.

    Article  Google Scholar 

  21. Rabkin-Aikawa, E., M. Aikawa, M. Farber, J. R. Kratz, G. Garcia-Cardena, N. T. Kouchoukos, et al. Clinical pulmonary autograft valves: pathologic evidence of adaptive remodeling in the aortic site. J. Thorac. Cardiovasc. Surg. 128(4):552–561, 2004.

    Article  Google Scholar 

  22. Rajani, B., R. B. Mee, and N. B. Ratliff. Evidence for rejection of homograft cardiac valves in infants. J. Thorac. Cardiovasc. Surg. 115(1):111–117, 1998.

    Article  Google Scholar 

  23. Sacks, M. S., F. J. Schoen, and J. E. Mayer. Bioengineering challenges for heart valve tissue engineering. Annu. Rev. Biomed. Eng. 11:289–313, 2009. doi:10.1146/annurev-bioeng-061008-124903.

    Article  Google Scholar 

  24. Sacks, M. S., D. B. Smith, and E. D. Hiester. A small angle light scattering device for planar connective tissue microstructural analysis. Ann. Biomed. Eng. 25(4):678–689, 1997.

    Article  Google Scholar 

  25. Schoen, F. J. Pathology of heart valve substitution with mechanical and tissue prostheses. In: Cardiovascular Pathology, edited by M. D. Silver, A. I. Gotlieb, and F. J. Schoen. New York: Livingstone, 2001.

    Google Scholar 

  26. Schoen, F. J. Heart valve tissue engineering: quo vadis? Curr. Opin. Biotechnol. 2011. doi:S0958-1669(11)00018-8[pii]10.1016/j.copbio.2011.01.004.

    Google Scholar 

  27. Schoen, F., and R. Levy. Tissue heart valves: current challenges and future research perspectives. J. Biomed. Mater. Res. 47:439–465, 1999.

    Article  Google Scholar 

  28. Schoen, F., R. Levy, and H. Piehler. Pathological considerations in replacement cardiac valves. Cardiovasc. Pathol. 1(1):29–52, 1992.

    Article  Google Scholar 

  29. Senthilnathan, V., T. Treasure, G. Grunkemeier, and A. Starr. Heart valves: which is the best choice? Cardiovasc. Surg. 7(4):393–397, 1999.

    Article  Google Scholar 

  30. Shinoka, T., C. K. Breuer, R. E. Tanel, G. Zund, T. Miura, P. X. Ma, et al. Tissue engineering heart valves: valve leaflet replacement study in a lamb model. Ann. Thorac. Surg. 60(6 Suppl):S513–S516, 1995.

    Article  Google Scholar 

  31. Sodian, R., S. P. Hoerstrup, J. S. Sperling, S. Daebritz, D. P. Martin, A. M. Moran, 19 Suppl 3, et al. Early In vivo experience with tissue-engineered trileaflet heart valves. Circulation 102(19 Suppl 3):III22–III29, 2000.

    Google Scholar 

  32. Spina, M., F. Ortolani, A. E. Messlemani, A. Gandaglia, J. Bujan, N. Garcia-Honduvilla, et al. Isolation of intact aortic valve scaffolds for heart-valve bioprostheses: extracellular matrix structure, prevention from calcification, and cell repopulation features. J. Biomed. Mater. Res. A. 67(4):1338–1350, 2003.

    Article  Google Scholar 

  33. Stamm, C., A. Khosravi, N. Grabow, K. Schmohl, N. Treckmann, A. Drechsel, et al. Biomatrix/polymer composite material for heart valve tissue engineering. Ann. Thorac. Surg. 78(6):2084–2093, 2004.

    Article  Google Scholar 

  34. Steinhoff, G., U. Stock, N. Karim, H. Mertsching, A. Timke, R. R. Meliss, et al. Tissue engineering of pulmonary heart valves on allogenic acellular matrix conduits: in vivo restoration of valve tissue. Circulation 102(19 Suppl 3):III50–III55, 2000.

