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Hackelbusch S.,Free University of Berlin | Rossow T.,Free University of Berlin | Rossow T.,Helmholtz Center Berlin | Rossow T.,Helmholtz Virtual Institute Multifunctional Materials for Medicine | And 5 more authors.
Advanced Healthcare Materials | Year: 2015

Stimuli-responsive hydrogels are able to change their physical properties such as their elastic moduli in response to changes in their environment. If biocompatible polymers are used to prepare such materials and if living cells are encapsulated within these networks, their switchability allows the cell-matrix interactions to be investigated with unprecedented consistency. In this paper, thermo-responsive macro- and microscopic hydrogels are presented based on azide-functionalized copolymers of poly(N-(2-hydroxypropyl)-methacrylamide) and poly(hydroxyethyl methacrylate) grafted with poly(N-isopropylacrylamide) side chains. Crosslinking of these comb polymers is realized by bio-orthogonal strain-promoted azide-alkyne cycloaddition with cyclooctyne-functionalized poly(ethylene glycol). The resulting hybrid hydrogels exhibit thermo-tunable elasticity tailored by the polymer chain length and grafting density. This bio-orthogonal polymer crosslinking strategy is combined with droplet-based microfluidics to encapsulate living cells into stimuli-responsive microgels, proving them to be a suitable platform for future systematic stem-cell research. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Wischke C.,Helmholtz Center Geesthacht | Wischke C.,Berlin Brandenburg Center for Regenerative Therapies | Wischke C.,Helmholtz Virtual Institute Multifunctional Materials for Medicine | Kruger A.,Helmholtz Center Geesthacht | And 12 more authors.
European Journal of Pharmaceutics and Biopharmaceutics | Year: 2013

Endothelial cells lining the lumen of blood vessels serve as a physiological barrier controlling nanoparticle movement from the vasculature into the tissue. For exploring the effect of polymer hydrophilicity on nanoparticle interactions with human umbilical vein endothelial cells (HUVECs) in vitro, a series of monomodal poly[acrylonitrile-co-(N-vinylpyrrolidone)] model nanoparticles with increasing hydrophilicity as related to their increasing content (0-30 mol.%) of N-vinylpyrrolidone (NVP) were synthesized by miniemulsion polymerization. Nanoparticles with a low NVP content were rapidly endocytized into all cells independent from the particle dose with toxic effects only observed at high particle concentrations, while only 10-30% of the cells incorporated particles with ≥20 mol.% NVP. Since pathologies are often related to inflammation, an inflammatory HUVEC culture condition with IL-1β stimulation has been introduced and suggested to be widely applied for studying nanocarriers, since cellular uptake in this assay was clearly increased for NVP contents ≥20 mol.%. Importantly, the secretion of functional biological mediators by HUVECs was not relevantly influenced by the nanoparticles for both homeostatic and inflammatory conditions. These findings may motivate concepts for nanocarriers specifically targeted to pathologic regions. Additionally, rapidly endocytized Rhodamin B loaded particles with low NVP content may be explored for cell labeling and tracking. © 2013 Elsevier B.V. All rights reserved.

Roch T.,Helmholtz Center Geesthacht | Roch T.,Helmholtz Virtual Institute Multifunctional Materials for Medicine | Kratz K.,Helmholtz Center Geesthacht | Kratz K.,Helmholtz Virtual Institute Multifunctional Materials for Medicine | And 6 more authors.
Clinical Hemorheology and Microcirculation | Year: 2013

Dendritic cells (DC) have a pivotal role during inflammation. DC efficiently present antigens to T cells and shape the subsequent immune response by the secretion of pro- or anti-inflammatory cytokines and by the expression of co-stimulatory molecules. They respond to 'danger signals' such as microbial products or fragments from necrotic cells or tissues, but were also described to be reactive towards biomaterials. However, how mechanical and physical properties of the subjacent substrate influences the DC activation is currently poorly understood. In this study micro patterned inserts prepared from polystyrene (PS) as well as from poly (ether imide) (PEI) with three different roughness levels of i) Rq = 0.29 μm (PS) and 0.23 μm (PEI); ii) Rq = 3.47 μm (PS) and 3.92 μm (PEI); and iii) Rq = 22.16 μm (PS) and 22.65 μm (PEI) were analyzed for their capacity to influence the activation of human monocytes derived DC. Since the DC were directly cultured in the inserts, the effects of the testing material alone could be investigated and influences from additional culture dish material could be excluded. The viability, the expression of the DC activation markers, and their cytokine/chemokine secretion were determined after the incubation with the different inserts in vitro. Both the PS and the PEI inserts did not influence the survival of the DC and their expression of co-stimulatory molecules. The expression of inflammatory cytokines was not altered by the PEI and PS inserts. However, the secretion of chemokines such as CCL2, CCL3, and CCL4 was influenced by the different roughness levels, indicating that material roughness has the capacity to modulate the DC phenotype. The data presented here will help to understand the interaction of DC with structured polymer surfaces. Biomaterial-induced immuno-modulatory effects mediated by DC may promote tissue regeneration or could potentially reduce inflammation caused by the implant material. © 2013 - IOS Press and the authors. All rights reserved.

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