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Bioprinting Perfusion-Enabled Liver Equivalents for Advanced Organ-on-a-Chip Applications
Many tissue models have been developed to mimic liver-specific functions for metabolic and toxin conversion in in vitro assays. Most models represent a 2D environment rather than a complex 3D structure similar to native tissue. To overcome this issue, spheroid cultures have become the gold standard...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5924518/ https://www.ncbi.nlm.nih.gov/pubmed/29565814 http://dx.doi.org/10.3390/genes9040176 |
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author | Grix, Tobias Ruppelt, Alicia Thomas, Alexander Amler, Anna-Klara Noichl, Benjamin P. Lauster, Roland Kloke, Lutz |
author_facet | Grix, Tobias Ruppelt, Alicia Thomas, Alexander Amler, Anna-Klara Noichl, Benjamin P. Lauster, Roland Kloke, Lutz |
author_sort | Grix, Tobias |
collection | PubMed |
description | Many tissue models have been developed to mimic liver-specific functions for metabolic and toxin conversion in in vitro assays. Most models represent a 2D environment rather than a complex 3D structure similar to native tissue. To overcome this issue, spheroid cultures have become the gold standard in tissue engineering. Unfortunately, spheroids are limited in size due to diffusion barriers in their dense structures, limiting nutrient and oxygen supply. Recent developments in bioprinting techniques have enabled us to engineer complex 3D structures with perfusion-enabled channel systems to ensure nutritional supply within larger, densely-populated tissue models. In this study, we present a proof-of-concept for the feasibility of bioprinting a liver organoid by combining HepaRG and human stellate cells in a stereolithographic printing approach, and show basic characterization under static cultivation conditions. Using standard tissue engineering analytics, such as immunohistology and qPCR, we found higher albumin and cytochrome P(450) 3A4 (CYP3A4) expression in bioprinted liver tissues compared to monolayer controls over a two-week cultivation period. In addition, the expression of tight junctions, liver-specific bile transporter multidrug resistance-associated protein 2 (MRP2), and overall metabolism (glucose, lactate, lactate dehydrogenase (LDH)) were found to be stable. Furthermore, we provide evidence for the perfusability of the organoids’ intrinsic channel system. These results motivate new approaches and further development in liver tissue engineering for advanced organ-on-a-chip applications and pharmaceutical developments. |
format | Online Article Text |
id | pubmed-5924518 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-59245182018-05-03 Bioprinting Perfusion-Enabled Liver Equivalents for Advanced Organ-on-a-Chip Applications Grix, Tobias Ruppelt, Alicia Thomas, Alexander Amler, Anna-Klara Noichl, Benjamin P. Lauster, Roland Kloke, Lutz Genes (Basel) Article Many tissue models have been developed to mimic liver-specific functions for metabolic and toxin conversion in in vitro assays. Most models represent a 2D environment rather than a complex 3D structure similar to native tissue. To overcome this issue, spheroid cultures have become the gold standard in tissue engineering. Unfortunately, spheroids are limited in size due to diffusion barriers in their dense structures, limiting nutrient and oxygen supply. Recent developments in bioprinting techniques have enabled us to engineer complex 3D structures with perfusion-enabled channel systems to ensure nutritional supply within larger, densely-populated tissue models. In this study, we present a proof-of-concept for the feasibility of bioprinting a liver organoid by combining HepaRG and human stellate cells in a stereolithographic printing approach, and show basic characterization under static cultivation conditions. Using standard tissue engineering analytics, such as immunohistology and qPCR, we found higher albumin and cytochrome P(450) 3A4 (CYP3A4) expression in bioprinted liver tissues compared to monolayer controls over a two-week cultivation period. In addition, the expression of tight junctions, liver-specific bile transporter multidrug resistance-associated protein 2 (MRP2), and overall metabolism (glucose, lactate, lactate dehydrogenase (LDH)) were found to be stable. Furthermore, we provide evidence for the perfusability of the organoids’ intrinsic channel system. These results motivate new approaches and further development in liver tissue engineering for advanced organ-on-a-chip applications and pharmaceutical developments. MDPI 2018-03-22 /pmc/articles/PMC5924518/ /pubmed/29565814 http://dx.doi.org/10.3390/genes9040176 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Grix, Tobias Ruppelt, Alicia Thomas, Alexander Amler, Anna-Klara Noichl, Benjamin P. Lauster, Roland Kloke, Lutz Bioprinting Perfusion-Enabled Liver Equivalents for Advanced Organ-on-a-Chip Applications |
title | Bioprinting Perfusion-Enabled Liver Equivalents for Advanced Organ-on-a-Chip Applications |
title_full | Bioprinting Perfusion-Enabled Liver Equivalents for Advanced Organ-on-a-Chip Applications |
title_fullStr | Bioprinting Perfusion-Enabled Liver Equivalents for Advanced Organ-on-a-Chip Applications |
title_full_unstemmed | Bioprinting Perfusion-Enabled Liver Equivalents for Advanced Organ-on-a-Chip Applications |
title_short | Bioprinting Perfusion-Enabled Liver Equivalents for Advanced Organ-on-a-Chip Applications |
title_sort | bioprinting perfusion-enabled liver equivalents for advanced organ-on-a-chip applications |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5924518/ https://www.ncbi.nlm.nih.gov/pubmed/29565814 http://dx.doi.org/10.3390/genes9040176 |
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