Bisphosphonate activation of crystallized bioglass scaffolds for enhanced bone formation

The interplay between bone formation by osteoblasts and bone resorption by osteoclasts has a critical effect on bone remodelling processes, and resultant bone quality. Bone scaffolds combined with anti-resorptive bisphosphonate drugs are a promising approach to achieving bone regeneration. Here, we have examined the synergistic effects of the bisphosphonate alendronate (ALD) coated onto calcium phosphate (CaP) modified, sintered bioactive glass 45S5 (BG) scaffolds, on osteoblast stimulation and osteoclast inhibition. After BG pre-treatment with ALD (10^-8 M) for 5 days, human MG-63 osteoblasts displayed increased cellular proliferation and significantly enhanced alkaline phosphatase activity (ALP), in comparison with a non-ALD control BG. In contrast, human THP-1-derived osteoclasts cultured with 10^-8 M ALD pretreated BG scaffolds showed a significant decrease in tartrate-resistant acid phosphatase (TRAcP) activity, and morphological changes indicative of functional inhibition, including reduced cell size and disruption of the osteoclast sealing zone (F-actin rings). These findings indicate that ALD-coated BG scaffolds promote osteoblast activity and inhibit osteoclast function to enhance bone formation.