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.

羟基磷灰石受损的成骨细胞附着可能参与骨愈合失败的发展。我们开发了一种与骨相容的支架，该支架可模拟具有亚微米羟基磷灰石（HA）表面的骨骼结构，以便我们可以评估含氮双膦酸盐（N-BP）对成骨细胞行为和骨愈合的影响。将人类成骨细胞接种到有或没有N-BP的骨相容性支架上，并在接种后4和24 h评估细胞附着和扩散行为。然后，在7天和14天评估矿化程度。通过在大鼠颅骨缺损中植入3周和6周来评估支架的骨传导活性。在N和BP结合的支架上成骨细胞的数量和直径显着小于未经处理的支架在4和24小时。在7天和14天时，N-BP结合支架的矿化作用也显着低于对照组。体内研究表明，在3周和6周时，N-BP结合支架的骨形成明显少于未处理的支架。这些结果表明，N-BP与HA的结合抑制了成骨细胞的附着和扩散，从而损害了受损骨缺损部位的骨愈合过程。