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Biocompatible Micron-Scale Silk Fibers Fabricated by Microfluidic Wet Spinning
2021, Lüken, Arne, Geiger, Matthias, Steinbeck, Lea, Joel, Anna-Christin, Lampert, Angelika, Linkhorst, John, Wessling, Matthias
For successful material deployment in tissue engineering, the material itself, its mechanical properties, and the microscopic geometry of the product are of particular interest. While silk is a widely applied protein-based tissue engineering material with strong mechanical properties, the size and shape of artificially spun silk fibers are limited by existing processes. This study adjusts a microfluidic spinneret to manufacture micron-sized wet-spun fibers with three different materials enabling diverse geometries for tissue engineering applications. The spinneret is direct laser written (DLW) inside a microfluidic polydimethylsiloxane (PDMS) chip using two-photon lithography, applying a novel surface treatment that enables a tight print-channel sealing. Alginate, polyacrylonitrile, and silk fibers with diameters down to 1 µm are spun, while the spinneret geometry controls the shape of the silk fiber, and the spinning process tailors the mechanical property. Cell-cultivation experiments affirm bio-compatibility and showcase an interplay between the cell-sized fibers and cells. The presented spinning process pushes the boundaries of fiber fabrication toward smaller diameters and more complex shapes with increased surface-to-volume ratio and will substantially contribute to future tailored tissue engineering materials for healthcare applications. © 2021 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH
Electrically Conductive and 3D-Printable Oxidized Alginate-Gelatin Polypyrrole: PSS Hydrogels for Tissue Engineering
2021, Distler, Thomas, Polley, Christian, Shi, Fukun, Schneidereit, Dominik, Ashton, Mark D., Friedrich, Oliver, Kolb, Jürgen F., Hardy, John G., Detsch, Rainer, Seitz, Hermann, Boccaccini, Aldo R.
Electroactive hydrogels can be used to influence cell response and maturation by electrical stimulation. However, hydrogel formulations which are 3D printable, electroactive, cytocompatible, and allow cell adhesion, remain a challenge in the design of such stimuli-responsive biomaterials for tissue engineering. Here, a combination of pyrrole with a high gelatin-content oxidized alginate-gelatin (ADA-GEL) hydrogel is reported, offering 3D-printability of hydrogel precursors to prepare cytocompatible and electrically conductive hydrogel scaffolds. By oxidation of pyrrole, electroactive polypyrrole:polystyrenesulfonate (PPy:PSS) is synthesized inside the ADA-GEL matrix. The hydrogels are assessed regarding their electrical/mechanical properties, 3D-printability, and cytocompatibility. It is possible to prepare open-porous scaffolds via bioplotting which are electrically conductive and have a higher cell seeding efficiency in scaffold depth in comparison to flat 2D hydrogels, which is confirmed via multiphoton fluorescence microscopy. The formation of an interpenetrating polypyrrole matrix in the hydrogel matrix increases the conductivity and stiffness of the hydrogels, maintaining the capacity of the gels to promote cell adhesion and proliferation. The results demonstrate that a 3D-printable ADA-GEL can be rendered conductive (ADA-GEL-PPy:PSS), and that such hydrogel formulations have promise for cell therapies, in vitro cell culture, and electrical-stimulation assisted tissue engineering. © 2021 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH
Granular Cellulose Nanofibril Hydrogel Scaffolds for 3D Cell Cultivation
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
Impact of Reactive Amphiphilic Copolymers on Mechanical Properties and Cell Responses of Fibrin-Based Hydrogels
2020, Al Enezy-Ulbrich, Miriam Aischa, Malyaran, Hanna, de Lange, Robert Dirk, Labude, Norina, Plum, René, Rütten, Stephan, Terefenko, Nicole, Wein, Svenja, Neuss, Sabine, Pich, Andrij
Mechanical properties of hydrogels can be modified by the variation of structure and concentration of reactive building blocks. One promising biological source for the synthesis of biocompatible hydrogels is fibrinogen. Fibrinogen is a glycoprotein in blood, which can be transformed enzymatically to fibrin playing an important role in wound healing and clot formation. In the present work, it is demonstrated that hybrid hydrogels with their improved mechanical properties, tunable internal structure, and enhanced resistance to degradation can be synthesized by a combination of fibrinogen and reactive amphiphilic copolymers. Water-soluble amphiphilic copolymers with tunable molecular weight and controlled amounts of reactive epoxy side groups are used as reactive crosslinkers to reinforce fibrin hydrogels. In the present work, copolymers that can influence the mechanical properties of fibrin-based hydrogels are used. The reactive copolymers increase the storage modulus of the hydrogels from 600 Pa to 30 kPa. The thickness of fibrin fibers is regulated by the copolymer concentration. It could be demonstrated that the fibrin-based hydrogels are biocompatible and support cell proliferation. Their degradation rate is considerably slower than that of native fibrin gels. In conclusion, fibrin-based hydrogels with tunable elasticity and fiber thickness useful to direct cell responses like proliferation and differentiation are produced. © 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim