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Published Online: 23 October 2014

The Stiffness and Structure of Three-Dimensional Printed Hydrogels Direct the Differentiation of Mesenchymal Stromal Cells Toward Adipogenic and Osteogenic Lineages

Publication: Tissue Engineering Part A
Volume 21, Issue Number 3-4


The mechanical and physicochemical effects of three-dimensional (3D) printable hydrogels on cell behavior are paramount features to consider before manufacturing functional tissues. We hypothesize that besides good printability and cytocompatibility of a supporting hydrogel for the manufacture of individual tissues, it is equally essential to consider beforehand the desired tissue (bone, cartilage, fat). In light of its application, the structure and stiffness of printable hydrogel matrices influence cell geometry, which in turn impacts the differentiation fate. Embedded human mesenchymal stromal cells in printable type I collagen- and chitosan–agarose blends were induced to differentiate toward osteoblasts and adipocytes. Hydrogels' printability in air versus submerged printing in perfluorocarbon was evaluated according to the height, diameter, uniformity, and stability of 3D printed vertical cylinders. Bipotent differentiation within hydrogels was assessed histologically (morphology, cellularity), by immunohistochemistry (vimentin, smooth muscle actin), two-photon microscopy (spatial distribution), and real-time polymerase chain reaction (ALP, BGLAP, OPN, RUNX2, COL 1, aP2, PPARγ-2). Agarose and agarose blends revealed the most valid printability properties by generating uniform cylinders with an average height of 4 mm. Osteogenic differentiation was preferably achieved in anisotropic soft collagen-rich substrates, whereas adipogenic differentiation mostly occurred in isotropic stiff agarose-rich matrices. The conjugation of type I collagen to agarose with varying ratios is possibly a suitable bioink for a broad range of 3D printed mesenchymal tissues.

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Information & Authors


Published In

cover image Tissue Engineering Part A
Tissue Engineering Part A
Volume 21Issue Number 3-4February 2015
Pages: 740 - 756
PubMed: 25236338


Published in print: February 2015
Published ahead of print: 27 October 2014
Published online: 23 October 2014
Published ahead of production: 18 September 2014
Accepted: 15 September 2014
Received: 23 April 2014


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Daniela F. Duarte Campos, MSc
Department of Dental Materials and Biomaterials Research, RWTH Aachen University Hospital, Aachen, Germany.
Andreas Blaeser, MSc
Department of Dental Materials and Biomaterials Research, RWTH Aachen University Hospital, Aachen, Germany.
Anne Korsten, PhD
Department of Dental Materials and Biomaterials Research, RWTH Aachen University Hospital, Aachen, Germany.
Sabine Neuss, PhD
Institute for Biomedical Engineering, Biointerface Group, Helmholtz Institute of Biomedical Engineering, RWTH Aachen University Hospital, Aachen, Germany.
Institute of Pathology, RWTH Aachen University Hospital, Aachen, Germany.
Jörg Jäkel, PhD
Institute of Pathology, RWTH Aachen University Hospital, Aachen, Germany.
Michael Vogt, PhD
IZKF Aachen, RWTH Aachen University Hospital, Aachen, Germany.
Horst Fischer, PhD
Department of Dental Materials and Biomaterials Research, RWTH Aachen University Hospital, Aachen, Germany.


Address correspondence to:Daniela F. Duarte Campos, MScDepartment of Dental Materials and Biomaterials ResearchRWTH Aachen University HospitalPauwelsstrasse 30Aachen 52074Germany
E-mail: [email protected]

Disclosure Statement

No competing financial interests exist.

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