Modulation of the human bone cell cycle by calcium ion-implantation of titanium

Ca ion implantation of Ti surfaces has previously been reported to enhances osseointegration in vivo. Although the mechanisms underlying the response of bone cells to these novel surfaces still remain unclear, it is possible that Ca ion-implanted Ti (Ca–Ti) may influence the growth of new bone by modulating the progression of the cell cycle. In the present study we have, therefore, examined the precise effects of Ca ion-implantation of Ti on the bone-like MG-63 cell line in vitro. The results of flow cytometry analysis showed that this surface markedly enhanced the proportion of cells which expressed Ki-67, a cell proliferation-associated nuclear antigen, compared with cells grown on the non-implanted Ti (control) surface. In addition, cultures grown on Ca–Ti and synchronized at the G1/S boundary by hydroxyurea more rapidly re-entered and progressed through the S and G2/M phases of the cell cycle than their counterparts on Ti. Ca ion-implantation also significantly increased the numbers of mitotic cells. These results thus show that alteration of the surface chemistry of Ti by high-energy implantation with Ca ion was able to substantially modulate the progression of the bone cell cycle, and suggest a possible means of enhancing the response of bone cells to implant materials.