title: Differential response of human gingival fibroblasts to titanium- and titanium-zirconium-modified surfaces.
abstract: OBJECTIVE
  Gingival fibroblasts are responsible for the constant adaptation, wound healing and regeneration of gingival connective tissue. New titanium-zirconium (TiZr) abutment surfaces have been designed to improve soft tissue integration and reduce implant failure compared with titanium (Ti). The aim of the present study was first to characterize a primary human gingival fibroblast (HGF) model and secondly to evaluate their differential response to Ti and TiZr polished (P), machined (M) and machined + acid-etched (modMA) surfaces, respectively.
  
  
  METHODS
  HGF were cultured on tissue culture plastic or on the different Ti and TiZr surfaces. Cell morphology was evaluated through confocal and scanning electron microscopy. A wound healing assay was performed to evaluate the capacity of HGF to close a scratch. The expression of genes was evaluated by real-time RT-PCR, addressing: (i) extracellular matrix organization and turnover; (ii) inflammation; (iii) cell adhesion and structure; and (iv) wound healing. Finally, cells on Ti/TiZr surfaces were immunostained with anti-ITGB3 antibodies to analyze integrin β3 production. Matrix metalloproteinase-1 (MMP1) and inhibitor of metallopeptidases-1 (TIMP1) production were analyzed by enzyme-linked immunosorbent assays.
  
  
  RESULTS
  On tissue culture plastic, HGF showed no differences between donors on cell proliferation and on the ability for wound closure; α-smooth muscle actin was overexpressed on scratched monolayers. The differentiation profile showed increased production of extracellular matrix components. Ti and TiZr showed similar biocompatibility with HGF. TiZr increased integrin-β3 mRNA and protein levels, compared with Ti. Cells on TiZr surfaces showed higher MMP1 protein than Ti surfaces, although similar TIMP1 protein production. In this in vitro experiment, P and M surfaces from both Ti and TiZr showed better HGF growth than modMA.
  
  
  CONCLUSIONS
  Taking into account the better mechanical properties and bioactivity of TiZr compared with Ti, the results of the present study show that TiZr is a potential clinical candidate for soft tissue integration and implant success.
authors.affiliation: Department of Fundamental Biology and Health Sciences, Research Institute on Health Sciences (IUNICS), University of Balearic Islands, Palma de Mallorca, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Gómez-Florit
authors.forename: J M
authors.initials: JM
authors.lastname: Ramis
authors.forename: R
authors.initials: R
authors.lastname: Xing
authors.forename: S
authors.initials: S
authors.lastname: Taxt-Lamolle
authors.forename: H J
authors.initials: HJ
authors.lastname: Haugen
authors.forename: S P
authors.initials: SP
authors.lastname: Lyngstadaas
authors.forename: M
authors.initials: M
authors.lastname: Monjo
mesh_terms: D000134:Acid Etching, Dental / Q000379:methods; D000199:Actins / Q000032:analysis; D001672:Biocompatible Materials / Q000737:chemistry; D002448:Cell Adhesion / Q000502:physiology; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D048430:Cell Shape / Q000502:physiology; D002478:Cells, Cultured; D045662:Dental Etching / Q000379:methods; D003764:Dental Materials / Q000737:chemistry*; D003775:Dental Polishing / Q000379:methods; D016326:Extracellular Matrix Proteins / Q000032:analysis; D005347:Fibroblasts / Q000502:physiology*; D005881:Gingiva / Q000166:cytology / Q000502:physiology*; D006801:Humans; D039661:Integrin beta3 / Q000032:analysis; D008422:Materials Testing; D020781:Matrix Metalloproteinase 1 / Q000032:analysis; D008855:Microscopy, Electron, Scanning; D013499:Surface Properties; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis; D014025:Titanium / Q000737:chemistry*; D015040:Zirconium / Q000737:chemistry*
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D001672:Biocompatible Materials; D003764:Dental Materials; D016326:Extracellular Matrix Proteins; C061248:ITGB3 protein, human; D039661:Integrin beta3; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D015040:Zirconium; D014025:Titanium; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1
keywords: primary human gingival fibroblasts; soft tissue; titanium; titanium-zirconium