Construction and characterization of a tissue-engineered oral mucosa equivalent based on a chitosan-fish scale collagen composite

J Biomed Mater Res B Appl Biomater. 2012 Oct;100(7):1792-802. doi: 10.1002/jbm.b.32746. Epub 2012 Jul 18.

Abstract

This study was designed to (1) assess the in vitro biocompatibility of a chitosan-collagen composite scaffold (C3) constructed by blending commercial chitosan and tilapia scale collagen with oral mucosa keratinocytes, (2) histologically and immunohistochemically characterize an ex vivo-produced oral mucosa equivalent constructed using the C3 (EVPOME-C), and (3) compare EVPOME-C with oral mucosa constructs utilizing AlloDerm® (EVPOME-A), BioMend® Extend™ (EVPOME-B), and native oral mucosa. C3 scaffold had a well-developed fibril network and a sufficiently small porosity to prevent keratinocytes from growing inside the scaffold after cell-seeding. The EVPOME oral mucosa constructs were fabricated in a chemically defined culture system. After culture at an air-liquid interface, EVPOME-C and EVPOME-B had multilayered epithelium with keratinization, while EVPOME-A had a more organized stratified epithelium. Ki-67 and p63 immunolabeled cells in the basal layer of all EVPOMEs suggested a regenerative ability. Compared with native oral mucosa, the keratin 15 and 10/13 expression patterns in all EVPOMEs showed a less-organized differentiation pattern. In contrast to the β1-integrin and laminin distribution in EVPOME-A and native oral mucosa, the subcellular deposition in EVPOME-C and EVPOME-B indicated that complete basement membrane formation failed. These findings demonstrated that C3 has a potential application for epithelial tissue engineering and provides a new potential therapeutic device for oral mucosa regenerative medicine.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Animal Structures / chemistry*
  • Animals
  • Cells, Cultured
  • Chitosan / chemistry*
  • Collagen / chemistry*
  • Female
  • Fish Proteins / chemistry*
  • Humans
  • Keratin-10 / metabolism
  • Keratin-13 / metabolism
  • Keratin-15 / metabolism
  • Keratinocytes* / cytology
  • Keratinocytes* / metabolism
  • Ki-67 Antigen / metabolism
  • Male
  • Mouth Mucosa* / cytology
  • Mouth Mucosa* / metabolism
  • Tilapia*
  • Tissue Engineering*
  • Transcription Factors / metabolism
  • Tumor Suppressor Proteins / metabolism

Substances

  • Fish Proteins
  • KRT10 protein, human
  • KRT13 protein, human
  • KRT15 protein, human
  • Keratin-13
  • Keratin-15
  • Ki-67 Antigen
  • TP63 protein, human
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Keratin-10
  • Collagen
  • Chitosan