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.

A Comprehensive Study of Osteogenic Calcium Phosphate Silicate Cement: Material Characterization and In Vitro/In Vivo Testing

“…[ 16 ] The CPSC system tested in this work shows no cytotoxic effects on osteoblast cells and is found to be as in vitro biocompatible as the CSC system. [ 21 ] Cytotoxicity tests show that cell viabilities are higher in CPSC extracts than in the CSC extracts, although many of the results are not signifi cantly different. Additional fl ow cytometry and PCR experiments demonstrate that CPSC promotes osteoblast cell proliferation and prove that CPSC is in vitro biocompatible.…”

Postembedding Decalcification of Mineralized Tissue Sections Preserves the Integrity of Implanted Biomaterials and Minimizes Number of Experimental Animals

“…Moreover, recent developments focused on doping CPC to enhance healing. Bisphosphonates (i.e., risedronate) were utilized due to release kinetics properties and biocompatibility when tested on osteoblasts [4]. Zoledronate doped CPC showed increased bone density in μ CT and histology in ovariectomized rats when compared to the controls [5].…”

Osteogenic and anti-osteoporotic effects of risedronate-added calcium phosphate silicate cement

“…While CPC has a long history as a substitute to repair bone fractures, its insufficient mechanical strength in poorly vascularized regions always raises some concerns [11]. In our previous research, we attempted to deliver risedronate (RA), a third generation BP, from calcium silicate cement (CSC) [3], because CSC is more bioactive and has a higher compressive strength than CPC [12]. However, due to drawbacks of CSC (e.g.…”