title: Nano-TiO2penetration of oral mucosa: in vitro analysis using 3D organotypic human buccal mucosa models.
abstract: BACKGROUND
  Oral cavity is a doorway for a variety of products containing titanium dioxide (TiO2) nanoparticles (NPs) (nano-TiO2) such as food additives, oral healthcare products and dental materials. Their potential to penetrate and affect normal human oral mucosa is not yet determined.
  
  
  OBJECTIVE
  To evaluate the ability of nano-TiO2to penetrate the in vitro reconstructed normal human buccal mucosa (RNHBM).
  
  
  METHODS
  RNHBM was generated from primary normal human oral keratinocytes and fibroblasts isolated from buccal oral mucosa of healthy patients (n = 6). The reconstructed tissues were exposed after 10 days to clinically relevant concentrations of spherical or spindle rutile nano-TiO2in suspension for short (20 min) and longer time (24 h). Ultrahigh-resolution imaging (URI) microscopy (CytoViva™, Auburn, AL, USA) was used to assess the depth of penetration into reconstructed tissues.
  
  
  RESULTS
  Ultrahigh-resolution imaging microscopy demonstrated the presence of nano-TiO2mostly in the epithelium of RNHBM at both 20 min and 24-h exposure, and this was shape and doze dependent at 24 h of exposure. The depth of penetration diminished in time at higher concentrations. The exposed epithelium showed increased desquamation but preserved thickness.
  
  
  CONCLUSIONS
  Nano-TiO2is able to penetrate RNHBM and to activate its barrier function in a doze- and time-dependent manner.
authors.affiliation: Department of Clinical Dentistry, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.|Gade Laboratory for Pathology, Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.|Department of Global Public Health and Primary Care, Centre for International Health, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
authors.forename: Victoria
authors.initials: V
authors.lastname: Konstantinova
authors.affiliation: Department of Clinical Dentistry, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.|Department of Global Public Health and Primary Care, Centre for International Health, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ibrahim
authors.affiliation: Department of Clinical Dentistry, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
authors.forename: Stein A
authors.initials: SA
authors.lastname: Lie
authors.affiliation: Department of Clinical Dentistry, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.|Gade Laboratory for Pathology, Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
authors.forename: Eivind Salmorin
authors.initials: ES
authors.lastname: Birkeland
authors.affiliation: Department of Oral Surgery, Institute of Clinical Dentistry, University of Bergen, Bergen, Norway.|Department of Ear-Nose-and-Throat Surgery, Haukeland University Hospital, Bergen, Norway.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Neppelberg
authors.affiliation: Department of Clinical Dentistry, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.|Oral Health Centre of Expertise in Western Norway, Hordaland, Norway.
authors.forename: Mihaela Cuida
authors.initials: MC
authors.lastname: Marthinussen
authors.affiliation: Gade Laboratory for Pathology, Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.|Department of Global Public Health and Primary Care, Centre for International Health, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.|Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Daniela Elena
authors.initials: DE
authors.lastname: Costea
authors.affiliation: Department of Clinical Dentistry, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
authors.forename: Mihaela R
authors.initials: MR
authors.lastname: Cimpan
mesh_terms: D006801:Humans; D066298:In Vitro Techniques; D053768:Metal Nanoparticles; D008853:Microscopy; D009061:Mouth Mucosa / Q000378:metabolism*; D010316:Particle Size; D010539:Permeability; D014025:Titanium / Q000493:pharmacokinetics*
chemical_list: C009495:titanium dioxide; D014025:Titanium
keywords: epithelium; nanoparticles; oral; organotypic model; titanium dioxide