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    Granular Cellulose Nanofibril Hydrogel Scaffolds for 3D Cell Cultivation
    (Weinheim : Wiley-VCH, 2020) Gehlen, David B.; Jürgens, Niklas; Omidinia-Anarkoli, Abdolrahman; Haraszti, Tamás; George, Julian; Walther, Andreas; Ye, Hua; De Laporte, Laura
    The replacement of diseased and damaged organs remains an challenge in modern medicine. However, through the use of tissue engineering techniques, it may soon be possible to (re)generate tissues and organs using artificial scaffolds. For example, hydrogel networks made from hydrophilic precursor solutions can replicate many properties found in the natural extracellular matrix (ECM) but often lack the dynamic nature of the ECM, as many covalently crosslinked hydrogels possess elastic and static networks with nanoscale pores hindering cell migration without being degradable. To overcome this, macroporous colloidal hydrogels can be prepared to facilitate cell infiltration. Here, an easy method is presented to fabricate granular cellulose nanofibril hydrogel (CNF) scaffolds as porous networks for 3D cell cultivation. CNF is an abundant natural and highly biocompatible material that supports cell adhesion. Granular CNF scaffolds are generated by pre-crosslinking CNF using calcium and subsequently pressing the gel through micrometer-sized nylon meshes. The granular solution is mixed with fibroblasts and crosslinked with cell culture medium. The obtained granular CNF scaffold is significantly softer and enables well-distributed fibroblast growth. This cost-effective material combined with this efficient and facile fabrication technique allows for 3D cell cultivation in an upscalable manner. © 2020 The Authors. Published by Wiley-VCH GmbH
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    Cellulose Nanofibril Hydrogel Promotes Hepatic Differentiation of Human Liver Organoids
    (Weinheim : Wiley-VCH, 2020) Krüger, Melanie; Oosterhoff, Loes A.; van Wolferen, Monique E.; Schiele, Simon A.; Walther, Andreas; Geijsen, Niels; De Laporte, Laura; van der Laan, Luc J.W.; Kock, Linda M.; Spee, Bart
    To replicate functional liver tissue in vitro for drug testing or transplantation, 3D tissue engineering requires representative cell models as well as scaffolds that not only promote tissue production but also are applicable in a clinical setting. Recently, adult liver-derived liver organoids are found to be of much interest due to their genetic stability, expansion potential, and ability to differentiate toward a hepatocyte-like fate. The current standard for culturing these organoids is a basement membrane hydrogel like Matrigel (MG), which is derived from murine tumor material and apart from its variability and high costs, possesses an undefined composition and is therefore not clinically applicable. Here, a cellulose nanofibril (CNF) hydrogel is investigated with regard to its potential to serve as an alternative clinical grade scaffold to differentiate liver organoids. The results show that its mechanical properties are suitable for differentiation with overall, either equal or improved, functionality of the hepatocyte-like cells compared to MG. Therefore, and because of its defined and tunable chemical definition, the CNF hydrogel presents a viable alternative to MG for liver tissue engineering with the option for clinical use. © 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim