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, Masahiro Anzai, T. Niino, Yasuyuki Sakai

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Article number035016
JournalBiofabrication
Volume8
Issue number3
DOIs
Publication statusPublished - 2016 Aug 30

Keywords

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

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biochemistry
  • Biomaterials
  • Biomedical Engineering

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