In situ cross-linked electrospun fiber scaffold of collagen for fabricating cell-dense muscle tissue

Naoya Takeda*, Kenichi Tamura, Ryo Mineguchi, Yumiko Ishikawa, Yuji Haraguchi, Tatsuya Shimizu, Yusuke Hara

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)


Engineered muscle tissues used as transplant tissues in regenerative medicine should have a three-dimensional and cell-dense structure like native tissue. For fabricating a 3D cell-dense muscle tissue from myoblasts, we proposed the electrospun type I collagen microfiber scaffold of the string-shape like a harp. The microfibers were oriented in the same direction to allow the myoblasts to align, and were strung at low density with micrometer intervals to create space for the cells to occupy. To realize this shape of the scaffold, we employed in situ cross-linking during electrospinning process for the first time to collagen fibers. The collagen microfibers in situ cross-linked with glutaraldehyde stably existed in the aqueous media and completely retained the original shape to save the spaces between the fibers for over 14 days. On the contrary, the conventional cross-linking method by exposure to a glutaraldehyde aqueous solution vapor partially dissolved and damaged the fiber to lose a low-density shape of the scaffold. Myoblasts could penetrate into the interior of the in situ cross-linked string-shaped scaffold and form the cell-dense muscle tissues. Histochemical analysis showed the total area occupied by the cells in the cross section of the tissue was approximately 73 %. Furthermore, the resulting muscle tissue fabricated from primary myoblasts showed typical sarcomeric cross-striations and the entire tissue continuously pulsated by autonomous contraction. Together with the in situ cross-linking, the string-shaped scaffold provides an efficient methodology to fabricate a cell-dense 3D muscle tissue, which could be applied in regenerative medicine in future.

Original languageEnglish
Pages (from-to)141-148
Number of pages8
JournalJournal of Artificial Organs
Issue number2
Publication statusPublished - 2016 Jun 1


  • Cell-dense muscle tissue
  • Electrospinning
  • In situ cross-link
  • String-shaped scaffold

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biomaterials
  • Biomedical Engineering
  • Cardiology and Cardiovascular Medicine


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