Osteoblast response to hydroxyapatite doped with divalent and trivalent cations

The present in vitro study doped hydroxyapatite (HA) with various metal cations (Mg(2+), Zn(2+), La(3+), Y(3+), In(3+), and Bi(3+)) in an attempt to enhance properties of HA pertinent to orthopedic and dental applications. X-ray diffraction material characterization indicated that the metal cations may have substituted for calcium in the HA crystal structure and that all of the doped HA formulations were single-phase and crystalline. Scanning electron microscopy analysis revealed a variety of grain sizes, depending on the dopant utilized. Energy-dispersive spectroscopy confirmed that the dopants added during synthesis were present and that all of the HA formulations synthesized were within the defined range of HA phase in the CaO-P(2)O(5)-H(2)O system. Lastly, Bi-doped HA had a slower dissolution rate than either undoped HA or HA doped with other cations when exposed to simulated physiological conditions for 21 days. In terms of cell function, results provided the first evidence that osteoblasts, bone-forming cells, adhered and differentiated (as measured by alkaline phosphatase synthesis) in response to HA doped with trivalent cations (specifically, La(3+), Y(3+), In(3+), Bi(3+)) at earlier time points than either HA doped with divalent cations (Mg(2+), Zn(2+)) or undoped HA. Of the dopants examined, Bi(3+) most enhanced osteoblast long-term calcium-containing mineral deposition. For these reasons, this study revealed for the first time the potential benefits of doping HA with Bi(3+) according to criteria critical for bone prosthetic clinical success.