Octacalcium Phosphate Doped with Barium Cations for Application in Tissue Engineering

The effect of barium cation doping of octacalcium phosphate powder obtained using a low-temperature method on its phase and structural characteristics, as well as biocompatibility, including under in vitro conditions simulating inflammation, has been studied. It was found that doping with Ba2+ cations in the concentration range used (1, 5, and 10 calculated%) does not interfere with the low-temperature chemical transformation of dicalcium phosphate dihydrate and its conversion to octacalcium phosphate; however, the actual substitution is at a maximum of 6.7 at %. The results of in vitro studies show that the replacement of calcium ions with barium ions in the structure of octacalcium phosphate does not lead to an increase in cytotoxic properties; all studied variants of low-temperature octacalcium phosphate and its barium-substituted forms at the recommended concentration of 1 mg/mL do not exhibit toxic effects and are biocompatible. The effects identified for octacalcium phosphate with a maximum degree of Ca2+ substitution by Ba2+ equal to 10%, namely the absence of an effect on the content of lysosomes and reactive oxygen species in human macrophages under normal conditions and a significant decrease in the production of reactive oxygen species under conditions simulating inflammation, as well as a significant increase in the constitutive activation of T-lymphocytes in vitro, indicate that these processes are directly and dose-dependently associated with Ba2+ cations in the composition of octacalcium phosphate. Thus, the proposed method of low-temperature chemical transformation of Ba2+-substituted variants of octacalcium phosphate is promising and is of interest for obtaining materials based on calcium phosphate compounds with immunoregulatory properties. The obtained Ba2+-substituted variants of octacalcium phosphate are safe and biocompatible, while octacalcium phosphate with the maximum degree of Ca2+ substitution by Ba2+ is not only bioactive, but also has potential antioxidant and immunomodulatory effects.