Development of microstructured fish scale collagen scaffolds to manufacture a tissue-engineered oral mucosa equivalent

Ayako Suzuki, Hiroko Kato, Takahiro Kawakami, Yoshihiro Kodama, Mayuko Shiozawa, Hiroyuki Kuwae, Keito Miwa, Emi Hoshikawa, Kenta Haga, Aki Shiomi, Atsushi Uenoyama, Issei Saitoh, Haruaki Hayasaki, Jun Mizuno, Kenji Izumi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)


The present study aimed to develop a more biomimetic tissue-engineered oral mucosa equivalent comprising 1% type I tilapia scale collagen scaffold having microstructures mimicking the dermal–epidermal junction of oral mucosa and oral keratinocytes as graft materials for human use. We designed four micropattern prototypes mimicking the dermal–epidermal junction. Using a semiconductor process and soft lithography, negative molds were fabricated to develop microstructures using both polydimethylsiloxane and silicon substrates. Micropattern configurations of dermal–epidermal junctions manufactured from fish collagen consisting of a fibril network using our micropatterning system were well preserved, although the internal fibril network of the pillar pattern was sparse. Mixing 1% chondroitin sulfate with the collagen matrix minimized tissue-engineered oral mucosa equivalent contraction. Histologic examinations showed a flattening of the vertical dimensions of all microstructures and expansion of their pitches, indicating changes in the originally designed configurations. Nonetheless, histologic examinations revealed that a fully differentiated and stratified epithelial layer was developed on all scaffolds, suggesting that the microstructured fish scale collagen scaffolds have potential in the manufacturing of tissue-engineered oral mucosa equivalents for clinical use; however, enhancement of the mechanical properties of micropatterns is required. Our micropatterning technology can also apply to the development of oral mucosa in vitro models.

Original languageEnglish
Pages (from-to)578-600
Number of pages23
JournalJournal of Biomaterials Science, Polymer Edition
Issue number5
Publication statusPublished - 2020 Mar 23


  • Dermal–Epidermal Junction
  • Micropatterning
  • Oral Keratinocyte
  • Scaffold
  • Soft Lithography
  • Tilapia Scale Collagen

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Biomedical Engineering


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