3D bioprinting of hepatocytes: core–shell structured co-cultures with fibroblasts for enhanced functionality

Abstract With the aim of understanding and recapitulating cellular interactions of hepatocytes in their physiological microenvironment and to generate an artificial 3D in vitro model, a co-culture system using 3D extrusion bioprinting was developed. A bioink based on alginate and methylcellulose (al...

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Autores principales:	Rania Taymour, David Kilian, Tilman Ahlfeld, Michael Gelinsky, Anja Lode
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cd1d5e85a52e424b96734a5ac0a13398
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spelling	oai:doaj.org-article:cd1d5e85a52e424b96734a5ac0a133982021-12-02T11:37:18Z3D bioprinting of hepatocytes: core–shell structured co-cultures with fibroblasts for enhanced functionality10.1038/s41598-021-84384-62045-2322https://doaj.org/article/cd1d5e85a52e424b96734a5ac0a133982021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84384-6https://doaj.org/toc/2045-2322Abstract With the aim of understanding and recapitulating cellular interactions of hepatocytes in their physiological microenvironment and to generate an artificial 3D in vitro model, a co-culture system using 3D extrusion bioprinting was developed. A bioink based on alginate and methylcellulose (algMC) was first shown to be suitable for bioprinting of hepatocytes; the addition of Matrigel to algMC enhanced proliferation and morphology of them in monophasic scaffolds. Towards a more complex system that allows studying cellular interactions, we applied core–shell bioprinting to establish tailored 3D co-culture models for hepatocytes. The bioinks were specifically functionalized with natural matrix components (based on human plasma, fibrin or Matrigel) and used to co-print fibroblasts and hepatocytes in a spatially defined, coaxial manner. Fibroblasts acted as supportive cells for co-cultured hepatocytes, stimulating the expression of certain biomarkers of hepatocytes like albumin. Furthermore, matrix functionalization positively influenced both cell types in their respective compartments by enhancing their adhesion, viability, proliferation and function. In conclusion, we established a functional co-culture model with independently tunable compartments for different cell types via core–shell bioprinting. This provides the basis for more complex in vitro models allowing co-cultivation of hepatocytes with other liver-specific cell types to closely resemble the liver microenvironment.Rania TaymourDavid KilianTilman AhlfeldMichael GelinskyAnja LodeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rania Taymour David Kilian Tilman Ahlfeld Michael Gelinsky Anja Lode 3D bioprinting of hepatocytes: core–shell structured co-cultures with fibroblasts for enhanced functionality
description	Abstract With the aim of understanding and recapitulating cellular interactions of hepatocytes in their physiological microenvironment and to generate an artificial 3D in vitro model, a co-culture system using 3D extrusion bioprinting was developed. A bioink based on alginate and methylcellulose (algMC) was first shown to be suitable for bioprinting of hepatocytes; the addition of Matrigel to algMC enhanced proliferation and morphology of them in monophasic scaffolds. Towards a more complex system that allows studying cellular interactions, we applied core–shell bioprinting to establish tailored 3D co-culture models for hepatocytes. The bioinks were specifically functionalized with natural matrix components (based on human plasma, fibrin or Matrigel) and used to co-print fibroblasts and hepatocytes in a spatially defined, coaxial manner. Fibroblasts acted as supportive cells for co-cultured hepatocytes, stimulating the expression of certain biomarkers of hepatocytes like albumin. Furthermore, matrix functionalization positively influenced both cell types in their respective compartments by enhancing their adhesion, viability, proliferation and function. In conclusion, we established a functional co-culture model with independently tunable compartments for different cell types via core–shell bioprinting. This provides the basis for more complex in vitro models allowing co-cultivation of hepatocytes with other liver-specific cell types to closely resemble the liver microenvironment.
format	article
author	Rania Taymour David Kilian Tilman Ahlfeld Michael Gelinsky Anja Lode
author_facet	Rania Taymour David Kilian Tilman Ahlfeld Michael Gelinsky Anja Lode
author_sort	Rania Taymour
title	3D bioprinting of hepatocytes: core–shell structured co-cultures with fibroblasts for enhanced functionality
title_short	3D bioprinting of hepatocytes: core–shell structured co-cultures with fibroblasts for enhanced functionality
title_full	3D bioprinting of hepatocytes: core–shell structured co-cultures with fibroblasts for enhanced functionality
title_fullStr	3D bioprinting of hepatocytes: core–shell structured co-cultures with fibroblasts for enhanced functionality
title_full_unstemmed	3D bioprinting of hepatocytes: core–shell structured co-cultures with fibroblasts for enhanced functionality
title_sort	3d bioprinting of hepatocytes: core–shell structured co-cultures with fibroblasts for enhanced functionality
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/cd1d5e85a52e424b96734a5ac0a13398
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3D bioprinting of hepatocytes: core–shell structured co-cultures with fibroblasts for enhanced functionality

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