Hyaluronan/collagen hydrogel matrices containing high-sulfated hyaluronan microgels for regulating transforming growth f
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Hyaluronan/collagen hydrogel matrices containing high-sulfated hyaluronan microgels for regulating transforming growth factor-β1 Sandra Rother 1 Vera Krönert1 Nicolas Hauck2 Albrecht Berg3 Stephanie Moeller3 Matthias Schnabelrauch3 Julian Thiele2 Dieter Scharnweber1 Vera Hintze1 ●
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Received: 20 March 2019 / Accepted: 10 May 2019 / Published online: 24 May 2019 © Springer Science+Business Media, LLC, part of Springer Nature 2019
Abstract Hyaluronan (HA)-based microgels generated in a microfluidic approach, containing an artificial extracellular matrix composed of collagen and high-sulfated hyaluronan (sHA3), were incorporated into a HA/collagen-based hydrogel matrix. This significantly enhanced the retention of noncrosslinked sHA3 within the gels enabling controlled sHA3 presentation. Gels containing sHA3 bound higher amounts of transforming growth factor-β1 (TGF-β1) compared to pure HA/collagen hydrogels. Moreover, the presence of sHA3-containing microgels improved the TGF-β1 retention within the hydrogels. These findings are promising for developing innovative biomaterials with adjustable sHA3 release and growth factor interaction profiles to foster skin repair, e.g., by rebalancing dysregulated TGF-β1 levels.
Graphical Abstract
1 Introduction Supplementary information The online version of this article (https:// doi.org/10.1007/s10856-019-6267-1) contains supplementary material, which is available to authorized users. * Sandra Rother [email protected] 1
Institute of Materials Science, Max Bergmann Center of Biomaterials, TU Dresden, Budapester Str. 27, 01069 Dresden, Germany
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Institute of Physical Chemistry and Polymer Physics, LeibnizInstitut für Polymerforschung Dresden e.V., 01069 Dresden, Germany
3
Biomaterials Department, INNOVENT e.V., Prüssingstr. 27B, 07745 Jena, Germany
Sulfated glycosaminoglycan (GAG) derivatives positively influence numerous aspects of skin repair [1]. For example, collagen-based artificial extracellular matrices (aECMs) containing high-sulfated hyaluronan (sHA3), named aECM/ sHA3, have been shown to be most efficient in reducing transforming growth factor-β1 (TGF-β1) signaling by binding TGF-β1 to sHA3, thereby blocking receptor recognition [2]. As enhanced TGF-β1 levels stimulate excessive ECM production causing pathological changes like fibrosis [3], sHA3 constitutes a promising component in antifibrosis therapies. While biocompatible hyaluronan (HA)/collagen-based hydrogels containing acrylated, lowsulfated hyaluronan can easily be fabricated [4], sHA3 is
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Journal of Materials Science: Materials in Medicine (2019) 30:65
Fig. 1 Characteristics of microgels and hydrogels. a Chemical structures of HA-AC and sHA3. b Appearance and size distribution of microgels. Microscopic images of stained microgels. sHA3 was visualized by staining with Toluidine blue, and incorporated collagen was stained by Sirius red
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