Biomechanical properties of hybrid heart valve prosthesis utilizing the pigs that do not express the galactose-α-1,3-galactose (α-Gal) antigen derived tissue and tissue engineering technique

  • Piotr Wilczek
  • Anna Lesiak
  • Aleksandra Niemiec-Cyganek
  • Barbara Kubin
  • Ryszard Slomski
  • Jerzy Nozynski
  • Grazyna Wilczek
  • Aldona Mzyk
  • Michalina Gramatyka
Tissue Engineering Constructs and Cell Substrates
Part of the following topical collections:
  1. Clinical Applications of Biomaterials


The aim of the study was to estimate the biomechanical properties of heart valves conduit derived from transgenic pigs to determine the usefulness for the preparation of tissue-engineered heart valves. The acellular aortic and pulmonary valve conduits from transgenic pigs were used to estimate the biomechanical properties of the valve. Non-transgenic porcine heart valve conduits were used as a reference. The biomechanics stability of acellular valve conduits decreased both for the transgenic and non-transgenic porcine valves. The energy required to break the native pulmonary valve derived from transgenic pigs was higher (20,475 ± 7,600 J m−2) compared with native non-transgenic pigs (12,140 ± 5,370 J m−2). After acellularization, the energy to break the valves decreased to 14,600 and 8,800 J m−2 for the transgenic pulmonary valve and non-transgenic valve, respectively. The native transgenic pulmonary valve showed a higher extensibility (42.70 %) than the non-transgenic pulmonary valve (35.50 %); the extensibility decreased after acellularization to 41.1 and 31.5 % for the transgenic and non-transgenic valves, respectively. The pulmonary valves derived from transgenic pigs demonstrate better biomechanical properties compared with non-transgenic. Heart valves derived from transgenic pigs can be valuable for the preparation of tissue-engineered bioprostheses, because of their biomechanical properties, stability, reduced immune response, making them safer for clinical applications.


Heart Valve Biomechanical Property Pulmonary Valve Porcine Tissue Heart Valve Prosthesis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported by Grant Applied Research Programme of the National Centre for Research and Development NR 13 0075 06.

