title: Implant materials generate different peri-implant inflammatory factors: poly-ether-ether-ketone promotes fibrosis and microtextured titanium promotes osteogenic factors.
abstract: METHODS
  An in vitro study examining factors produced by human mesenchymal stem cells on spine implant materials.
  
  
  OBJECTIVE
  The aim of this study was to examine whether the inflammatory microenvironment generated by cells on titanium-aluminum-vanadium (Ti-alloy, TiAlV) surfaces is affected by surface microtexture and whether it differs from that generated on poly-ether-ether-ketone (PEEK).
  
  
  BACKGROUND
  Histologically, implants fabricated from PEEK have a fibrous connective tissue surface interface whereas Ti-alloy implants demonstrate close approximation with surrounding bone. Ti-alloy surfaces with complex micron/submicron scale roughness promote osteoblastic differentiation and foster a specific cellular environment that favors bone formation whereas PEEK favors fibrous tissue formation.
  
  
  METHODS
  Human mesenchymal stem cells were cultured on tissue culture polystyrene, PEEK, smooth TiAlV, or macro-/micro-/nano-textured rough TiAlV (mmnTiAlV) disks. Osteoblastic differentiation and secreted inflammatory interleukins were assessed after 7 days. Fold changes in mRNAs for inflammation, necrosis, DNA damage, or apoptosis with respect to tissue culture polystyrene were measured by low-density polymerase chain reaction array. Data were analyzed by analysis of variance, followed by Bonferroni's correction of Student's t-test.
  
  
  RESULTS
  Cells on PEEK upregulated mRNAs for chemokine ligand-2, interleukin (IL) 1β, IL6, IL8, and tumor necrosis factor. Cells grown on the mmnTiAlV had an 8-fold reduction in mRNAs for toll-like receptor-4. Cells grown on mmnTiAlV had reduced levels of proinflammatory interleukins. Cells on PEEK had higher mRNAs for factors strongly associated with cell death/apoptosis, whereas cells on mmnTiAlV exhibited reduced cytokine factor levels. All results were significant (P < 0.05).
  
  
  CONCLUSIONS
  These results suggest that fibrous tissue around PEEK implants may be due to several factors: reduced osteoblastic differentiation of progenitor cells and production of an inflammatory environment that favors cell death via apoptosis and necrosis. Ti alloy surfaces with complex macro/micro/nanoscale roughness promote osteoblastic differentiation and foster a specific cellular environment that favors bone formation.
  
  
  METHODS
  N/A.
authors.affiliation: *Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA †SpineCare Medical Group, San Francisco Spine Institute, San Francisco, CA ‡Titan Spine, LLC, Mequon, WI §Department of Periodontics, The University of Texas Health Science Center at San Antonio, San Antonio, TX; and ¶Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA.
authors.forename: Rene
authors.initials: R
authors.lastname: Olivares-Navarrete
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Hyzy
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Slosar
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Schneider
authors.forename: Zvi
authors.initials: Z
authors.lastname: Schwartz
authors.forename: Barbara D
authors.initials: BD
authors.lastname: Boyan
mesh_terms: D000497:Alloys; D017209:Apoptosis / Q000187:drug effects; D001577:Benzophenones; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology*; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology*; D002478:Cells, Cultured; D060833:Cellular Microenvironment; D004249:DNA Damage; D005355:Fibrosis / Q000139:chemically induced / Q000473:pathology; D006801:Humans; D007378:Interleukins / Q000032:analysis / Q000378:metabolism*; D007659:Ketones / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D011108:Polymers; D013499:Surface Properties; D014025:Titanium / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000497:Alloys; D001577:Benzophenones; D001672:Biocompatible Materials; D007378:Interleukins; D007659:Ketones; D011108:Polymers; C031462:titanium alloy (TiAl6V4); C063834:polyetheretherketone; D011092:Polyethylene Glycols; D014025:Titanium