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Author: Werner, Carsten × Author: Zimmermann, Ralf × End date: 2024 × Start date: 2020 × WGL Institute: IPF ×

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    Cell-Instructive Multiphasic Gel-in-Gel Materials
    (Weinheim : Wiley-VCH, 2020) Kühn, Sebastian; Sievers, Jana; Stoppa, Aukha; Träber, Nicole; Zimmermann, Ralf; Welzel, Petra B.; Werner, Carsten
    Developing tissue is typically soft, highly hydrated, dynamic, and increasingly heterogeneous matter. Recapitulating such characteristics in engineered cell-instructive materials holds the promise of maximizing the options to direct tissue formation. Accordingly, progress in the design of multiphasic hydrogel materials is expected to expand the therapeutic capabilities of tissue engineering approaches and the relevance of human 3D in vitro tissue and disease models. Recently pioneered methodologies allow for the creation of multiphasic hydrogel systems suitable to template and guide the dynamic formation of tissue- and organ-specific structures across scales, in vitro and in vivo. The related approaches include the assembly of distinct gel phases, the embedding of gels in other gel materials and the patterning of preformed gel materials. Herein, the capabilities and limitations of the respective methods are summarized and discussed and their potential is highlighted with some selected examples of the recent literature. As the modularity of the related methodologies facilitates combinatorial and individualized solutions, it is envisioned that multiphasic gel-in-gel materials will become a versatile morphogenetic toolbox expanding the scope and the power of bioengineering technologies. © 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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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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    Non-leaching, Highly Biocompatible Nanocellulose Surfaces That Efficiently Resist Fouling by Bacteria in an Artificial Dermis Model
    (Washington, DC : ACS Publications, 2020) Hassan, Ghada; Forsman, Nina; Wan, Xing; Keurulainen, Leena; Bimbo, Luis M.; Stehl, Susanne; van Charante, Frits; Chrubasik, Michael; Prakash, Aruna S.; Johansson, Leena-Sisko; Mullen, Declan C.; Johnston, Blair F.; Zimmermann, Ralf; Werner, Carsten; Yli-Kauhaluoma, Jari; Coenye, Tom; Saris, Per E.J.; Österberg, Monika; Moreira, Vânia M.
    Bacterial biofilm infections incur massive costs on healthcare systems worldwide. Particularly worrisome are the infections associated with pressure ulcers and prosthetic, plastic, and reconstructive surgeries, where staphylococci are the major biofilm-forming pathogens. Non-leaching antimicrobial surfaces offer great promise for the design of bioactive coatings to be used in medical devices. However, the vast majority are cationic, which brings about undesirable toxicity. To circumvent this issue, we have developed antimicrobial nanocellulose films by direct functionalization of the surface with dehydroabietic acid derivatives. Our conceptually unique design generates non-leaching anionic surfaces that reduce the number of viable staphylococci in suspension, including drug-resistant Staphylococcus aureus, by an impressive 4-5 log units, upon contact. Moreover, the films clearly prevent bacterial colonization of the surface in a model mimicking the physiological environment in chronic wounds. Their activity is not hampered by high protein content, and they nurture fibroblast growth at the surface without causing significant hemolysis. In this work, we have generated nanocellulose films with indisputable antimicrobial activity demonstrated using state-of-the-art models that best depict an "in vivo scenario". Our approach is to use fully renewable polymers and find suitable alternatives to silver and cationic antimicrobials. © 2020 American Chemical Society.