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Fabrication of modular hyaluronan-PEG hydrogels to support 3D cultures of hepatocytes in a perfused liver-on-a-chip device
Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, Faculty of Science & Engineering.ORCID iD: 0000-0001-5914-2837
Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.ORCID iD: 0000-0001-7921-8915
Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.ORCID iD: 0000-0002-2803-2237
Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.ORCID iD: 0000-0002-1781-1489
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2019 (English)In: Biofabrication, ISSN 1758-5082, E-ISSN 1758-5090, Vol. 11, no 1, article id 015013Article in journal (Refereed) Published
Abstract [en]

Liver cell culture models are attractive in both tissue engineering and for development of assays for drug toxicology research. To retain liver specific cell functions, the use of adequate cell types and culture conditions, such as a 3Dorientation of the cells and a proper supply of nutrients and oxygen, are critical. In this article, we show how extracellular matrix mimetic hydrogels can support hepatocyte viability and functionality in a perfused liver-on-a-chip device. A modular hydrogel system based on hyaluronan and poly(ethylene glycol) (HA-PEG), modified with cyclooctyne moieties for bioorthogonal strain-promoted alkyne-azide 1, 3-dipolar cycloaddition (SPAAC), was developed, characterized, and compared for cell compatibility to hydrogels based on agarose and alginate. Hepatoma cells (HepG2) formed spheroids with viable cells in all hydrogels with the highest expression of albumin and urea in alginate hydrogels. By including an excess of cyclooctyne in theHA backbone, azide-modified cell adhesion motifs (linear and cyclicRGDpeptides) could be introduced in order to enhance viability and functionality of human induced pluripotent stem cell derived hepatocytes (hiPS-HEPs). In the HA-PEG hydrogels modified with cyclicRGDpeptides hiPS-HEPs migrated and grew in 3D and showed an increased viability and higher albumin production compared to when cultured in the other hydrogels. This flexible SPAAC crosslinked hydrogel system enabled fabrication of perfused 3D cell culture of hiPS-HEPs and is a promising material for further development and optimization of liver-on-a-chip devices.

Place, publisher, year, edition, pages
Institute of Physics Publishing (IOPP), 2019. Vol. 11, no 1, article id 015013
Keywords [en]
Organ-on-a-chip; biofabrication; bioorthogonal crosslinking; cell-binding motif; microfluidics
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-153971DOI: 10.1088/1758-5090/aaf657ISI: 000454550900002PubMedID: 30523863Scopus ID: 2-s2.0-85059228017OAI: oai:DiVA.org:liu-153971DiVA, id: diva2:1281540
Note

Funding Agencies|EU Innovative Medicines Initiative Joint Undertaking [115439]; European Union; Swedish Research Council (VR) [B0431901]; Swedish Foundation for Strategic Research (SFF) [FFL15-0026]; Carl Trygger Foundation [CTS15:79]; Knut and Alice Wallenberg Foundation [KAW 2016.0231]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University (Faculty Grant SFO-Mat-LiU) [2009-00971]

Available from: 2019-01-22 Created: 2019-01-22 Last updated: 2019-02-01Bibliographically approved

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Christoffersson, JonasAronsson, ChristopherJury, MichaelSelegård, RobertMandenius, Carl-Fredrik

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