Highly bioactive bone cement microspheres based on -tricalcium phosphate microparticles/mesoporous bioactive glass nanoparticles: Formulation, physico-chemical characterization and in vivo bone regeneration

Calcium phosphate cement (CPC) is a self-setting, biocompatible and osteoconductive bone cement, however its use as a bone substitute is still limited owing to its low bioactivity (i.e. its slow in vivo resorption and slow new bone formation rate) which is a challenging issue to be addressed. Herein, we report for the first time highly bioactive bone cement microspheres formulated from a cement paste containing alpha-tricalcium phosphate microparticles (alpha-TCP) and mesoporous calcium silicate bioactive glass nanoparticles (mesoporous BGn) using a water-in-oil emulsion method. Indeed, bioactive microspheres possess high potential as bone defect fillers for bone regeneration. The alpha-TCP microparticles were prepared by a solid state synthesis at 1400 oC while mesoporous BGn were synthesized by template-assissted ultrasound-mediated sol-gel method. The particle size distribution of as-prepared cement microspheres was in the range of 200 - 450 mu m with a sphericity index in the range of 0.92 - 0.94. The surface morphology of alpha-TCP microspheres revealed alpha-TCP micoparticles with smooth surfaces whereas alpha-TCP/BGn microspheres unveiled nano-roughened alpha-TCP microparticles. The as-prepared alpha-TCP/BGn cement microspheres exhibited larger specific surface area ca 18.6 m2/g, sustained release of soluble silicate (SiO44-) ions (118 ppm within a week) and high protein adsorption capacity (252 mg/g). Notably, the alpha-TCP/BGn cement microspheres showed excellent in vitro surface bioactivity via formation of massive amounts of bone-like hydroxyapatite spherules and aggregates on their surfaces after soaking in simulated body fluid. Importantly, the in vivo implantation of as-prepared alpha-TCP/BGn cement microspheres in rat calvarial critical size bone defects for 6 weeks unveiled high in vivo bioactivity in terms of substantial new bone ingrowth and significant new bone formation within the bone defect as evidenced by histological analyses, X-ray radiography and micro-computed tomography evaluations.