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Author: Freudenberg, Uwe × Author: Werner, Carsten × DDC: 610 × Type: Text × WGL Institute: IPF ×

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    Poly(2-alkyl-2-oxazoline)-Heparin Hydrogels—Expanding the Physicochemical Parameter Space of Biohybrid Materials
    (Weinheim : Wiley-VCH, 2021) Hahn, Dominik; Sonntag, Jannick M.; Lück, Steffen; Maitz, Manfred F.; Freudenberg, Uwe; Jordan, Rainer; Werner, Carsten
    Poly(ethylene glycol) (PEG)-glycosaminoglycan (GAG) hydrogel networks are established as very versatile biomaterials. Herein, the synthetic gel component of the biohybrid materials is systematically varied by combining different poly(2-alkyl-2-oxazolines) (POx) with heparin applying a Michael-type addition crosslinking scheme: POx of gradated hydrophilicity and temperature-responsiveness provides polymer networks of distinctly different stiffness and swelling. Adjusting the mechanical properties and the GAG concentration of the gels to similar values allows for modulating the release of GAG-binding growth factors (VEGF165 and PDGF-BB) by the choice of the POx and its temperature-dependent conformation. Adsorption of fibronectin, growth of fibroblasts, and bacterial adhesion scale with the hydrophobicity of the gel-incorporated POx. In vitro hemocompatibility tests with freshly drawn human whole blood show advantages of POx-based gels compared to the PEG-based reference materials. Biohybrid POx hydrogels can therefore enable biomedical technologies requiring GAG-based materials with customized and switchable physicochemical characteristics. © 2021 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.
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    GATA3 promotes the neural progenitor state but not neurogenesis in 3D traumatic injury model of primary human cortical astrocytes
    (Lausanne : Frontiers Media, 2019) Celikkaya, Hilal; Cosacak, Mehmet Ilyas; Papadimitriou, Christos; Popova, Stanislava; Bhattarai, Prabesh; Biswas, Srijeeta Nag; Siddiqui, Tohid; Wistorf, Sabrina; Nevado-Alcalde, Isabel; Naumann, Lisa; Mashkaryan, Violeta; Brandt, Kerstin; Freudenberg, Uwe; Werner, Carsten; Kizil, Caghan
    Astrocytes are abundant cell types in the vertebrate central nervous system and can act as neural stem cells in specialized niches where they constitutively generate new neurons. Outside the stem cell niches, however, these glial cells are not neurogenic. Although injuries in the mammalian central nervous system lead to profound proliferation of astrocytes, which cluster at the lesion site to form a gliotic scar, neurogenesis does not take place. Therefore, a plausible regenerative therapeutic option is to coax the endogenous reactive astrocytes to a pre-neurogenic progenitor state and use them as an endogenous reservoir for repair. However, little is known on the mechanisms that promote the neural progenitor state after injuries in humans. Gata3 was previously found to be a mechanism that zebrafish brain uses to injury-dependent induction of neural progenitors. However, the effects of GATA3 in human astrocytes after injury are not known. Therefore, in this report, we investigated how overexpression of GATA3 in primary human astrocytes would affect the neurogenic potential before and after injury in 2D and 3D cultures. We found that primary human astrocytes are unable to induce GATA3 after injury. Lentivirus-mediated overexpression of GATA3 significantly increased the number of GFAP/SOX2 double positive astrocytes and expression of pro-neural factor ASCL1, but failed to induce neurogenesis, suggesting that GATA3 is required for enhancing the neurogenic potential of primary human astrocytes and is not sufficient to induce neurogenesis alone. © 2019 Celikkaya, Cosacak, Papadimitriou, Popova, Bhattarai, Biswas, Siddiqui, Wistorf, Nevado-Alcalde, Naumann, Mashkaryan, Brandt, Freudenberg, Werner and Kizil.