The effect of immobilization of heparin and bone morphogenic protein-2 (BMP-2) to titanium surfaces on inflammation and osteoblast function

Biomaterials. 2011 Jan;32(2):366-73. doi: 10.1016/j.biomaterials.2010.09.008. Epub 2010 Sep 28.

Abstract

The aim of this study was to investigate biologic function of bone morphorgenic protein-2 (rhBMP-2) immobilized on the heparin-grafted Ti surface. Ti surfaces were first modified by 3-aminopropyltriethoxysilane (ATPES), followed by grafting of heparin. BMP-2 was then immobilized on the heparin-grafted Ti surfaces. Pristine Ti and functionalized Ti surfaces were characterized by X-ray photoelectron spectroscopy (XPS), measurement of water contact angles, and protein adsorption. The biological activity of MG-63 cells on pristine and functionalized Ti surfaces was investigated by cell proliferation assays, measurement of alkaline phosphate (ALP) activity, and determination of calcium deposition. Anti-inflammatory effects were assessed by RT-PCR to measure the transcript levels of IL-6 and TNF-α. XPS revealed that heparin and BMP-2 were successfully grafted and immobilized on the Ti surfaces, respectively. In addition, Ti surfaces with BMP-2 immobilized were more hydrophilic than pristine Ti. Furthermore, BMP-2 immobilized Ti promoted significantly higher ALP activity and calcium deposition by MG-63 cells than pristine Ti. The inflammatory response was also decreased when cells were grown on heparin-grafted, BMP-2-immobilized Ti surfaces. The results of this study suggest that by grafting heparin and immobilizing BMP-2 on Ti surfaces, inflammation can be inhibited and osteoblast function promoted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Bone Morphogenetic Protein 2 / chemistry
  • Bone Morphogenetic Protein 2 / immunology*
  • Bone Morphogenetic Protein 2 / pharmacology*
  • Calcium / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Heparin / chemistry
  • Heparin / immunology*
  • Heparin / pharmacology*
  • Humans
  • Interleukin-6 / genetics
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Microscopy, Electron, Scanning
  • NIH 3T3 Cells
  • Osteoblasts / cytology
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism*
  • Photoelectron Spectroscopy
  • Reverse Transcriptase Polymerase Chain Reaction
  • Titanium / chemistry*
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Bone Morphogenetic Protein 2
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Heparin
  • Titanium
  • Alkaline Phosphatase
  • Calcium