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  1. 1.
    Rahimtoola SH. Review choice of prosthetic heart valve for adult patients. J Am Coll Cardiol. 2011;41:893–904.CrossRefGoogle Scholar
  2. 2.
    Hammermeister K, Sethi GK, Henderson WG, Grover FL, Oprian C, Rahimtoola SH. 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. 2000;36:1152–8.CrossRefGoogle Scholar
  3. 3.
    Schoen FJ. Pathology of heart valve substitution with mechanical and tissue prostheses. In: Silver MD, Gotlieb AI, Schoen FJ, editors. Cardiovascular pathology. New York: Churchill Livingstone; 2001. p. 629–77.Google Scholar
  4. 4.
    Jamieson WR, von Lipinski O, Miyagishima RT, Burr LH, Janusz MT, Ling H, Fradet GJ, Chan F, Germann E. Performance of bioprostheses and mechanical prostheses assessed by composites of valve-related complications to 15 years after mitral valve replacement. J Thorac Cardiovasc Surg. 2005;129:1301–8.CrossRefGoogle Scholar
  5. 5.
    Burdon TA, Miller DC, Oyer PE, Mitchell RS, Stinson EB, Starnes VA, Shumway NE. Durability of porcine valves at fifteen years in a representative North American patient population. J Thorac Cardiovasc Surg. 1992;103:238–51.Google Scholar
  6. 6.
    Vongpatanasin W, Hillis LD, Lange RA. Review prosthetic heart valves. N Engl J Med. 1996;335:407–16.CrossRefGoogle Scholar
  7. 7.
    Cascalho M, Platt JL. The immunological barrier to xenotransplantation. Immunity. 2001;14:437–46.CrossRefGoogle Scholar
  8. 8.
    Cooper DK, Koren E, Oriol R. Oligosaccharides and discordant xenotransplantation. Immunol Rev. 1994;141:31–58.CrossRefGoogle Scholar
  9. 9.
    Galili U. Interaction of the natural anti-Gal antibody with α-galactosyl epitopes: a major obstacle for xenotransplantation in humans. Immunol Today. 1993;14:480–2.CrossRefGoogle Scholar
  10. 10.
    Sandrin MS, McKenzie IF. Galα (1,3) Gal, the major xenoantigen(s) recognized in pigs by human natural antibodies. Immunol Rev. 1994;141:169–90.CrossRefGoogle Scholar
  11. 11.
    Golomb G, Schoen FJ, Smith MS, Linden J, Dixon M, Levy RJ. The role of glutaraldehyde-induced cross-links in calcification of bovine pericardium used in cardiac valve bioprostheses. Am J Pathol. 1987;127:122–30.Google Scholar
  12. 12.
    Milano A, Bortolotti U, Talenti E, Valfre C, Arbustini E, Valente M. Calcific degeneration as the main cause of porcine bioprosthetic valve dysfunction. Am J Cardiol. 1984;53:1066–70.CrossRefGoogle Scholar
  13. 13.
    Schoen FJ, Levy RJ. Bioprosthetic heart valve failure: pathology and pathogenesis. Cardiol Clin. 1984;2:717–39.Google Scholar
  14. 14.
    Wilczek P. Heart valve bioprothesis; effect of different acellularizations methods on the biomechanical and morphological properties of porcine aortic and pulmonary valve. Bull Pol Acad Sci. 2010;58:337–42.Google Scholar
  15. 15.
    Baumann BC, Forte P, Hawley RJ, Rieben R, Schneider MKJ, Seebach JD. Lack of galactose-α-1,3-galactose expression on porcine endothelial cells prevents complement-induced lysis but not direct xenogeneic NK cytotoxicity. J Immunol. 2004;172:6460C–6467.CrossRefGoogle Scholar
  16. 16.
    Lam TT, Hausen B, Boeke-Purkis K, Paniagua R, Lau M, Hook L, Berry G, Higgins J, Duthaler RO, Katopodis AG, Robbins R, Reitz B, Borie D, Schuurman H-J, Morris RE. Hyperacute rejection of hDAF-transgenic pig organ xenografts in cynomolgus monkeys: influence of pre-existing anti-pig antibodies and prevention by the alpha GAL glycoconjugate GAS914. Xenotransplantation. 2004;11:517–24.CrossRefGoogle Scholar
  17. 17.
    Hoerstrup SP, Sodian R, Daebritz S, Wang J, Bacha EA, Martin DP, Moran AM, Guleserian KJ, Sperling JS, Kaushal S, Vacanti JP, Schoen FJ, Mayer JE Jr. Functional living trileaflet heart valves grown in vitro. Circulation. 2000;102:44–9.CrossRefGoogle Scholar
  18. 18.
    Mendelson K, Schoen FJ. Heart valve tissue engineering: concepts, approaches, progress and challenges. Ann Biomed Eng. 2006;34:1799–819.CrossRefGoogle Scholar
  19. 19.
    Rieder E, Seebacher G, Kasimir MT, Eichmair E, Winter B, Dekan B, Wolner E, Simon P, Weigel G. Tissue engineering of heart valves: decellularized porcine and human valve scaffolds differ importantly in residual potential to attract monocytic cells. Circulation. 2005;111:2792–7.CrossRefGoogle Scholar
