Concentration- and time-dependent response of human gingival fibroblasts to fibroblast growth factor 2 immobilized on titanium dental implants

Int J Nanomedicine. 2012:7:1965-76. doi: 10.2147/IJN.S29538. Epub 2012 Apr 17.

Abstract

Background: Titanium (Ti) implants are widely used clinically, but peri-implantitis remains one of the most common and serious complications. Healthy integration between gingival tissue and the implant surface is critical to long-term success in dental implant therapy. The objective of this study was to investigate how different concentrations of immobilized fibroblast growth factor 2 (FGF2) on the titania nanotubular surface influence the response of human gingival fibroblasts (HGFs).

Methods: Pure Ti metal was anodized at 20 V to form a vertically organized titanium dioxide nanotube array on which three concentrations of FGF2 (250 ng/mL, 500 ng/mL, or 1000 ng/mL) were immobilized by repeated lyophilization. Surface topography was observed and FGF2 elution was detected using enzyme-linked immunosorbent assay. The bioactivity changes of dissolvable immobilized FGF2 were measured by methyl-thiazolyl-tetrazolium assay. Behavior of HGFs was evaluated using adhesion and methyl-thiazolyl-tetrazolium bromide assays.

Results: The FGF2 remained for several days on the modified surface on which HGFs were cultured. Over 90% of the dissolvable immobilized FGF2 had been eluted by Day 9, whereas the FGF2 activity was found to diminish gradually from Day 1 to Day 9. The titania nanotubular surface with an optimal preparing concentration (500 ng/mL) of FGF2 immobilization exhibited improved HGF functions such as cellular attachment, proliferation, and extracellular matrix-related gene expression. Moreover, significant bidirectional as well as concentration- and time-dependent bioactivity was observed.

Conclusion: Synergism of the FGF2-impregnated titanium dioxide nanotubular surface revealed good gingival-implant integration, indicating that these materials might have promising applications in dentistry and other biomedical devices.

Keywords: dental implants; extracellular matrix; fibroblast growth factor 2; real-time polymerase chain reaction; titanium dioxide nanotube.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Coated Materials, Biocompatible
  • Dental Implantation, Endosseous* / adverse effects
  • Extracellular Matrix Proteins / genetics
  • Fibroblast Growth Factor 2 / administration & dosage*
  • Fibroblast Growth Factor 2 / pharmacokinetics
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Gene Expression / drug effects
  • Gingiva / cytology*
  • Gingiva / drug effects*
  • Gingiva / metabolism
  • Humans
  • Immobilized Proteins / administration & dosage
  • Immobilized Proteins / pharmacokinetics
  • Materials Testing
  • Metal Nanoparticles / chemistry
  • Metal Nanoparticles / ultrastructure
  • Microscopy, Atomic Force
  • Microscopy, Electron, Scanning
  • Nanomedicine
  • Nanotubes / chemistry
  • Nanotubes / ultrastructure
  • Osseointegration / drug effects
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / pharmacokinetics
  • Surface Properties
  • Titanium*

Substances

  • Coated Materials, Biocompatible
  • Extracellular Matrix Proteins
  • Immobilized Proteins
  • Recombinant Proteins
  • Fibroblast Growth Factor 2
  • Titanium