title: Concentration- and time-dependent response of human gingival fibroblasts to fibroblast growth factor 2 immobilized on titanium dental implants.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Prosthetic Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Qianli
authors.initials: Q
authors.lastname: Ma
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Paul K
authors.initials: PK
authors.lastname: Chu
authors.forename: Shenglin
authors.initials: S
authors.lastname: Mei
authors.forename: Kun
authors.initials: K
authors.lastname: Ji
authors.forename: Lei
authors.initials: L
authors.lastname: Jin
authors.forename: Yumei
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible; D003758:Dental Implantation, Endosseous / Q000009:adverse effects; D016326:Extracellular Matrix Proteins / Q000235:genetics; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005881:Gingiva / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D055767:Immobilized Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D008422:Materials Testing; D053768:Metal Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D050997:Nanomedicine; D043942:Nanotubes / Q000737:chemistry / Q000648:ultrastructure; D016348:Osseointegration / Q000187:drug effects; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D013499:Surface Properties; D014025:Titanium
chemical_list: D020099:Coated Materials, Biocompatible; D016326:Extracellular Matrix Proteins; D055767:Immobilized Proteins; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D014025:Titanium