Immunomodulatory effect of OCP doped with strontium, magnesium, and barium cations in vitro

The development of modern osteoplastic materials with controlled immunomodulatory properties represents a critical objective in bone tissue engineering. Octacalcium phosphate (OCP) serves as a promising precursor to bone apatite; however, its clinical application is limited by inconsistent biological response for recipients with similar nosology. Ionic doping presents a prospective approach for enhancing the functional characteristics of calcium phosphates. This study is dedicated to the synthesis and in vitro investigation of the immunomodulatory effects of low-temperature OCP co-doped with Sr²⁺/Mg²⁺ and Sr²⁺/Ba²⁺. The developed materials were characterized using X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR). The incorporation of strontium during OCP synthesis was shown to destabilize the crystal lattice and reduce crystallite size. In vitro studies utilizing monocyte-like (THP-1 ATRA) and macrophage-like (THP-1 PMA) cell models demonstrated that the doped OCP materials did not induce cytotoxic effects and effectively modulated the functional activity of immune cells. Specifically, in monocyte-like cells, both OCP materials enhanced phagocytic activity and significantly increased the secretion of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). In macrophage-like cells, the materials reduced phagocytic activity and exerted dual ion-dependent effects on reactive oxygen species (ROS) production. Furthermore, they stimulated cytokine secretion predominantly under non-inflammatory conditions. Notably, OCP_Sr20_Mg1 induced a comparatively milder proinflammatory response compared to OCP_Sr20_Ba1, specifically reducing ROS formation and cytokine secretion by monocyte-like and macrophage-like cells under standard conditions. These results suggest that Sr/Mg co-doping may provide a more balanced immunomodulatory profile favorable for osteoplastic applications. The findings indicate that the immunomodulatory effect is likely mediated through direct particle-cell interactions influencing intracellular processes such as phagocytosis and lysosomal activity, rather than being solely attributable to soluble ion release.