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: Research - peer-reviewArticle

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
Pressure drop
Macros
Culture Media
Sintering
Mass transfer
Cells
Fibers
Lasers
nylon 12
poly(lactic acid)
Lactic acid

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: Research - peer-reviewArticle

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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