Skip to main content
SpringerLink
Log in

In Vitro Calcification of Bioprosthetic Heart Valves: Investigation of Test Fluids

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

Abstract

Calcification is a major reason for the failure of bioprosthetic heart valves. Therefore, several attempts towards an accelerated in vitro model were undertaken in order to provide a cost- and time-saving method for the analysis of calcification processes. Due to the problem of superficial or spontaneous precipitation, which occurred in the fluids applied, we focused our study on the development of a near-physiological calcification fluid. The desired fluid should not precipitate spontaneously and should neither promote nor inhibit calcification. Eleven different fluid compositions were tested without contact to potentially calcifying materials. Crucial factors regarding the fluid properties were the ionic product, the ionic strength, and the degree of supersaturation concerning dicalciumphosphate-dihydrate, octacalciumphosphate, and hydroxyapatite. The fluids were kept in polyethylene bottles and exposed to a slight vibration within a durability tester at 37 °C. The precipitation propensity was monitored optically and colorimetrically. A structural analysis of the deposits was carried out by x-ray powder diffraction and IR-spectroscopy, which showed the development of the crystal phases that are relevant in vivo. Only two of the fluids did not precipitate. Resulting from the computations of the effective fluid contents, the saturation degree concerning dicalciumphosphate-dihydrate seems to be the key factor for spontaneous precipitation.

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

Similar content being viewed by others

Abbreviations

au:

Arbitrary unit

CaT :

Total calcium

Ca-Gluc:

Calcium gluconate

DCPD:

Dicalciumphosphate-dihydrate

fz :

Activity coefficient of z-valent ionic species

FTIR:

Fourier transform infrared spectroscopy

HAP:

Hydroxyapatite

I:

Ionic strength

IP:

Thermodynamic ionic product

IR:

Infrared

Ksp :

Thermodynamic solubility constant

OCP:

Octacalcium phosphate

PE:

Polyethylene

PT :

Total phosphate

PU:

Polyurethane

SCaP :

Degree of supersaturation

SBF:

Simulated body fluid

T:

Temperature

XRD:

x-Ray powder diffraction

References

  1. Bangert, K. Herstellung und Charakterisierung von Calciumorthophosphaten für die Anwendung als Knochenersatzwerkstoffe. 2005

  2. Bernacca, G. M., A. C. Fisher, T. G. Mackay, and D. J. Wheatley. A dynamic in vitro method for studying bioprosthetic heart valve calcification. J. Mater. Sci. Mater. Med. 3:293–298, 1992.

    Article  CAS  Google Scholar 

  3. Chughtai, A., R. Marshall, and G. H. Nancollas. Complexes in calcium phosphate solutions. J. Phys. Chem. 72:208–211, 1968.

    Article  CAS  Google Scholar 

  4. Deiwick, M., B. Glasmacher, E. Pettenazzo, et al. Primary tissue failure of bioprostheses: new evidence from In vitro tests. Thorac. Cardiovasc. Surg. 49:78–83, 2001.

    Article  CAS  Google Scholar 

  5. Deiwick, M., B. Glasmacher, A. M. Zarubin, et al. Quality control of bioprosthetic heart valves by means of holographic interferometry. J. Heart Valve Dis. 5:441–447, 1996.

    CAS  PubMed  Google Scholar 

  6. Dorozhkin, S. V., and M. Epple. Biological and medical significance of calcium phosphates. Angew. Chemie Int. Ed. 41:3130–3146, 2002.

    Article  CAS  Google Scholar 

  7. Dzemali, O., F. Bakhtiari, U. Steinseifer, et al. Hemodynamic performance of fresh and calcified aortic valve prostheses in critical low stroke volume. J. Heart Valve Dis. 17:317–324, 2008.

    PubMed  Google Scholar 

  8. Dzemali, O., F. Bakhtiary, U. Steinseifer, et al. Hydrodynamic comparison of biological prostheses during progressive valve calcification in a simulated exercise situation. An in vitro study. Eur. J. Cardiothorac. Surg. 34:960–963, 2008.

