Inhibition of apatite formation by titanium and vanadium ions

Abstract

Ti4+ and V5+ ions were studied in two biologically relevant in vitro test systems to determine their effect on hydroxyapatite (HA) formation. System 1 involved direct HA precipitation from solution, and system 2 dealt with the growth of HA seed crystals. The experiments were carried out in a pH-stat by continuously recording NaOH uptake, which follows HA formation kinetics, at pH 7.4, 37 degrees C, and 0.15 M NaCl. In systems 1 and 2, Ti decreased HA formation kinetics in a dose-related manner without delaying the onset of HA formation. For V, the rate of HA proliferation decreased in system 1 in a dose-related manner, but the curves displayed a complicated shape. In system 2, V brought about a decrease in the HA seeded growth rate. Previous work has shown that Al blocks HA proliferation by adsorbing to active growth sites on the surface of HA crystals. By contrast, in this study V was found not to be adsorbed to the surface of HA. The mechanism of action of V probably involves the poorly understood hydrolysis and solution complex formation chemistry of the metal ion. We have shown here that V ions form V-PO4 complexes in solution in the HA formation systems; undoubtedly these are involved in the mechanism of V inhibition of HA formation. On the other hand, Ti was shown to bind to the surface of HA crystals in this study, which means that the ion may poison active crystal growth sites, as does aluminum. Ti-6Al-4V alloy is widely used in cementless total hip implants. Previous studies have shown that Ti concentrations 10 to 100 times higher than used here accumulate in osseous tissues around porous Ti implants in dogs 6 to 12 months after implantation. Ions leaching out over long periods of time into the implant interface could interfere with the normal osteoid mineralization and remodeling processes of bone in that region, which would result in subsequent loosening of the implant. This research suggests that further in vitro and animal studies should be carried out to determine the extent of Ti and V ion leaching from implants and their effect on tissue mineralization.