title: Oxidized Titanium Implants Enhance Osseointegration via Mechanisms Involving RANK/RANKL/OPG Regulation.
abstract: BACKGROUND
  The role of implant surface properties for bone formation and bone remodeling, that is, the major events during osseointegration, are incompletely understood.
  
  
  OBJECTIVE
  This experimental study aimed to investigate the relation between molecular and morphological patterns at the bone interface for machined and oxidized implants.
  
  
  METHODS
  Machined and anodically oxidized titanium implants were inserted in rat tibiae. The implants and surrounding tissue were retrieved at 1, 3, 6, 14, or 28 days for gene expression, histology, histomorphometry, backscatter scanning electron microscopy, and transmission electron microscopy.
  
  
  RESULTS
  Compared with machined-surface implants, a higher degree of mineralized bone was found in contact with the oxidized-surface implants. After 3 days, cells adherent to the oxidized implants demonstrated a markedly higher expression of receptor activator of nuclear factor kappa-B (RANK), receptor activator of nuclear factor kappa-B ligand (RANKL), and osteoprotegerin (OPG). Whereas the OPG expression was higher at the machined implants at 6, 14, and 28 days, a higher RANKL/OPG ratio was detected at the oxidized implants. Between 3 and 14 days, both implants demonstrated a temporal increase in RANKL/OPG, corresponding to the remodeling phase at the bone-implant interface. For both implant types, the RANKL/OPG ratio sharply decreased to a low level after 28 days.
  
  
  CONCLUSIONS
  The present results show that oxidized implants rapidly promote a high degree of mineralized bone apposition to the surface. As determined by the gene expression data, the mechanisms involve an early induction of osteoclastic differentiation and subsequently more intensive bone remodeling, which accelerates the maturation of the bone-implant interface. The present study suggests that the RANKL/OPG ratio is a sensitive indicator for monitoring the remodeling process during osseointegration.
authors.affiliation: BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Lennerås
authors.affiliation: BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Palmquist
authors.affiliation: BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
authors.forename: Birgitta
authors.initials: B
authors.lastname: Norlindh
authors.affiliation: BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Emanuelsson
authors.affiliation: BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Thomsen
authors.affiliation: BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
authors.forename: Omar
authors.initials: O
authors.lastname: Omar
mesh_terms: D000818:Animals; D000069343:Bone-Implant Interface; D015870:Gene Expression; D008855:Microscopy, Electron, Scanning; D016348:Osseointegration / Q000187:drug effects*; D053244:Osteoprotegerin / Q000378:metabolism*; D019736:Prostheses and Implants; D053245:RANK Ligand / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism*; D013499:Surface Properties; D014025:Titanium / Q000378:metabolism*
chemical_list: D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C009495:titanium dioxide; D014025:Titanium
keywords: bone remodeling; bone-implant interface; gene expression; osseointegration