A nitrogen-containing bisphosphonate inhibits osteoblast attachment and impairs bone healing in bone-compatible scaffold.

Compromised osteoblast attachment on hydroxyapatite could be involved in the development of bone healing failure. We developed a bone-compatible scaffold that mimics bone structure with sub-micron hydroxyapatite (HA) surfaces, so that we could evaluate the effects of nitrogen-containing bisphosphonate (N-BP) on osteoblast behavior and bone healing. Human osteoblasts were seeded onto the bone-compatible scaffold with or without N-BP, and cell attachment and spreading behavior were evaluated 4 and 24 h after seeding. Then, mineralization was evaluated at 7 and 14 days. The osteoconductive activity of the scaffold was evaluated by implantation for 3 and 6 weeks into a rat cranial bone defect. The numbers of osteoblasts and their diameters were significantly less in N-BP-binding scaffolds than in untreated scaffolds at 4 and 24 h. Mineralization were also significantly less in the N-BP-binding scaffolds than in controls at 7 and 14 days. In vivo study revealed bone formation in N-BP-binding scaffolds was significantly less than in untreated scaffolds at 3 and 6 weeks. These results suggest that N-BP-binding to HA inhibited osteoblast attachment and spreading, thereby compromising bone healing process in the injured bone defect site.