    Article  Google Scholar 

  9. Eisenbrand, G., and P. Schreier (eds.). Römpp Lexikon Lebensmittelchemie. Stuttgart: Thieme Verlag, p. 447, 2006.

    Google Scholar 

  10. Epple, M. Biomaterialien und Biomineralisation. Eine Einführung für Naturwissenschaftler, Mediziner und Ingenieure. Wiesbaden: Teubner Verlag, p. 97, 2009.

    Google Scholar 

  11. Fowler, B. O., E. C. Moreno, and W. E. Brown. Infra-red spectra of hydroxyapatite, octacalcium phosphate and pyrolysed octacalcium phosphate. Arch. Oral Biol. 11:477–492, 1966.

    Article  CAS  Google Scholar 

  12. Glasmacher, B. Calcification of Polyurethan Biomaterials in the Cardiovascular System., 1991.

  13. Golomb, G., and D. Wagner. Development of a new in vitro model for studying implantable polyurethane calcification. Biomaterials 12:397–405, 1991.

    Article  CAS  Google Scholar 

  14. Gressner, A. M., and T. Arndt. Lexikon der medizinischen Laboratoriumsdiagnostik. Berlin: Springer-Verlag, p. 437, 2013.

    Book  Google Scholar 

  15. Hallbach, J. Klinische Chemie und Hämatologie für den Einstieg. Stuttgart: Thieme Verlag, p. 233, 2006.

    Google Scholar 

  16. Hesse, M., H. Meier, and B. Zeeh. Spektroskopische Methoden in der organischen Chemie. Stuttgart: Thieme Verlag, p. 44, 2016.

    Google Scholar 

  17. Heughebaert, J. C., and G. H. Nancollas. Kinetics of crystallization of octacalcium phosphate. J. Phys. Chem. 88:2478–2481, 1984.

    Article  CAS  Google Scholar 

  18. Kokubo, T., H. Kushitani, S. Sakka, T. Kitsugi, and T. Yamamuro. Solutions able to reproduce in vivo surface-structure changes in bioactive glass-ceramic A-W. J. Biomed. Mater. Res. 24:721–734, 1990.

    Article  CAS  Google Scholar 

  19. Koutsoukos, P., Z. Amjad, M. B. Tomson, and G. H. Nancollas. Crystallization of calcium phosphates. A constant composition study. J. Am. Chem. Soc. 102:1553–1557, 1980.

    Article  CAS  Google Scholar 

  20. Krings, M., D. Kanellopoulou, D. Mavrilas, and B. Glasmacher. In vitro pH-controlled calcification of biological heart valve prostheses. Mat.-Wiss. und Werkstofftech 37:432–435, 2006.

    Article  CAS  Google Scholar 

  21. LeGeros, R. Z. Preparation of octacalcium phosphate: a direct fast method. Calcif. Tissue Int. 37(194–197):20, 1985.

    Google Scholar 

  22. Löffler, G., and P. E. Petrides. Physiologische Chemie. Berlin: Springer-Verlag, p. 545, 2013.

    Google Scholar 

  23. Marshall, R. W., and G. H. Nancollas. The kinetics of crystal growth of dicalcium phosphate dihydrate. J. Phys. Chem. 73:3838–3844, 1969.

    Article  CAS  Google Scholar 

  24. Nancollas, G. H., M. Lore, L. Perez, C. Richardson, and S. J. Zawacki. Mineral phases of calcium phosphate. Anat. Record. 224:234–241, 1989.

    Article  CAS  Google Scholar 

  25. Nancollas, G. H., and B. Tomažič. Growth of calcium phosphate on hydroxyapatite crystals. Effect of supersaturation and ionic medium. J. Phys. Chem. 78:2218–2225, 1974.

