title: Early molecular assessment of osseointegration in humans.
abstract: OBJECTIVE
  To determine the early temporal-wide genome transcription regulation by the surface topography at the bone-implant interface of implants bearing microroughened or superimposed nanosurface topology.
  
  
  METHODS
  Four commercially pure titanium implants (2.2 × 5.0 mm) with either a moderately roughened surface (TiOblast) or super-imposed nanoscale topography (Osseospeed) were placed (n = 2/surface) in edentulous sites of eleven systemically healthy subjects and subsequently removed after 3 and 7 days. Total RNA was isolated from cells adherent to retrieved implants. A whole-genome microarray using the Affymetrix Human gene 1.1 ST Array was used to describe the gene expression profiles that were differentially regulated by the implant surfaces.
  
  
  RESULTS
  There were no significant differences when comparing the two implant surfaces at each time point. However, the microarray identified several genes that were differentially regulated at day 7 vs. day 3 for both implant surfaces. Functionally relevant categories related to the extracellular matrix (ECM), collagen fibril organization, and angiogenesis were upregulated at both surfaces (day7 vs. day3). Abundant upregulation of several differential markers of alternative activated macrophages was observed (e.g., MRC1, MSR1, MS4A4A, SLC38A6, and CCL18). The biological processes involved with the inflammatory/immune response gene expression were concomitantly downregulated.
  
  
  CONCLUSIONS
  Gene regulation implicating collagen fibrillogenesis and ECM organization as well as the inflammatory/immune responses involving the alternative activated pathway are observed in implant adherent cells at early (3-7 days) after implantation. These gene expression events may indicate a pivotal role of collagen fibrillogenesis as well as immunomodulation in altering bone accrual and biomechanical physical properties of the implant-bone interface.
authors.affiliation: Department of Prosthodontics, University of Iowa, Iowa City, IA, USA.
authors.forename: Ghadeer N
authors.initials: GN
authors.lastname: Thalji
authors.affiliation: Department of Periodontics, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Salvador
authors.initials: S
authors.lastname: Nares
authors.affiliation: Department of Prosthodontics, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Lyndon F
authors.initials: LF
authors.lastname: Cooper
mesh_terms: D000368:Aged; D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics; D018951:Antigens, CD20 / Q000235:genetics; D015415:Biomarkers / Q000032:analysis; D000069343:Bone-Implant Interface / Q000033:anatomy & histology*; D019742:Chemokines, CC / Q000235:genetics; D003094:Collagen / Q000235:genetics; D015921:Dental Implants; D003764:Dental Materials / Q000737:chemistry; D017267:Dental Prosthesis Design; D005109:Extracellular Matrix / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008262:Macrophage Activation / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D016348:Osseointegration / Q000235:genetics*; D011971:Receptors, Immunologic / Q000235:genetics; D051117:Scavenger Receptors, Class A / Q000235:genetics; D013499:Surface Properties; D014025:Titanium / Q000737:chemistry; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D026921:Amino Acid Transport Systems, Neutral; D018951:Antigens, CD20; D015415:Biomarkers; C111792:CCL18 protein, human; D019742:Chemokines, CC; D015921:Dental Implants; D003764:Dental Materials; C573543:MRC1 protein, human; C424714:MS4A4A protein, human; C495139:MSR1 protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D051117:Scavenger Receptors, Class A; D003094:Collagen; D014025:Titanium
keywords: biomaterials; bone implant interactions; wound healing