Enhanced osteoconductivity of sodium‐substituted hydroxyapatite by system instability

Abstract The effect of substituting sodium for calcium on enhanced osteoconductivity of hydroxyapatite was newly investigated. Sodium‐substituted hydroxyapatite was synthesized by reacting calcium hydroxide and phosphoric acid with sodium nitrate followed by sintering. As a control, pure hydroxyapatite was prepared under identical conditions, but without the addition of sodium nitrate. Substitution of calcium with sodium in hydroxyapatite produced the structural vacancies for carbonate ion from phosphate site and hydrogen ion from hydroxide site of hydroxyapatite after sintering. The total system energy of sodium‐substituted hydroxyapatite with structural defects calculated by ab initio methods based on quantum mechanics was much higher than that of hydroxyapatite, suggesting that the sodium‐substituted hydroxyapatite was energetically less stable compared with hydroxyapatite. Indeed, sodium‐substituted hydroxyapatite exhibited higher dissolution behavior of constituent elements of hydroxyapatite in simulated body fluid (SBF) and Tris‐buffered deionized water compared with hydroxyapatite, which directly affected low‐crystalline hydroxyl‐carbonate apatite forming capacity by increasing the degree of apatite supersaturation in SBF. Actually, sodium‐substituted hydroxyapatite exhibited markedly improved low‐crystalline hydroxyl‐carbonate apatite forming capacity in SBF and noticeably higher osteoconductivity 4 weeks after implantation in calvarial defects of New Zealand white rabbits compared with hydroxyapatite. In addition, there were no statistically significant differences between hydroxyapatite and sodium‐substituted hydroxyapatite on cytotoxicity as determined by BCA assay. Taken together, these results indicate that sodium‐substituted hydroxyapatite with structural defects has promising potential for use as a bone grafting material due to its enhanced osteoconductivity compared with hydroxyapatite. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 1046–1062, 2014.