    Article  CAS  Google Scholar 

  26. Neumeister, B., and B. O. Böhm. Klinikleitfaden Labordiagnostik. München: Elsevier, p. 219, 2018.

    Google Scholar 

  27. O’Neill, W. C. The fallacy of the calcium-phosphorus product. Kidney Int. 72:792–796, 2007.

    Article  Google Scholar 

  28. Pallagi, A. Interaction of Calcium with Sugar Type Ligands in Solutions related to the Bayer Process., 2011.

  29. Peters, F. Biologische Kristallisation von Calciumphosphaten – Untersuchung und Simulation., 2001.

  30. Prymak, O. Untersuchung zu Biomaterialien und Biomineralien auf der Basis von Nickel-Titan-Legierungen und Calciumphosphaten., 2005.

  31. Radke, J. Das ionisierte Calcium im Extrazellularraum bei Hyperthermie und Azidose. Berlin: Springer-Verlag, p. 37, 1988.

    Book  Google Scholar 

  32. Schoen, R. J., and F. J. Levy. Calcification of tissue heart valve substitutes: progress toward understanding and prevention. Ann. Thorac. Surg. 79:1072–1080, 2005.

    Article  Google Scholar 

  33. Starcher, C., and D. W. Urry. Elastin coacervate as a matrix for calcification. Biochem. Biophys. Res. Commun. 53:210–216, 1973.

    Article  CAS  Google Scholar 

  34. Tadic, D. Synthese und Charakterisierung von Knochenmineral-ähnlichen Calciumphosphaten. Herstellung eines synthetischen Biomaterials., 2003.

  35. Ter Braake, A. D., P. T. Tinnemans, C. M. Shanahan, J. G. J. Hoenderop, and J. H. F. de Baaij. Magnesium prevents vascular calcification in vitro by inhibiting of hydroxyapatite crystal formation. Sci. Rep., 2018.https://doi.org/10.1038/s41598-018-20241-3

    Article  PubMed  PubMed Central  Google Scholar 

  36. Vavrusova, M., M. B. Munk, and L. H. Skibsted. Aqueous solubility of calcium L-lactate, calcium D-Gluconate, and calcium D-lactobionate: Importance of complex formation for solubility increase by hydroxycarboxylate mixtures. J. Agric. Food Chem. 61:8207–8214, 2013.

    Article  CAS  Google Scholar 

  37. Zilla, P., C. Weissenstein, P. Human, T. Dower, and U. O. von Oppel. High glutaraldehyde concentrations mitigate bioprosthetic root calcification in the sheep model. Ann. Thorac. Surg. 70:2091–2095, 2000.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We thank the Institute of Laboratory Animal Science, Uniklinik RWTH Aachen for the chemical analysis of the fluid compositions, and Irmgard Kalf (Institute of Inorganic Chemistry, RWTH Aachen University) for the FTIR measurements.

Funding

Parts of this study were funded by INTERREG Program V-A Euregio Maas-Rhine of the European Union (Grant No. 2016/98602) and by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—403041552.

Author information

Authors and Affiliations

  1. Department of Cardiovascular Engineering, Institute of Applied Medical Engineering, Helmholtz Institute Aachen, RWTH Aachen University, Aachen, Germany

    N. Kiesendahl, C. Schmitz, M. Menne, J. Arens & U. Steinseifer

  2. Institute of Applied Medical Engineering, Helmholtz Institute Aachen, RWTH Aachen University, Pauwelsstraße 20, 52074, Aachen, Germany

    T. Schmitz-Rode & U. Steinseifer

  3. Monash Institute of Medical Engineering and Department of Mechanical and Aerospace Engineering, Monash University, Melbourne, Australia

    U. Steinseifer

  4. Institute of Crystallography, RWTH Aachen University, Aachen, Germany

    A. Von Berg

Authors
  1. N. Kiesendahl
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Schmitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Von Berg
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Menne
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. T. Schmitz-Rode
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J. Arens
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. U. Steinseifer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to U. Steinseifer.

Additional information

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

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 70 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kiesendahl, N., Schmitz, C., Von Berg, A. et al. In Vitro Calcification of Bioprosthetic Heart Valves: Investigation of Test Fluids. Ann Biomed Eng 48, 282–297 (2020). https://doi.org/10.1007/s10439-019-02347-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-019-02347-5

Keywords

Search

Navigation