Injectable chitosan microparticles incorporating bone morphogenetic protein-7 for bone tissue regeneration

J Biomed Mater Res A. 2014 Dec;102(12):4276-89. doi: 10.1002/jbm.a.35100. Epub 2014 Feb 14.

Abstract

This study investigates the influence of the controlled release of bone morphogenetic protein 7 (BMP-7) from cross-linked chitosan microparticles on pre-osteoblasts (OB-6) in vitro. BMP-7 was incorporated into microparticles by encapsulation during the particle preparation and coating after particle preparation. Chitosan microparticles had an average diameter of 700 µm containing ∼10-15 ng of BMP-7. The release study profile indicates that nearly 98% of the BMP-7 coated on the microparticles was released in a period of 18 days while only 36% of the BMP-7 encapsulated in the microparticles was released in the same time period. Cell attachment study indicated that the BMP-7 coated microparticles have many cells adhered on the microparticles in comparison with microparticles without growth factors on day 10. DNA assay indicated a statistical significant increase (p < 0.05) in the amount of DNA obtained from BMP-7 encapsulated and coated microparticles in comparison with microparticles without any growth factors. A real-time RT-PCR experiment was performed to determine the expression of a few osteoblast specific genes-Dlx5, runx2, osterix, osteopontin, osteocalcin, and bone sialoprotein. The results thus suggest that chitosan microparticles obtained by coacervation method are biocompatible and helps in improving the encapsulation efficiency of BMP-7. Also BMP-7 incorporated in the microparticles is being released in a controlled fashion to support attachment, proliferation and differentiation of pre-osteoblasts, thus acting as a good scaffold for bone tissue regeneration.

Keywords: BMP-7; chitosan; controlled release; in vitro; microparticles; osteoblasts.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antigens, Differentiation / biosynthesis
  • Bone Morphogenetic Protein 7* / chemistry
  • Bone Morphogenetic Protein 7* / pharmacology
  • Bone Regeneration / drug effects*
  • Cell Adhesion / drug effects
  • Cell Differentiation / drug effects*
  • Cell Line
  • Cell Proliferation / drug effects*
  • Chitosan
  • Delayed-Action Preparations / chemistry
  • Delayed-Action Preparations / pharmacology
  • Immobilized Proteins* / chemistry
  • Immobilized Proteins* / pharmacology
  • Materials Testing
  • Mice
  • Osteoblasts / cytology
  • Osteoblasts / metabolism*

Substances

  • Antigens, Differentiation
  • Bone Morphogenetic Protein 7
  • Delayed-Action Preparations
  • Immobilized Proteins
  • bmp7 protein, mouse
  • Chitosan