title: Rough titanium alloys regulate osteoblast production of angiogenic factors.
abstract: BACKGROUND
  Polyether-ether-ketone (PEEK) and titanium-aluminum-vanadium (titanium alloy) are used frequently in lumbar spine interbody fusion. Osteoblasts cultured on microstructured titanium generate an environment characterized by increased angiogenic factors and factors that inhibit osteoclast activity mediated by integrin α2β1 signaling. It is not known if this is also true of osteoblasts on titanium alloy or PEEK.
  
  
  OBJECTIVE
  The purpose of this study was to determine if osteoblasts generate an environment that supports angiogenesis and reduces osteoclastic activity when grown on smooth titanium alloy, rough titanium alloy, or PEEK.
  
  
  METHODS
  This in vitro study compared angiogenic factor production and integrin gene expression of human osteoblast-like MG63 cells cultured on PEEK or titanium-aluminum-vanadium (titanium alloy).
  
  
  METHODS
  MG63 cells were grown on PEEK, smooth titanium alloy, or rough titanium alloy. Osteogenic microenvironment was characterized by secretion of osteoprotegerin and transforming growth factor beta-1 (TGF-β1), which inhibit osteoclast activity and angiogenic factors including vascular endothelial growth factor A (VEGF-A), fibroblast growth factor 2 (FGF-2), and angiopoietin-1 (ANG-1). Expression of integrins, transmembrane extracellular matrix recognition proteins, was measured by real-time polymerase chain reaction.
  
  
  RESULTS
  Culture on titanium alloy stimulated osteoprotegerin, TGF-β1, VEGF-A, FGF-2, and angiopoietin-1 production, and levels were greater on rough titanium alloy than on smooth titanium alloy. All factors measured were significantly lower on PEEK than on smooth or rough titanium alloy. Culture on titanium alloy stimulated expression of messenger RNA for integrins that recognize Type I collagen in comparison with PEEK.
  
  
  CONCLUSIONS
  Rough titanium alloy stimulated cells to create an osteogenic-angiogenic microenvironment. The osteogenic-angiogenic responses to titanium alloy were greater than PEEK and greater on rough titanium alloy than on smooth titanium alloy. Surface features regulated expression of integrins important in collagen recognition. These factors may increase bone formation, enhance integration, and improve implant stability in interbody spinal fusions.
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Georgia Institute of Technology, 315 Ferst Drive NW, Atlanta, GA 30332-0363, USA.
authors.forename: Rene
authors.initials: R
authors.lastname: Olivares-Navarrete
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Hyzy
authors.forename: Rolando A
authors.initials: RA
authors.lastname: Gittens
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Schneider
authors.forename: David A
authors.initials: DA
authors.lastname: Haithcock
authors.forename: Peter F
authors.initials: PF
authors.lastname: Ullrich
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Slosar
authors.forename: Zvi
authors.initials: Z
authors.lastname: Schwartz
authors.forename: Barbara D
authors.initials: BD
authors.lastname: Boyan
mesh_terms: D000497:Alloys / Q000494:pharmacology; D042683:Angiopoietin-1 / Q000378:metabolism*; D001577:Benzophenones; D001672:Biocompatible Materials; D002460:Cell Line; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006801:Humans; D007659:Ketones / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D053244:Osteoprotegerin / Q000378:metabolism; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011108:Polymers; D014025:Titanium / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D000497:Alloys; D042683:Angiopoietin-1; D001577:Benzophenones; D001672:Biocompatible Materials; D007659:Ketones; D053244:Osteoprotegerin; D011108:Polymers; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; C063834:polyetheretherketone; D011092:Polyethylene Glycols; D014025:Titanium
keywords: Angiogenesis; Osteoblast; PEEK; Polyether-ether-ketone; Titanium-aluminum-vanadium alloy