Sodium alendronate loaded poly(L-lactide-co-glycolide) microparticles immobilized on ceramic scaffolds for local treatment of bone defects

Abstract

Bone tissue regeneration in critical-size defects is possible after implantation of a three-dimensional scaffold and can be additionally enhanced once the scaffold is enriched with drugs or other factors supporting bone remodelling and healing. Sodium alendronate (Aln), a widely used anti-osteoporosis drug, exhibits strong inhibitory effect on bone resorption performed by osteoclasts. Thus we propose a new approach for the treatment of bone defects in craniofacial region combining biocompatible titanium dioxide (TiO2) scaffolds and poly(L-lactide-co-glycolide) (PLGA) microparticles (MPs) loaded with Aln. The MPs were effectively immobilized on the surface of the scaffolds’ pore walls by human recombinant collagen. Drug release from the scaffolds was characterised by initial burst (24 ± 6% of the drug released within first 24 h) followed by a sustained release phase (on average 5 µg of Aln released per day from day 3 to day 18). In vitro tests showed that Aln in concentrations of 5 µg/mL and 2.5 µg/mL was not cytotoxic for MG-63 osteoblast-like cells (viability between 81 ± 6% to 98 ± 3% of control) but it prevented RANKL-induced formation of osteoclast-like cells from macrophages derived from peripheral blood mononuclear cells (PBMCs), as shown by reduced fusion capability and decreased TRAP 5b activity (56 ± 5% reduction in comparison control after 8 days of culture). Results show that it is feasible to design the scaffolds providing required doses of Aln inhibiting osteoclastogenesis, reducing osteoclast activity, but not affecting osteoblast functions, which may be beneficial in the treatment of critical-size bone tissue defects.