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Author: Werner, Carsten × End date: 2024 × Start date: 2020 × DDC: 530 × WGL Institute: IPF ×

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Now showing 1 - 4 of 4
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    Biomaterial based strategies to reconstruct the nigrostriatal pathway in organotypic slice co-cultures
    (Amsterdam [u.a.] : Elsevier, 2021) Ucar, Buket; Kajtez, Janko; Foidl, Bettina M.; Eigel, Dimitri; Werner, Carsten; Long, Katherine R.; Emnéus, Jenny; Bizeau, Joëlle; Lomora, Mihai; Pandit, Abhay; Newland, Ben; Humpel, Christian
    Protection or repair of the nigrostriatal pathway represents a principal disease-modifying therapeutic strategy for Parkinson's disease (PD). Glial cell line-derived neurotrophic factor (GDNF) holds great therapeutic potential for PD, but its efficacious delivery remains difficult. The aim of this study was to evaluate the potential of different biomaterials (hydrogels, microspheres, cryogels and microcontact printed surfaces) for reconstructing the nigrostriatal pathway in organotypic co-culture of ventral mesencephalon and dorsal striatum. The biomaterials (either alone or loaded with GDNF) were locally applied onto the brain co-slices and fiber growth between the co-slices was evaluated after three weeks in culture based on staining for tyrosine hydroxylase (TH). Collagen hydrogels loaded with GDNF slightly promoted the TH+ nerve fiber growth towards the dorsal striatum, while GDNF loaded microspheres embedded within the hydrogels did not provide an improvement. Cryogels alone or loaded with GDNF also enhanced TH+ fiber growth. Lines of GDNF immobilized onto the membrane inserts via microcontact printing also significantly improved TH+ fiber growth. In conclusion, this study shows that various biomaterials and tissue engineering techniques can be employed to regenerate the nigrostriatal pathway in organotypic brain slices. This comparison of techniques highlights the relative merits of different technologies that researchers can use/develop for neuronal regeneration strategies. © 2020
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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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    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