Journal
TISSUE ENGINEERING PART C-METHODS
Volume 19, Issue 11, Pages 875-884Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/ten.tec.2012.0700
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Funding
- National Institutes of Health [5R21DK077802]
- National Science Foundation [DMR 090750, CBET 0933225, DBI 1062380]
- US EPA [R834998]
- ICTAS Center for Systems Biology of Engineered Tissues, Virginia Tech
- EPA [150257, R834998] Funding Source: Federal RePORTER
- Direct For Biological Sciences
- Div Of Biological Infrastructure [1062380] Funding Source: National Science Foundation
- Directorate For Engineering
- Div Of Chem, Bioeng, Env, & Transp Sys [0933225] Funding Source: National Science Foundation
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The design of in vitro models that mimic the stratified multicellular hepatic microenvironment continues to be challenging. Although several in vitro hepatic cultures have been shown to exhibit liver functions, their physiological relevance is limited due to significant deviation from in vivo cellular composition. We report the assembly of a novel three-dimensional (3D) organotypic liver model incorporating three different cell types (hepatocytes, liver sinusoidal endothelial cells, and Kupffer cells) and a polymeric interface that mimics the Space of Disse. The nanoscale interface is detachable, optically transparent, derived from self-assembled polyelectrolyte multilayers, and exhibits a Young's modulus similar to in vivo values for liver tissue. Only the 3D liver models simultaneously maintain hepatic phenotype and elicit proliferation, while achieving cellular ratios found in vivo. The nanoscale detachable polymeric interfaces can be modulated to mimic basement membranes that exhibit a wide range of physical properties. This facile approach offers a versatile new avenue in the assembly of engineered tissues. These results demonstrate the ability of the tri-cellular 3D cultures to serve as an organotypic hepatic model that elicits proliferation and maintenance of phenotype and in vivo-like cellular ratios.
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