BMP-2-coated mineral coated microparticles improve bone repair in atrophic non-unions

Eur Cell Mater. 2017 Jan 2:33:1-12. doi: 10.22203/eCM.v033a01.

Abstract

Atrophic non-unions are a major clinical problem. Mineral coated microparticles (MCM) are electrolyte-coated hydroxyapatite particles that have been shown in vitro to bind growth factors electrostatically and enable a tuneable sustained release. Herein, we studied whether MCM can be used in vivo to apply Bone Morphogenetic Protein-2 (BMP-2) to improve bone repair of atrophic non-unions. For this purpose, atrophic non-unions were induced in femurs of CD-1 mice (n = 48). Animals either received BMP-2-coated MCM (MCM + BMP; n = 16), uncoated MCM (MCM; n = 16) or no MCM (NONE; n = 16). Bone healing was evaluated 2 and 10 weeks postoperatively by micro-computed tomographic (µCT), biomechanical, histomorphometric and immunohistochemical analyses. µCT revealed more bone volume with more highly mineralised bone in MCM + BMP femurs. Femurs of MCM + BMP animals showed a significantly higher bending stiffness compared to other groups. Histomorphometry further demonstrated that the callus of MCM + BMP femurs was larger and contained more bone and less fibrous tissue. After 10 weeks, 7 of 8 MCM + BMP femurs presented with complete osseous bridging, whereas NONE femurs exhibited a non-union rate of 100 %. Of interest, immunohistochemistry could not detect macrophages within the callus, indicating a good biocompatibility of MCM. In conclusion, the local application of BMP-2-coated MCM improved bone healing in a challenging murine non-union model and, thus, should be of clinical interest in the treatment of non-unions.

MeSH terms

  • Animals
  • Biomechanical Phenomena / drug effects
  • Body Fluids / chemistry
  • Bone Morphogenetic Protein 2 / administration & dosage
  • Bone Morphogenetic Protein 2 / pharmacology*
  • Bone and Bones / drug effects
  • Bone and Bones / pathology
  • Bony Callus / drug effects
  • Bony Callus / pathology
  • Coated Materials, Biocompatible / administration & dosage
  • Coated Materials, Biocompatible / pharmacology*
  • Delayed-Action Preparations
  • Femur / diagnostic imaging
  • Femur / drug effects
  • Femur / pathology
  • Femur / physiopathology
  • Fracture Healing / drug effects*
  • Fractures, Ununited / pathology*
  • Fractures, Ununited / physiopathology
  • Immunohistochemistry
  • Kinetics
  • Mice
  • Microscopy, Electron, Scanning
  • Microspheres*
  • Minerals / pharmacology*
  • Osteotomy
  • X-Ray Microtomography

Substances

  • Bone Morphogenetic Protein 2
  • Coated Materials, Biocompatible
  • Delayed-Action Preparations
  • Minerals