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

J Control Release. 2016 Jan 28:222:97-106. doi: 10.1016/j.jconrel.2015.12.007. Epub 2015 Dec 9.

Abstract

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 4.03μg/day for 63days in a sustained manner. To examine the effect on bone regeneration, the plate was fixed on an 8mm 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 8weeks. 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.

Keywords: Alendronate; Bioabsorbable bone plate; Bone regeneration; Drug delivery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorbable Implants
  • Alendronate / administration & dosage*
  • Alendronate / chemistry
  • Alendronate / therapeutic use
  • Animals
  • Bone Density Conservation Agents / administration & dosage*
  • Bone Density Conservation Agents / chemistry
  • Bone Density Conservation Agents / therapeutic use
  • Bone Plates*
  • Bone Regeneration / drug effects*
  • Cell Line
  • Cell Line, Tumor
  • Chitosan / analogs & derivatives
  • Chitosan / chemistry
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / chemistry
  • Delayed-Action Preparations / therapeutic use
  • Drug Liberation
  • Humans
  • Male
  • Mice
  • Rats, Sprague-Dawley
  • Skull / drug effects
  • Skull / injuries
  • Skull / pathology
  • Skull / physiology

Substances

  • Bone Density Conservation Agents
  • Delayed-Action Preparations
  • Chitosan
  • Alendronate