Bioabsorbable bone plates enabled with local, sustained delivery of alendronate for bone regeneration

We prepared a bone plate enabled with the local, sustained release of alendronate, which is a drug known to inhibit osteoclast-mediated bone resorption and also expedite the bone-remodeling activity of osteoblasts. For this, we coated a bone plate already in clinical use (PLT-1031, Inion, Finland) with a blend of alendronate and a biocompatible polymer, azidobenzoic acid-modified chitosan (i.e., Az-CH) photo-crosslinked by UV irradiation. As we performed the in vitro drug release study, the drug was released from the coating at an average rate of 4.03 mu g/day for 63 days in a sustained manner. To examine the effect on bone regeneration, the plate was fixed on an 8 mm cranial critical size defect in living rats and the newly formed bone volume was quantitatively evaluated by micro-computed tomography (micro-CT) at scheduled times over 8 weeks. At week 8, the group implanted with the plate enabled with sustained delivery of alendronate showed a significantly higher volume of newly formed bone (52.78 +/- 6.84%) than the groups implanted with the plates without drug (23.6 +/- 3.81%) (p < 0.05). The plate enabled with alendronate delivery also exhibited good biocompatibility on H&E staining, which was comparable to the Inion plate already in clinical use. Therefore, we suggest that a bone plate enabled with local, sustained delivery of alendronate can be a promising system with the combined functionality of bone fixation and its expedited repair. (C) 2015 Elsevier B.V. All rights reserved.