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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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2018 (English)In: Biofabrication, ISSN 1758-5082, E-ISSN 1758-5090, Vol. 11, no 1, p. 1-13, 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 3D orientation 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 the HA backbone, azide-modified cell adhesion motifs (linear and cyclic RGD peptides) 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 cyclic RGD peptides 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 (IOP), 2018. Vol. 11, no 1, p. 1-13, article id 015013
National Category
Cell and Molecular Biology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Cell Biology
Identifiers
URN: urn:nbn:se:liu:diva-154008DOI: 10.1088/1758-5090/aaf657OAI: oai:DiVA.org:liu-154008DiVA, id: diva2:1281374
Available from: 2019-01-22 Created: 2019-01-22 Last updated: 2019-01-22Bibliographically approved
In thesis
1. Organs-on-chips for the pharmaceutical development process: design perspectives and implementations
Open this publication in new window or tab >>Organs-on-chips for the pharmaceutical development process: design perspectives and implementations
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Organs-on-chips are dynamic cell culture devices created with the intention to mimic organ function in vitro. Their purpose is to assess the toxicity and efficacy of drugs and, as early as possible in the pharmaceutical development process, predict the outcome of clinical trials. The aim of this thesis is to explain and discuss these cell culture devices from a design perspective and to experimentally exemplify some of the specific functions that characterize organs-on-chips.

The cells in our body reside in complex environments with chemical and mechanical cues that affect their function and purpose. Such a complex environment is difficult to recreate in the laboratory and has therefore been overlooked in favor of more simple models, i.e. static twodimensional (2D) cell cultures. Numerous recent reports have shown cell culture systems that can resemble the cell’s natural habitat and enhance cell functionality and thereby potentially provide results that better reflects animal and human trials. The way these organs-on-chips improve in vitro cell culture assays is to include e.g. a three-dimensional cell architecture (3D), mechanical stimuli, gradients of oxygen or nutrients, or by combining several relevant cell types that affect each other in close proximity.

The research conducted for this thesis shows how cells in 3D spheroids or in 3D hydrogels can be cultured in perfused microbioreactors. Furthermore, a pump based on electroosmosis, and a method for an objective conceptual design process, is introduced to the field of organs-on-chips.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2018. p. 78
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1907
Keywords
Organs-on-chips, cell culture models, pharmaceutical development, microfluidics
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-145300 (URN)10.3384/diss.diva-145300 (DOI)9789176853597 (ISBN)
Public defence
2018-03-23, Planck, Fysikhuset, Campus Valla, Linköping, 13:30 (English)
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Supervisors
Note

I den tryckta versionen är det ena serienamnet felaktigt. I den elektroniska versionen är detta ändrat till korrekt "Linköping Studies in Science and Technology. Dissertations"

Available from: 2018-02-21 Created: 2018-02-21 Last updated: 2019-09-26Bibliographically approved

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Christoffersson, JonasAronsson, ChristopherJury, MichaelSelegård, RobertAili, DanielMandenius, Carl-Fredrik

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Biofabrication
Cell and Molecular BiologyMedical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)Cell Biology

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