    Google Scholar 

  35. Stock, U. A., M. Nagashima, P. N. Khalil, G. D. Nollert, T. Herden, J. S. Sperling, et al. Tissue-engineered valved conduits in the pulmonary circulation. J. Thorac. Cardiovasc. Surg. 119(4 Pt 1):732–740, 2000.

    Article  Google Scholar 

  36. Stock, U. A., J. P. Vacanti, J. E. Mayer, Jr., and T. Wahlers. Tissue engineering of heart valves—current aspects. Thorac. Cardiovasc. Surg. 50(3):184–193, 2002.

    Article  Google Scholar 

  37. Thubrikar, M. The Aortic Valve. Boca Raton: CRC, 1990.

    Google Scholar 

  38. Vesely, I. Heart valve tissue engineering. Circ. Res. 97:743–755, 2005.

    Article  Google Scholar 

  39. Wilson, G. J., D. W. Courtman, P. Klement, J. M. Lee, and H. Yeger. Acellular matrix: a biomaterials approach for coronary artery bypass and heart valve replacement. Ann. Thorac. Surg. 60(2 Suppl):S353–S358, 1995.

    Article  Google Scholar 

  40. Wilson, G. J., H. Yeger, P. Klement, J. M. Lee, and D. W. Courtman. Acellular matrix allograft small caliber vascular prostheses. ASAIO Trans. 36(3):M340–M343, 1990.

    Google Scholar 

  41. Yacoub, M., N. R. Rasmi, T. M. Sundt, O. Lund, E. Boyland, R. Radley-Smith, et al. Fourteen-year experience with homovital homografts for aortic valve replacement. J. Thorac. Cardiovasc. Surg. 110(1):186–193, 1995; (discussion 93-4).

    Article  Google Scholar 

  42. Yacoub, M. H., and J. J. Takkenberg. Will heart valve tissue engineering change the world? Nat. Clin. Pract. Cardiovasc. Med. 2(2):60–61, 2005. doi:ncpcardio0112[pii]10.1038/ncpcardio0112.

    Article  Google Scholar 

  43. Yannas, I. Natural Materials. Biomaterial Science. San Diego: Academic Press, 1996.

    Google Scholar 

  44. 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(1):9–22, 2001.

    Article  Google Scholar 

Download references

Acknowledgment

This work is supported by American Heart Association (BGIA-0565346U) and Health Resources and Services Administration (DHHS R1CRH10429-01-00). JL is supported in part by NIH NL097321. The authors would like to thank Dr. Steve Elder for help and invaluable discussion.

Conflict of interet

All authors declare that there are no proprietary, financial, professional or other personal conflicts of interest that could inappropriately influence (bias) the work presented in this manuscript.

Author information

Authors and Affiliations

  1. Tissue Bioengineering Laboratory, Department of Agricultural and Biological Engineering, Computational Manufacturing and Design, CAVS, Mississippi State University, 130 Creelman Street, Mississippi State, MS, 39762, USA

    Jun Liao, Hugh L. Jones, Mina Tahai, M. F. Horstemeyer & Lakiesha N. Williams

  2. Department of Bioengineering and McGowan Institute for Regenerative Medicine, Cardiovascular Biomechanics Laboratory, University of Pittsburgh, Pittsburgh, PA, 15219, USA

    Erinn M. Joyce & Michael S. Sacks

  3. Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, 37235, USA

    W. David Merryman

  4. Department of Cardiac Surgery, Childrens’s Mercy Hospital and Clinics, Kansas City, MO, 64108, USA

    Richard A. Hopkins

Authors
  1. Jun Liao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Erinn M. Joyce
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. W. David Merryman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hugh L. Jones
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mina Tahai
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. F. Horstemeyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lakiesha N. Williams
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Richard A. Hopkins
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Michael S. Sacks
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jun Liao.

Additional information

Associate Editor Ajit P. Yoganathan oversaw the review of this article.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liao, J., Joyce, E.M., David Merryman, W. et al. The Intrinsic Fatigue Mechanism of the Porcine Aortic Valve Extracellular Matrix. Cardiovasc Eng Tech 3, 62–72 (2012). https://doi.org/10.1007/s13239-011-0080-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13239-011-0080-4

Keywords

Search

Navigation