Preparation, characterization, release kinetics, and in vitro cytotoxicity of calcium silicate cement as a risedronate delivery system

Abstract

Injectable bone cements have been well characterized and studied in non-load bearing bone fixation and bone screw augmentation applications. Current calcium phosphate cement or poly(methyl methacrylate) cement have drawbacks like low mechanical strength and in situ exothermic properties. This leads especially in patients with osteoporosis to worsening contact between implant and bone and can finally lead to implant failure. To improve these properties, a calcium silicate cement (CSC) was prepared, which additionally contained the bisphosphonate risedronate (RA) to promote osteoblast function. Cement setting rate and compressive strength were measured and found to be reduced by RA above 0.5 wt%. X-ray diffraction, Rietveld refinement analysis, scanning electron microscopy, and porosity measurements by gas sorption revealed that RA reduces calcium silicate hydrate gel formation and changes the cement's microstructure. Cumulative release profiles of RA from CSC up to 6 months into phosphate buffer solution were analyzed by high-performance liquid chromatography, and the results were compared with theoretical release curves obtained from the Higuchi equation. Fourier transform infrared spectra measurements and drug release studies indicate that calcium-RA formed within the cement, from which the drug can be slowly released over time. An investigation of the cytotoxicity of the RA-CSC systems upon osteoblast-like cells showed no toxic effects of concentrations up to 2%. The delivery of RA from within a CSC might thus be a valuable and biocompatible new approach to locally deliver RA and to reconstruct and/or repair osteoporosis-related bone fractures.

Keywords: biocompatibility; calcium silicate cement; cytotoxicity; drug delivery; risedronate.