Bioprinting Perfusion-Enabled Liver Equivalents for Advanced Organ-on-a-Chip Applications

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dc.contributor.authorGrix, Tobias
dc.contributor.authorRuppelt, Alicia
dc.contributor.authorThomas, Alexander
dc.contributor.authorAmler, Anna-Klara
dc.contributor.authorNoichl, Benjamin P.
dc.contributor.authorLauster, Roland
dc.contributor.authorKloke, Lutz
dc.date.accessioned2019-08-08T15:26:39Z
dc.date.available2019-08-08T15:26:39Z
dc.date.issued2018-03-22
dc.date.updated2019-08-01T14:56:19Z
dc.description.abstractMany 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.en
dc.description.sponsorshipBMWi, 03EFEBE077, EXIST-Forschungstransfer: Cellbricks Bioprintingen
dc.identifier.eissn2073-4425
dc.identifier.urihttps://depositonce.tu-berlin.de/handle/11303/9731
dc.identifier.urihttp://dx.doi.org/10.14279/depositonce-8764
dc.language.isoenen
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subject.ddc570 Biowissenschaften; Biologiede
dc.subject.otherbioprintingen
dc.subject.otherstereolithographyen
dc.subject.otherliver equivalenten
dc.subject.othertissue engineeringen
dc.subject.otherbioinken
dc.subject.other3D cell-cultureen
dc.subject.othertoxin testingen
dc.subject.otherin vitro testingen
dc.subject.otherdrug developmenten
dc.titleBioprinting Perfusion-Enabled Liver Equivalents for Advanced Organ-on-a-Chip Applicationsen
dc.typeArticleen
dc.type.versionpublishedVersionen
dcterms.bibliographicCitation.articlenumber176en
dcterms.bibliographicCitation.doi10.3390/genes9040176en
dcterms.bibliographicCitation.issue4en
dcterms.bibliographicCitation.journaltitleGenesen
dcterms.bibliographicCitation.originalpublishernameMDPIen
dcterms.bibliographicCitation.originalpublisherplaceBaselen
dcterms.bibliographicCitation.volume9en
tub.accessrights.dnbfreeen
tub.affiliationFak. 3 Prozesswissenschaften::Inst. Biotechnologie::FG Medizinische Biotechnologiede
tub.affiliation.facultyFak. 3 Prozesswissenschaftende
tub.affiliation.groupFG Medizinische Biotechnologiede
tub.affiliation.instituteInst. Biotechnologiede
tub.publisher.universityorinstitutionTechnische Universität Berlinen

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