Injectable magnesium-doped brushite cement for controlled drug release application

Abstract

Dicalcium phosphate dihydrate (CaHPO4·2H2O), also known as brushite, is one of the important bioceramics for bone regeneration. However, fast setting of the brushite cement under physiological conditions has limited its clinical use. Furthermore, brushite cement without any additives normally has poor injectability due to the liquid–solid phase separation. In the present study, magnesium-doped β-tricalcium phosphate (Mg-β-TCP) with chemical formula of β-Ca2.96−xMgx(PO4)2 was used to prepare injectable brushite cements with improved physicochemical properties. β-TCP containing different amounts of Mg2+ ions were reacted with monocalcium phosphate monohydrate [Ca(H2PO4)2·H2O, MCPM] in the presence of water to furnish corresponding brushite cement. The samples were characterized using X-ray diffractometry, Fourier transform infrared spectroscopy and field emission scanning electron microscopy. The effect of magnesium ions on the structural, mechanical, and setting properties of the cements is reported. Our results indicate that the presence of Mg2+ ions increases the degree of injectability, setting time, and mechanical properties of the brushite cement. The compressive strength of brushite cement was substantially increased upon incorporation of Mg2+ ions. Furthermore, the setting times of the brushite cement were significantly improved. Gentamicin sulfate, amoxicillin and ampicillin trihydrate were incorporated into the Mg-brushite cement, and their release profiles showed a sustained drug release over 14 days. Cumulative releases of 99.3, 87, and 79 % were observed for gentamicin sulfate, amoxicillin, and ampicillin trihydrate, respectively.