title: Sequential keratinocytic differentiation and maturation in a three-dimensional model of human artificial oral mucosa.
abstract: OBJECTIVE
  Oral mucosa shortage may limit or condition some clinical approaches in maxillofacial, periodontal and implant treatment. The availability of a human oral mucosa model generated by tissue engineering could help clinicians to address the lack of oral mucosa. In this work, we carried out a sequential maturation and differentiation study of the epithelial cell layer of an artificial human oral mucosa substitute based on fibrin-agarose biomaterials with fibroblasts and keratinocytes.
  
  
  METHODS
  Histological, immunohistochemical and gene expression analyses were carried out in artificial human oral mucosa models developed and cultured for 1, 2 and 3 wk.
  
  
  RESULTS
  Artificial oral mucosa models showed expression of tight junction proteins and cytokeratins from the first week of in vitro development. Mature samples of 3 wk of development subjected to air-liquid conditions showed signs of epithelial differentiation and expressed specific RNAs and proteins corresponding to adherent and gap junctions and basement lamina. Moreover, these mature samples overexpressed some desmosomal and tight junction transcripts, with gap junction components being downregulated.
  
  
  CONCLUSIONS
  These results suggest that bioengineered human oral mucosa substitutes form a well-developed epithelial layer that was very similar to human native tissues. In consequence, the epithelial layer could be fully functional in these oral mucosa substitutes, thus implying that these tissues may have clinical usefulness.
authors.affiliation: Department of Histology (Tissue Engineering Group), Faculty of Medicine, University of Granada, Granada, Spain.|Instituto de Investigación Biosanitaria ibs, Granada, Spain.|PhD Programme in Biomedicine, University of Granada, Granada, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Viñuela-Prieto
authors.affiliation: Department of Histology (Tissue Engineering Group), Faculty of Medicine, University of Granada, Granada, Spain.|Instituto de Investigación Biosanitaria ibs, Granada, Spain.
authors.forename: M C
authors.initials: MC
authors.lastname: Sánchez-Quevedo
authors.affiliation: Department of Histology (Tissue Engineering Group), Faculty of Medicine, University of Granada, Granada, Spain.|Instituto de Investigación Biosanitaria ibs, Granada, Spain.
authors.forename: C A
authors.initials: CA
authors.lastname: Alfonso-Rodríguez
authors.affiliation: Department of Histology (Tissue Engineering Group), Faculty of Medicine, University of Granada, Granada, Spain.|Instituto de Investigación Biosanitaria ibs, Granada, Spain.
authors.forename: A C
authors.initials: AC
authors.lastname: Oliveira
authors.affiliation: Department of Histology (Tissue Engineering Group), Faculty of Medicine, University of Granada, Granada, Spain.|Instituto de Investigación Biosanitaria ibs, Granada, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Scionti
authors.affiliation: Department of Histology (Tissue Engineering Group), Faculty of Medicine, University of Granada, Granada, Spain.|Instituto de Investigación Biosanitaria ibs, Granada, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: Martín-Piedra
authors.affiliation: Department of Stomatology, Faculty of Dentistry, University of Granada, Granada, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Moreu
authors.affiliation: Department of Histology (Tissue Engineering Group), Faculty of Medicine, University of Granada, Granada, Spain.|Instituto de Investigación Biosanitaria ibs, Granada, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Campos
authors.affiliation: Department of Histology (Tissue Engineering Group), Faculty of Medicine, University of Granada, Granada, Spain.|Instituto de Investigación Biosanitaria ibs, Granada, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Alaminos
authors.affiliation: Department of Histology (Tissue Engineering Group), Faculty of Medicine, University of Granada, Granada, Spain.|Instituto de Investigación Biosanitaria ibs, Granada, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Garzón
mesh_terms: D002454:Cell Differentiation; D005337:Fibrin; D005347:Fibroblasts; D006801:Humans; D015603:Keratinocytes; D009061:Mouth Mucosa; D012685:Sepharose; D023822:Tissue Engineering
chemical_list: D005337:Fibrin; D012685:Sepharose
keywords: artificial oral mucosa; desmosomes; intercellular junctions; laminin