Osteogenic lithium-doped brushite cements for bone regeneration.

Abstract

This study investigated the osteogenic performance of new brushite cements obtained from Li⁺-doped β-tricalcium phosphate as a promising strategy for bone regeneration. Lithium (Li⁺) is a promising trace element to encourage the migration and proliferation of adipose-derived stem cells (hASCs) and the osteogenic differentiation-related gene expression, essential for osteogenesis. <i>In-situ</i> X-ray diffraction (XRD) and <i>in-situ</i> ¹H nuclear magnetic resonance (¹H NMR) measurements proved the precipitation of brushite, as main phase, and monetite, indicating that Li⁺ favored the formation of monetite under certain conditions. Li⁺ was detected in the remaining pore solution in significant amounts after the completion of hydration. Isothermal calorimetry results showed an accelerating effect of Li⁺, especially for low concentration of the setting retarder (phytic acid). A decrease of initial and final setting times with increasing amount of Li⁺ was detected and setting times could be well adjusted by varying the setting retarder concentration. The cements presented compressive mechanical strength within the ranges reported for cancellous bone. <i>In vitro</i> assays using hASCs showed normal metabolic and proliferative levels. The immunodetection and gene expression profile of osteogenic-related markers highlight the incorporation of Li⁺ for increasing the <i>in vivo</i> bone density. The osteogenic potential of Li-doped brushite cements may be recommended for further research on bone defect repair strategies.