The Effect of Alendronate Loaded Biphasic Calcium Phosphate Scaffolds on Bone Regeneration in a Rat Tibial Defect Model

Int J Mol Sci. 2015 Nov 6;16(11):26738-53. doi: 10.3390/ijms161125982.

Abstract

This study investigated the effect of alendronate (Aln) released from biphasic calcium phosphate (BCP) scaffolds. We evaluated the in vitro osteogenic differentiation of Aln/BCP scaffolds using MG-63 cells and the in vivo bone regenerative capability of Aln/BCP scaffolds using a rat tibial defect model with radiography, micro-computed tomography (CT), and histological examination. In vitro studies included the surface morphology of BCP and Aln-loaded BCP scaffolds visualized using field-emission scanning electron microscope, release kinetics of Aln from BCP scaffolds, alkaline phosphatase (ALP) activity, calcium deposition, and gene expression. The in vitro studies showed that sustained release of Aln from the BCP scaffolds consisted of porous microstructures, and revealed that MG-63 cells cultured on Aln-loaded BCP scaffolds showed significantly increased ALP activity, calcium deposition, and gene expression compared to cells cultured on BCP scaffolds. The in vivo studies using radiograph and histology examination revealed abundant callus formation and bone maturation at the site in the Aln/BCP groups compared to the control group. However, solid bony bridge formation was not observed at plain radiographs until 8 weeks. Micro-CT analysis revealed that bone mineral density and bone formation volume were increased over time in an Aln concentration-dependent manner. These results suggested that Aln/BCP scaffolds have the potential for controlling the release of Aln and enhance bone formation and mineralization.

Keywords: alendronate; biphasic calcium phosphate; bone formation; scaffold.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alendronate / pharmacokinetics
  • Alendronate / pharmacology*
  • Alkaline Phosphatase / metabolism
  • Animals
  • Bone Density Conservation Agents / pharmacokinetics
  • Bone Density Conservation Agents / pharmacology*
  • Bone Regeneration / drug effects*
  • Bone Regeneration / physiology
  • Calcification, Physiologic / drug effects
  • Cell Differentiation / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Delayed-Action Preparations
  • Dose-Response Relationship, Drug
  • Drug Liberation
  • Humans
  • Hydroxyapatites / chemistry*
  • Osteoblasts / cytology
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism
  • Osteogenesis / drug effects*
  • Osteogenesis / physiology
  • Porosity
  • Rats
  • Rats, Sprague-Dawley
  • Tibia / drug effects
  • Tibia / injuries
  • Tissue Engineering
  • Tissue Scaffolds*
  • X-Ray Microtomography

Substances

  • Bone Density Conservation Agents
  • Delayed-Action Preparations
  • Hydroxyapatites
  • hydroxyapatite-beta tricalcium phosphate
  • Alkaline Phosphatase
  • Alendronate