On the importance of surface and interface contaminants in β-tricalcium phosphate bone graft substitutes

Doping calcium phosphates (CaPs) has been very popular since the publication of Gibson et al (1999) reporting the synthesis of Si-substituted hydroxyapatite [1]. Generally, the main aim of this approach is to modify CaPs biological response by adding a biological relevant anion or cation in the CaP crystal structure. In other words, CaPs are used as carrier for inorganic drugs, and the release of these inorganic drugs occur during CaP resorption. Unfortunately, the incorporation of foreign ions in the CaP crystal structure modifies the crystal shape and solubility, and as such, it is not possible to univocally attribute a biological effect to the release of the incorporated inorganic drug. Indeed, it could also be due to a change of surface topography or a change Ca or phosphate release [2]. Another difficulty related to CaP doping is associated with the determination of the location of the doping agents. Most studies conclude from a change of crystal lattice parameters that all inorganic drugs are incorporated in the crystal lattice even though part of the ions could be located at grain boundaries [2-3]. The aim of this communication is threefold: (i) briefly summarize this field of research, (ii) describe and illustrate the difficulties to produce pure calcium phosphate powders and sintered blocks, and finally (iii) present some in vitro data demonstrating the link between processing conditions (incl. sintering), purity / doping, and osteoclastic resorption. It will be in particular shown that the sintering atmosphere, surface impurities due to phosphate evaporation during sintering, and the Ca/P molar ratio affects the osteoclastic response. Data on Sr and Cu-doping will also be presented.

REFERENCES: 1 I.R. Gibson, S.M. Best, W. Bonfield (1999) J Biomed Mater Res 44:422-428. 2 M. Bohner (2009) Biomaterials 30:6403-6406. 3 G. Gasqueres, C. Bonhomme, J. Maquet et al (2008) Magn Res Chem 46:342-346.