Novel integrative methodology for engineering large liver tissue equivalents based on three-dimensional scaffold fabrication and cellular aggregate assembly

Y. Pang, Y. Horimoto, S. Sutoko, K. Montagne, M. Shinohara, D. Mathiue, K. Komori, M. Anzai, T. Niino, Yasuyuki Sakai

Research output: Contribution to journalArticle

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Abstract

A novel engineering methodology for organizing a large liver tissue equivalent was established by intergrating both 'top down' and 'bottom up' approaches. A three-dimensional (3D) scaffold was engineered comprising 43 culture chambers (volume: 11.63 cm3) assembled in a symmetrical pattern on 3 layers, a design which enables further scaling up of the device to a clinically significant size (volume: 500 cm3). In addition, an inter-connected flow channel network was designed and proved to homogenously deliver culture medium to each chamber with the same pressure drop. After fabrication using nylon-12 and a selective laser sintering process, co-cultured cellular aggregates of human hepatoma Hep G2 and TMNK-1 cells were loosely packed into the culture chambers with biodegradable poly-L-lactic acid fibre pieces for 9 days of perfusion culture. The device enabled increased hepatic function and well-maintained cell viability, demonstrating the importance of an independent medium flow supply for cell growth and function provided by the current 3D scaffold. This integrative methodology from the macro- to the micro-scale provides an efficient way of arranging engineered liver tissue with improved mass transfer, making it possible to further scale up to a construct with clinically relevant size while maintaining high per-volume-based physiological function in the near future.

LanguageEnglish
Article number035016
JournalBiofabrication
Volume8
Issue number3
DOIs
StatePublished - 2016 Aug 30

Fingerprint

Scaffolds (biology)
Liver
Tissue
Fabrication
Scaffolds
Cell growth
Channel flow
Lactic acid
Pressure drop
Macros
Culture Media
Sintering
Mass transfer
Cells
Fibers
Lasers

Keywords

  • 3D scaffold
  • bottom up
  • implantable liver
  • perfusion culture
  • top down

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biochemistry
  • Biomaterials
  • Biomedical Engineering

Cite this

Novel integrative methodology for engineering large liver tissue equivalents based on three-dimensional scaffold fabrication and cellular aggregate assembly. / Pang, Y.; Horimoto, Y.; Sutoko, S.; Montagne, K.; Shinohara, M.; Mathiue, D.; Komori, K.; Anzai, M.; Niino, T.; Sakai, Yasuyuki.

In: Biofabrication, Vol. 8, No. 3, 035016, 30.08.2016.

Research output: Contribution to journalArticle

Pang, Y, Horimoto, Y, Sutoko, S, Montagne, K, Shinohara, M, Mathiue, D, Komori, K, Anzai, M, Niino, T & Sakai, Y 2016, 'Novel integrative methodology for engineering large liver tissue equivalents based on three-dimensional scaffold fabrication and cellular aggregate assembly' Biofabrication, vol 8, no. 3, 035016. DOI: 10.1088/1758-5090/8/3/035016
Pang, Y. ; Horimoto, Y. ; Sutoko, S. ; Montagne, K. ; Shinohara, M. ; Mathiue, D. ; Komori, K. ; Anzai, M. ; Niino, T. ; Sakai, Yasuyuki. / Novel integrative methodology for engineering large liver tissue equivalents based on three-dimensional scaffold fabrication and cellular aggregate assembly. In: Biofabrication. 2016 ; Vol. 8, No. 3.
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