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Formation of carbonated apatite particles from a supersaturated inorganic blood serum model

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Abstract

Pathological calcification is common among for instance dialysis patients, and this causes an increase in mortality risk. An elevated serum phosphate concentration among those patients strongly correlates to this increase. In this work investigations of the conditions, composition, crystallinity and morphology of in vitro calcification are performed and related to results from in vivo studies. The study was performed under conditions mimicking physiological ones, i.e. a pH around 7.40, a temperature of 37°C, an ionic strength of 150 mM and ion concentrations close to those in human serum including the effects of elevated phosphate concentrations. The course of precipitation involves an initial precipitate that subsequently re-dissolves to give another precipitate, in accordance with the well-known Ostwald ripening theory. The final bulk precipitate consists of a macroscopically amorphous carbonated apatite. The amorphous apatite is formed from assemblies of spherical particles in the μm range, in turn composed of nano-crystalline needles of about 10 × 100 nm. Even the initially formed precipitate, as well as a small amount of precipitate that occurs on the liquid surface, consist of a carbonated calcium phosphate. The in vitro observed carbonated apatite bears strong resemblance to in vivo cardiovascular calcification known from literature.

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Acknowledgements

Hans Hallstadius, former employee at Gambro′s Development Department, is acknowledged for constructing the particle sensor and Andreas Fischer at the Department of Chemistry, Royal Institute of Technology, Stockholm, Sweden, for performing the TGA and X-ray diffraction investigations. This project was supported by a grant from the Swedish Research Council (VR 621-2001-3653).

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Authors and Affiliations

  1. Gambro Corporate Research, Lund, Sweden

    Karin Sandin & Lars-Fride Olsson

  2. Department of Chemistry, Royal Institute of Technology, Stockholm, Sweden

    Karin Sandin & Lars Kloo

  3. nCHREM (National Center of High Resolution Electron Microscopy), Lund University, Lund, Sweden

    Pernilla Nevsten & Reine L. Wallenberg

Authors
  1. Karin Sandin
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  2. Lars Kloo
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  3. Pernilla Nevsten
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  4. Reine L. Wallenberg
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  5. Lars-Fride Olsson
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Corresponding author

Correspondence to Lars Kloo.

Appendix

Appendix

Concentrations were calculated by an in-house program system utilizing known equilibrium constants [33] for the conditions used. These data include complex formation, acid-base equilibrium, and solubility. When necessary, the values were corrected to apply to an ionic strength of 150 mM. The formation of complexes between calcium, phosphate and bicarbonate ions were taken into consideration. H2PO4 − (20%) and HPO4 2− (80%) are the dominating forms of orthophosphoric acid at pH 7.4. The other components, H3PO4 and PO4 3− were neglected. In the carbonate system, HCO3 − dominates (~95%); the other components are dissolved carbon dioxide (“carbonic acid”) CO2(aq) and the carbonate ion, CO3 2−. Since the concentration of the latter is <0.2 mM, the formation of the complex CaCO3(aq) was neglected. The acid constant pKa2 = 6.7 for the acid-base pair H2PO4 −/HPO4 2−. For the hydrogen carbonate system, the values have been obtained by interpolating between ionic strength 0.1 and 0.2 mM resulting in pKa1 = 6.07 for CO2(aq)/HCO3 − and pKa2 = 9.75 for HCO3 −/CO3 2−. The dissociation constant of water employed was pKw = 13.4. Only the complexes CaHPO4(aq) and CaHCO3 + with complex formation constants, logK, 1.9 and 1.1, respectively, were included.

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Sandin, K., Kloo, L., Nevsten, P. et al. Formation of carbonated apatite particles from a supersaturated inorganic blood serum model. J Mater Sci: Mater Med 20, 1677–1687 (2009). https://doi.org/10.1007/s10856-009-3735-z

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  • DOI: https://doi.org/10.1007/s10856-009-3735-z

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