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Main Title: Bioprinting Perfusion-Enabled Liver Equivalents for Advanced Organ-on-a-Chip Applications
Author(s): Grix, Tobias
Ruppelt, Alicia
Thomas, Alexander
Amler, Anna-Klara
Noichl, Benjamin P.
Lauster, Roland
Kloke, Lutz
Type: Article
Language Code: en
Abstract: 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 P450 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.
Issue Date: 22-Mar-2018
Date Available: 8-Aug-2019
DDC Class: 570 Biowissenschaften; Biologie
Subject(s): bioprinting
liver equivalent
tissue engineering
3D cell-culture
toxin testing
in vitro testing
drug development
Sponsor/Funder: BMWi, 03EFEBE077, EXIST-Forschungstransfer: Cellbricks Bioprinting
Journal Title: Genes
Publisher: MDPI
Publisher Place: Basel
Volume: 9
Issue: 4
Article Number: 176
Publisher DOI: 10.3390/genes9040176
EISSN: 2073-4425
Appears in Collections:FG Medizinische Biotechnologie » Publications

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