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Int. J. Mol. Sci. 2018, 19(10), 3129; https://doi.org/10.3390/ijms19103129

Generation of a 3D Liver Model Comprising Human Extracellular Matrix in an Alginate/Gelatin-Based Bioink by Extrusion Bioprinting for Infection and Transduction Studies

1
Institute of Biotechnology, Department of Applied Biochemistry, Technische Universität Berlin, 13355 Berlin, Germany
2
Institute of Chemistry and Biochemistry, Department of Organic Chemistry, Freie Universität Berlin, 14195 Berlin, Germany
3
Berlin-Brandenburger Centrum für Regenerative Therapien, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany
4
Dept. of Internal Medicine/Infectious and Respiratory Diseases, Charité − Universitätsmedizin Berlin, 10117 Berlin, Germany
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 23 August 2018 / Revised: 27 September 2018 / Accepted: 5 October 2018 / Published: 12 October 2018
(This article belongs to the Special Issue Cell-Biomaterial Interaction)
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Abstract

Bioprinting is a novel technology that may help to overcome limitations associated with two-dimensional (2D) cell cultures and animal experiments, as it allows the production of three-dimensional (3D) tissue models composed of human cells. The present study describes the optimization of a bioink composed of alginate, gelatin and human extracellular matrix (hECM) to print human HepaRG liver cells with a pneumatic extrusion printer. The resulting tissue model was tested for its suitability for the study of transduction by an adeno-associated virus (AAV) vector and infection with human adenovirus 5 (hAdV5). We found supplementation of the basic alginate/gelatin bioink with 0.5 and 1 mg/mL hECM provides desirable properties for the printing process, the stability of the printed constructs, and the viability and metabolic functions of the printed HepaRG cells. The tissue models were efficiently transduced by AAV vectors of serotype 6, which successfully silenced an endogenous target (cyclophilin B) by means of RNA interference. Furthermore, the printed 3D model supported efficient adenoviral replication making it suitable to study virus biology and develop new antiviral compounds. We consider the approach described here paradigmatic for the development of 3D tissue models for studies including viral vectors and infectious viruses. View Full-Text
Keywords: adeno-associated virus; adenovirus; bioprinting; infection; transduction; extracellular matrix; liver; organ models; HepaRG; gene silencing adeno-associated virus; adenovirus; bioprinting; infection; transduction; extracellular matrix; liver; organ models; HepaRG; gene silencing
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Hiller, T.; Berg, J.; Elomaa, L.; Röhrs, V.; Ullah, I.; Schaar, K.; Dietrich, A.-C.; Al-Zeer, M.A.; Kurtz, A.; Hocke, A.C.; Hippenstiel, S.; Fechner, H.; Weinhart, M.; Kurreck, J. Generation of a 3D Liver Model Comprising Human Extracellular Matrix in an Alginate/Gelatin-Based Bioink by Extrusion Bioprinting for Infection and Transduction Studies. Int. J. Mol. Sci. 2018, 19, 3129.

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