TY  - JOUR
A1  - Hauptstein, Julia
A1  - Forster, Leonard
A1  - Nadernezhad, Ali
A1  - Horder, Hannes
A1  - Stahlhut, Philipp
A1  - Groll, Jürgen
A1  - Blunk, Torsten
A1  - Teßmar, Jörg
T1  - Bioink Platform Utilizing Dual-Stage Crosslinking of Hyaluronic Acid Tailored for Chondrogenic Differentiation of Mesenchymal Stromal Cells
JF  - Macromolecular Bioscience
N2  - 3D bioprinting often involves application of highly concentrated polymeric bioinks to enable fabrication of stable cell-hydrogel constructs, although poor cell survival, compromised stem cell differentiation, and an inhomogeneous distribution of newly produced extracellular matrix (ECM) are frequently observed. Therefore, this study presents a bioink platform using a new versatile dual-stage crosslinking approach based on thiolated hyaluronic acid (HA-SH), which not only provides stand-alone 3D printability but also facilitates effective chondrogenic differentiation of mesenchymal stromal cells. A range of HA-SH with different molecular weights is synthesized and crosslinked with acrylated (PEG-diacryl) and allylated (PEG-diallyl) polyethylene glycol in a two-step reaction scheme. The initial Michael addition is used to achieve ink printability, followed by UV-mediated thiol–ene reaction to stabilize the printed bioink for long-term cell culture. Bioinks with high molecular weight HA-SH (>200 kDa) require comparably low polymer content to facilitate bioprinting. This leads to superior quality of cartilaginous constructs which possess a coherent ECM and a strongly increased stiffness of long-term cultured constructs. The dual-stage system may serve as an example to design platforms using two independent crosslinking reactions at one functional group, which allows adjusting printability as well as material and biological properties of bioinks.
KW  - hyaluronic acid
KW  - biofabrication
KW  - chondrogenic differentiation
KW  - dual-stage crosslinking
KW  - extracellular matrix
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-257556
VL  - 22
IS  - 2
ER  - 
TY  - JOUR
A1  - Horder, Hannes
A1  - Guaza Lasheras, Mar
A1  - Grummel, Nadine
A1  - Nadernezhad, Ali
A1  - Herbig, Johannes
A1  - Ergün, Süleyman
A1  - Teßmar, Jörg
A1  - Groll, Jürgen
A1  - Fabry, Ben
A1  - Bauer-Kreisel, Petra
A1  - Blunk, Torsten
T1  - Bioprinting and differentiation of adipose-derived stromal cell spheroids for a 3D breast cancer-adipose tissue model
JF  - Cells
N2  - Biofabrication, including printing technologies, has emerged as a powerful approach to the design of disease models, such as in cancer research. In breast cancer, adipose tissue has been acknowledged as an important part of the tumor microenvironment favoring tumor progression. Therefore, in this study, a 3D-printed breast cancer model for facilitating investigations into cancer cell-adipocyte interaction was developed. First, we focused on the printability of human adipose-derived stromal cell (ASC) spheroids in an extrusion-based bioprinting setup and the adipogenic differentiation within printed spheroids into adipose microtissues. The printing process was optimized in terms of spheroid viability and homogeneous spheroid distribution in a hyaluronic acid-based bioink. Adipogenic differentiation after printing was demonstrated by lipid accumulation, expression of adipogenic marker genes, and an adipogenic ECM profile. Subsequently, a breast cancer cell (MDA-MB-231) compartment was printed onto the adipose tissue constructs. After nine days of co-culture, we observed a cancer cell-induced reduction of the lipid content and a remodeling of the ECM within the adipose tissues, with increased fibronectin, collagen I and collagen VI expression. Together, our data demonstrate that 3D-printed breast cancer-adipose tissue models can recapitulate important aspects of the complex cell–cell and cell–matrix interplay within the tumor-stroma microenvironment
KW  - adipose-derived stromal cells
KW  - adipose tissue
KW  - bioprinting
KW  - breast cancer model
KW  - extracellular matrix
KW  - hyaluronic acid
KW  - spheroids
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236496
VL  - 10
IS  - 4
ER  -