title: Novel integrative methodology for engineering large liver tissue equivalents based on three-dimensional scaffold fabrication and cellular aggregate assembly.
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 cm(3)) 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 cm(3)). 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.
authors: Center for International Research on Integrative Biomedical Systems (CIBiS), Institute of Industrial Science, University of Tokyo, Komaba 4-6-1, Meguro-ku, Tokyo 153-8505, Japan.
authors: Y
authors: Y
authors: Pang
authors: Y
authors: Y
authors: Horimoto
authors: S
authors: S
authors: Sutoko
authors: K
authors: K
authors: Montagne
authors: M
authors: M
authors: Shinohara
authors: D
authors: D
authors: Mathiue
authors: K
authors: K
authors: Komori
authors: M
authors: M
authors: Anzai
authors: T
authors: T
authors: Niino
authors: Yasuyuki
authors: Y
authors: Sakai
mesh_terms: D000418:Albumins / Q000378:metabolism; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods*; D002460:Cell Line; D002470:Cell Survival; D018920:Coculture Techniques; D017076:Computer-Aided Design; D005947:Glucose / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D019164:Liver, Artificial; D008954:Models, Biological; D011091:Polyesters / Q000737:chemistry; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D000418:Albumins; D011091:Polyesters; C033616:poly(lactide); D005947:Glucose