  20. 20.
    Gonçalves AC, Griffiths LG, Anthony RV, Orton EC. Decellularization of bovine pericardium for tissue-engineering by targeted removal of xenoantigens. J Heart Valve Dis. 2005;14:212–7.Google Scholar
  21. 21.
    Rieder E, Kasimir M-T, Silberhumer G, Seebacher G, Wolner E, Simon P, Weigel G. 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. 2004;127:399–405.CrossRefGoogle Scholar
  22. 22.
    Kasimir M-T, Rieder E, Seebacher G, Nigisch A, Dekan B, Wolner E, Weigel G, Simon P. Decellularization does not eliminate thrombogenicity and inflammatory stimulation in tissue-engineered porcine heart valves. J Heart Valve Dis. 2006;15:278–86.Google Scholar
  23. 23.
    Simon P, Kasimir MT, Seebacher G, Weigel G, Ullrich R, Salzer-Muhar U, Rieder E, Wolner E. Early failure of the tissue engineered porcine heart valve SYNERGRAFT in pediatric patients. Eur J Cardiothorac Surg. 2003;23:1002–6.CrossRefGoogle Scholar
  24. 24.
    Bader A, Steinhoff G, Strobl K, Schilling T, Brandes G, Mertsching H, Tsikas D, Froelich J, Haverich A. Engineering of human vascular tissue based on a xenogeneic starter matrix. Transplantation. 2000;70:7–14.Google Scholar
  25. 25.
    Livi U, Abdulla A-K, Parker R, Olsen EJ, Ross DN. Viability andmorphology of aortic and pulmonary homographs. J Thorac Cardiovasc Surg. 1987;93:755–60.Google Scholar
  26. 26.
    Gerosa G, Ross DN, Bruecke P, Dziatkowiak A, Mohammed S, Norman D, Davies J, Sbarbati A, Casarotto D. Aortic valve replacement with pulmonary homografts early experience. J Thorac Cardiovasc Surg. 1994;107:424–37.Google Scholar
  27. 27.
    Liao J, Erinn EM, Sacks MS. Effects of decellularization on the mechanical and structural properties of the porcine aortic valve leaflet. Biomaterials. 2008;29:1065–74.CrossRefGoogle Scholar
  28. 28.
    Li W, Liu W-Y, Yi D-H, Yu S-Q, Jin Z-H. Histological/biological characterization of decellularized bovine jugular vein. Asian Cardiovasc Thorac Ann. 2007;15:91–6.CrossRefGoogle Scholar
  29. 29.
    Grauss RW, Hazekamp MG, Oppenhuizen F, van Munsteren CJ, Gittenberger-de Groot AC, DeRuiter MC. Histological evaluation of decellularised porcine aortic valves: matrix changes due to different decellularisation methods. Eur J Cardiothorac Surg. 2005;27:566–71.CrossRefGoogle Scholar
  30. 30.
    Lee TC, Midura RJ, Hascall VC, Vesely I. The effect of elastin damage on the mechanics of the aortic valve. J Biomech. 2001;34:203–10.CrossRefGoogle Scholar
  31. 31.
    Talman EA, Boughner DR. Glutaraldehydefifixatio alters the internal shear properties of porcine aortic heart valve tissue. Ann Thorac Surg. 1995;60:S369–73.CrossRefGoogle Scholar
  32. 32.
    Fitzpatrick JC, Clark PM, Capaldi FM. Effect of decellularization protocol on the mechanical behavior of porcine descending aorta. Int J Biomater. 2010. doi: 10.1155/2010/620503.
  33. 33.
    Stamm C, Khosravi A, Grabow N, Schmohl K, Treckmann N, Drechsel A, Nan M, Schmitz KP, Axel H, Steinhoff G. Biomatrix/polymer composite material for heart valve tissue engineering. Ann Thorac Surg. 2004;78:2084–93.CrossRefGoogle Scholar
  34. 34.
    Leyh RG, Wilhelmi M, Rebe P, Fischer S, Kofidis T, Haverich A, Mertsching H. In vivo repopulation of xenogeneic and allogeneic acellular valve matrix conduits in the pulmonary circulation. Ann Thorac Surg. 2003;75:1457–63.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Piotr Wilczek
    • 1
  • Anna Lesiak
    • 1
  • Aleksandra Niemiec-Cyganek
    • 1
  • Barbara Kubin
    • 1
  • Ryszard Slomski
    • 2
  • Jerzy Nozynski
    • 3
  • Grazyna Wilczek
    • 4
  • Aldona Mzyk
    • 1
  • Michalina Gramatyka
    • 1
  1. 1.Bioengineering LaboratoryHeart Prosthesis InstituteZabrzePoland
  2. 2.Department of Biochemistry and BiotechnologyPoznan University of Life SciencesPoznanPoland
  3. 3.Department of Cardiac Surgery and TransplantologySilesian Centre for Heart DiseaseZabrzePoland
  4. 4.Department of Animal Physiology and Ecotoxicology, Faculty of Biology and Environmental ProtectionUniversity of SilesiaKatowicePoland

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