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J Funct Biomater. 2020 Feb 28;11(1). pii: E13. doi: 10.3390/jfb11010013.

Liver Bioreactor Design Issues of Fluid Flow and Zonation, Fibrosis, and Mechanics: A Computational Perspective.

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Department of Physical Sciences, MacEwan University, Edmonton, AB T5J 4S2, Canada.
Computer Modelling Group Ltd, Calgary, AB T2L 2A6, Canada.
Department of Physics and Experimental Oncology, University of Alberta, Edmonton, AB T6G 2J1, Canada.
DIMEAS, Politecnico di Torino, Corso Duca degli Abruzzi 24, Torino, 10129, TO, Italy.


Tissue engineering, with the goal of repairing or replacing damaged tissue and organs, has continued to make dramatic science-based advances since its origins in the late 1980's and early 1990's. Such advances are always multi-disciplinary in nature, from basic biology and chemistry through physics and mathematics to various engineering and computer fields. This review will focus its attention on two topics critical for tissue engineering liver development: (a) fluid flow, zonation, and drug screening, and (b) biomechanics, tissue stiffness, and fibrosis, all within the context of 3D structures. First, a general overview of various bioreactor designs developed to investigate fluid transport and tissue biomechanics is given. This includes a mention of computational fluid dynamic methods used to optimize and validate these designs. Thereafter, the perspective provided by computer simulations of flow, reactive transport, and biomechanics responses at the scale of the liver lobule and liver tissue is outlined, in addition to how bioreactor-measured properties can be utilized in these models. Here, the fundamental issues of tortuosity and upscaling are highlighted, as well as the role of disease and fibrosis in these issues. Some idealized simulations of the effects of fibrosis on lobule drug transport and mechanics responses are provided to further illustrate these concepts. This review concludes with an outline of some practical applications of tissue engineering advances and how efficient computational upscaling techniques, such as dual continuum modeling, might be used to quantify the transition of bioreactor results to the full liver scale.


drug transport; dual continuum modeling; fibrosis; lobule; multi-scale modeling; tissue engineering; upscaling; virtual liver; zonation

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