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    Pros and Cons : Supramolecular or Macromolecular : What Is Best for Functional Hydrogels with Advanced Properties?
    (Weinheim : Wiley-VCH, 2020) Eelkema, Rienk; Pich, Andrij
    Hydrogels are fascinating soft materials with unique properties. Many biological systems are based on hydrogel-like structures, underlining their versatility and relevance. The properties of hydrogels strongly depend on the structure of the building blocks they are composed of, as well as the nature of interactions between them in the network structure. Herein, gel networks made by supramolecular interactions are compared to covalent macromolecular networks, drawing conclusions about their performance and application as responsive materials. © 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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    Digitally Fabricated and Naturally Augmented In Vitro Tissues
    (Weinheim : Wiley-VCH, 2020) Duarte Campos, Daniela F.; De Laporte, Laura
    Human in vitro tissues are extracorporeal 3D cultures of human cells embedded in biomaterials, commonly hydrogels, which recapitulate the heterogeneous, multiscale, and architectural environment of the human body. Contemporary strategies used in 3D tissue and organ engineering integrate the use of automated digital manufacturing methods, such as 3D printing, bioprinting, and biofabrication. Human tissues and organs, and their intra- and interphysiological interplay, are particularly intricate. For this reason, attentiveness is rising to intersect materials science, medicine, and biology with arts and informatics. This report presents advances in computational modeling of bioink polymerization and its compatibility with bioprinting, the use of digital design and fabrication in the development of fluidic culture devices, and the employment of generative algorithms for modeling the natural and biological augmentation of in vitro tissues. As a future direction, the use of serially linked in vitro tissues as human body-mimicking systems and their application in drug pharmacokinetics and metabolism, disease modeling, and diagnostics are discussed. © 2020 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH
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    Tuning the Local Availability of VEGF within Glycosaminoglycan-Based Hydrogels to Modulate Vascular Endothelial Cell Morphogenesis
    (Weinheim : Wiley-VCH, 2020) Limasale, Yanuar Dwi Putra; Atallah, Passant; Werner, Carsten; Freudenberg, Uwe; Zimmermann, Ralf
    Incorporation of sulfated glycosaminoglycans (GAGs) into cell-instructive polymer networks is shown to be instrumental in controlling the diffusivity and activity of growth factors. However, a subtle balance between local retention and release of the factors is needed to effectively direct cell fate decisions. To quantitatively unravel material characteristics governing these key features, the GAG content and the GAG sulfation pattern of star-shaped poly(ethylene glycol) (starPEG)–GAG hydrogels are herein tuned to control the local availability and bioactivity of GAG-affine vascular endothelial growth factor (VEGF165). Hydrogels containing varying concentrations of heparin or heparin derivatives with different sulfation pattern are prepared and thoroughly characterized for swelling, mechanical properties, and growth factor transport. Mathematical models are developed to predict the local concentration and spatial distribution of free and bound VEGF165 within the gel matrices. The results of simulation and experimental studies concordantly reveal how the GAG concentration and sulfation pattern determine the local availability of VEGF165 within the cell-instructive hydrogels and how the factor—in interplay with cell-instructive gel properties—determines the formation and spatial organization of capillary networks of embedded human vascular endothelial cells. Taken together, this study exemplifies how mathematical modeling and rational hydrogel design can be combined to pave the way for precision tissue engineering. © 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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    Double-Hydrophobic-Coating through Quenching for Hydrogels with Strong Resistance to Both Drying and Swelling
    (Chichester : John Wiley and Sons Ltd, 2020) Mredha, M.T.I.; Le, H.H.; Cui, J.; Jeon, I.
    In recent years, various hydrogels with a wide range of functionalities have been developed. However, owing to the two major drawbacks of hydrogels—air-drying and water-swelling—hydrogels developed thus far have yet to achieve most of their potential applications. Herein, a bioinspired, facile, and versatile method for fabricating hydrogels with high stability in both air and water is reported. This method includes the creation of a bioinspired homogeneous fusion layer of a hydrophobic polymer and oil in the outermost surface layer of the hydrogel via a double-hydrophobic-coating produced through quenching. As a proof-of-concept, this method is applied to a polyacrylamide hydrogel without compromising its mechanical properties. The coated hydrogel exhibits strong resistance to both drying in air and swelling in multiple aqueous environments. Furthermore, the versatility of this method is demonstrated using different types of hydrogels and oils. Because this method is easy to apply and is not dependent on hydrogel surface chemistry, it can significantly broaden the scope of next-generation hydrogels for real-world applications in both wet and dry environments.
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    Impact of Reactive Amphiphilic Copolymers on Mechanical Properties and Cell Responses of Fibrin-Based Hydrogels
    (Weinheim : Wiley-VCH, 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
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    4D Printing of a Light-Driven Soft Actuator with Programmed Printing Density
    (Washington, DC : ACS Publications, 2020) Nishiguchi, Akihiro; Zhang, Hang; Schweizerhof, Sjören; Schulte, Marie Friederike; Mourran, Ahmed; Möller, Martin
    There is a growing interest in the concept of four-dimensional (4D) printing that combines a three-dimensional (3D) manufacturing process with dynamic modulation for bioinspired soft materials exhibiting more complex functionality. However, conventional approaches have drawbacks of low resolution, control of internal micro/nanostructure, and creation of fast, complex actuation due to a lack of high-resolution fabrication technology and suitable photoresist for soft materials. Here, we report an approach of 4D printing that develops a bioinspired soft actuator with a defined 3D geometry and programmed printing density. Multiphoton lithography (MPL) allows for controlling printing density in gels at pixel-by-pixel with a resolution of a few hundreds of nanometers, which tune swelling behaviors of gels in response to external stimuli. We printed a 3D soft actuator composed of thermoresponsive poly(N-isopropylacrylamide) (PNIPAm) and gold nanorods (AuNRs). To improve the resolution of printing, we synthesized a functional, thermoresponsive macrocrosslinker. Through plasmonic heating by AuNRs, nanocomposite-based soft actuators undergo nonequilibrium, programmed, and fast actuation. Light-mediated manufacture and manipulation (MPL and photothermal effect) offer the feasibility of 4D printing toward adaptive bioinspired soft materials. Copyright © 2020 American Chemical Society.
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    Polymer Hydrogels to Guide Organotypic and Organoid Cultures
    (Weinheim : Wiley-VCH, 2020) Magno, Valentina; Meinhardt, Andrea; Werner, Carsten
    Human organotypic and organoid cultures provide increasingly life-like models of tissue/organ development and disease, enable more realistic drug screening, and may ultimately pave the way for new therapies. A broad variety of extracellular matrix-based or inspired materials is instrumental in these approaches. In this review article, the foundations of the related materials design are summarized with an emphasis on the advantages and limitations of decellularized and reconstituted biopolymeric matrices as well as biohybrid and fully synthetic polymer hydrogel systems applied to enable specific organotypic and organoid cultures. Recent progress in the fabrication of defined hydrogel systems offering thoroughly tunable biochemical and biophysical properties is highlighted. Potentialities of hydrogel-based approaches to address the persisting challenges of organoid technologies, namely scalability, connectivity/integration, reproducibility, parallelization, and in situ monitoring are discussed. © 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim