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Authors
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Nowak, M. ; Freudenberg, U. ; Tsurkan, M. ; Werner, C. ; Levental, K.
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Title
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Modular GAG-matrices to promote mammary epithelial morphogenesis in vitro
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Date
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01.01.2017
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Number
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53071
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Abstract
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Matrix systems used to study complex three-dimensional (3D) cellular processes like mammary epithelial tissue morphogenesis and tumorigenesis ex vivo often require ill-defined biological components, which lead to poor reproducibility and a lack of control over physical parameters. In this study, a well-defined, tunable synthetic biohybrid hydrogel composed of the glycosaminoglycan heparin, star-shaped poly(ethylene glycol) (starPEG), and matrix metalloproteinase- (MMP-) cleavable crosslinkers was applied to dissect the biophysical and biochemical signals promoting human mammary epithelial cell (MEC) morphogenesis. We show that compliant starPEG-heparin matrices promote the development of polarized MEC acini. Both the presence of heparin and MMP-cleavable crosslinks are essential in facilitating MEC morphogenesis without supplementation of exogenous adhesion ligands. In this system, MECs secrete and organize laminin in basement membrane-like assemblies to promote integrin signaling and drive acinar development. Therefore, starPEG-heparin hydrogels provide a versatile platform to study mammary epithelial tissue morphogenesis in a chemically defined and precisely tunable 3D in vitro microenvironment. The system allows investigation of biophysical and biochemical aspects of mammary gland biology and potentially a variety of other organoid culture studies.
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Publisher
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Biomaterials
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Wikidata
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Citation
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Biomaterials 112 (2017) 20-30
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DOI
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https://doi.org/dx.doi.org/
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Tags
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mammary epithelium cell-material interaction organoid morphogenesis heparin biomimetic material
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