TY - JOUR A1 - Kasten, Annika A1 - Naser, Tamara A1 - Brüllhoff, Kristina A1 - Fiedler, Jörg A1 - Müller, Petra A1 - Möller, Martin A1 - Rychly, Joachim A1 - Groll, Jürgen A1 - Brenner, Rolf E. T1 - Guidance of Mesenchymal Stem Cells on Fibronectin Structured Hydrogel Films JF - PLOS ONE N2 - Designing of implant surfaces using a suitable ligand for cell adhesion to stimulate specific biological responses of stem cells will boost the application of regenerative implants. For example, materials that facilitate rapid and guided migration of stem cells would promote tissue regeneration. When seeded on fibronectin (FN) that was homogeneously immmobilized to NCO-sP(EO-stat-PO), which otherwise prevents protein binding and cell adhesion, human mesenchymal stem cells (MSC) revealed a faster migration, increased spreading and a more rapid organization of different cellular components for cell adhesion on fibronectin than on a glass surface. To further explore, how a structural organization of FN controls the behavior of MSC, adhesive lines of FN with varying width between 10 mu m and 80 mu m and spacings between 5 mu m and 20 mu m that did not allow cell adhesion were generated. In dependance on both line width and gaps, cells formed adjacent cell contacts, were individually organized in lines, or bridged the lines. With decreasing sizes of FN lines, speed and directionality of cell migration increased, which correlated with organization of the actin cytoskeleton, size and shape of the nuclei as well as of focal adhesions. Together, defined FN lines and gaps enabled a fine tuning of the structural organization of cellular components and migration. Microstructured adhesive substrates can mimic the extracellular matrix in vivo and stimulate cellular mechanisms which play a role in tissue regeneration. KW - adhesion dynamics KW - migration KW - coatings KW - force KW - networks KW - traction KW - stress KW - tension KW - focal adhesions KW - tissue morphogenesis Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-114897 VL - 9 IS - 10 ER - TY - JOUR A1 - Hütten, Mareike A1 - Dhanasingh, Anandhan A1 - Hessler, Roland A1 - Stöver, Timo A1 - Esser, Karl-Heinz A1 - Möller, Martin A1 - Lenarz, Thomas A1 - Jolly, Claude A1 - Groll, Jürgen A1 - Scheper, Verena T1 - In Vitro and In Vivo Evaluation of a Hydrogel Reservoir as a Continuous Drug Delivery System for Inner Ear Treatment JF - PLoS ONE N2 - Fibrous tissue growth and loss of residual hearing after cochlear implantation can be reduced by application of the glucocorticoid dexamethasone-21-phosphate-disodium-salt (DEX). To date, sustained delivery of this agent to the cochlea using a number of pharmaceutical technologies has not been entirely successful. In this study we examine a novel way of continuous local drug application into the inner ear using a refillable hydrogel functionalized silicone reservoir. A PEG-based hydrogel made of reactive NCO-sP(EO-stat-PO) prepolymers was evaluated as a drug conveying and delivery system in vitro and in vivo. Encapsulating the free form hydrogel into a silicone tube with a small opening for the drug diffusion resulted in delayed drug release but unaffected diffusion of DEX through the gel compared to the free form hydrogel. Additionally, controlled DEX release over several weeks could be demonstrated using the hydrogel filled reservoir. Using a guinea-pig cochlear trauma model the reservoir delivery of DEX significantly protected residual hearing and reduced fibrosis. As well as being used as a device in its own right or in combination with cochlear implants, the hydrogel-filled reservoir represents a new drug delivery system that feasibly could be replenished with therapeutic agents to provide sustained treatment of the inner ear. KW - gels KW - cochlea KW - silicones KW - deafness KW - inner ear KW - drug delivery KW - inflammation KW - connective tissue Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-119375 VL - 9 IS - 8 ER - TY - JOUR A1 - Simsekyilmaz, Sakine A1 - Liehn, Elisa A. A1 - Weinandy, Stefan A1 - Schreiber, Fabian A1 - Megens, Remco T. A. A1 - Theelen, Wendy A1 - Smeets, Ralf A1 - Jockenhövel, Stefan A1 - Gries, Thomas A1 - Möller, Martin A1 - Klee, Doris A1 - Weber, Christian A1 - Zernecke, Alma T1 - Targeting In-Stent-Stenosis with RGD- and CXCL1-Coated Mini-Stents in Mice JF - PLoS ONE N2 - Atherosclerotic lesions that critically narrow the artery can necessitate an angioplasty and stent implantation. Long-term therapeutic effects, however, are limited by excessive arterial remodeling. We here employed a miniaturized nitinol-stent coated with star-shaped polyethylenglycole (star-PEG), and evaluated its bio-functionalization with RGD and CXCL1 for improving in-stent stenosis after implantation into carotid arteries of mice. Nitinol foils or stents (bare metal) were coated with star-PEG, and bio-functionalized with RGD, or RGD/CXCL1. Cell adhesion to star-PEG-coated nitinol foils was unaltered or reduced, whereas bio-functionalization with RGD but foremost RGD/CXCL1 increased adhesion of early angiogenic outgrowth cells (EOCs) and endothelial cells but not smooth muscle cells when compared with bare metal foils. Stimulation of cells with RGD/CXCL1 furthermore increased the proliferation of EOCs. In vivo, bio-functionalization with RGD/CXCL1 significantly reduced neointima formation and thrombus formation, and increased re-endothelialization in apoE\(^{-/-}\) carotid arteries compared with bare-metal nitinol stents, star-PEG-coated stents, and stents bio-functionalized with RGD only. Bio-functionalization of star-PEG-coated nitinol-stents with RGD/CXCL1 reduced in-stent neointima formation. By supporting the adhesion and proliferation of endothelial progenitor cells, RGD/CXCL1 coating of stents may help to accelerate endothelial repair after stent implantation, and thus may harbor the potential to limit the complication of in-stent restenosis in clinical approaches. KW - carotid arteries KW - polymers KW - stent implantation KW - coatings KW - endothelial cells KW - mice KW - fluorescence microscopy KW - stem cells Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-179745 VL - 11 IS - 5 ER -