Freudenberg, Uwe ORCID: 0000-0002-1359-1095, Zieris, Andrea, Chwalek, Karolina ORCID: 0000-0002-8947-5605, Tsurkan, Mikhail V. ORCID: 0000-0003-4000-3890, Maitz, Manfred F., Atallah, Passant, Levental, Kandice R., Eming, Sabine A. and Werner, Carsten ORCID: 0000-0003-0189-3448 (2015). Heparin desulfation modulates VEGF release and angiogenesis in diabetic wounds. J. Control. Release, 220. S. 79 - 89. AMSTERDAM: ELSEVIER. ISSN 1873-4995

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Abstract

While vascular endothelial growth factor (VEGF) has been shown to be one of the key players in wound healing by promoting angiogenesis current clinical applications of this growth factor to the wound environment are poorly controlled and not sustainable. Hydrogels made of sulfated glycosaminoglycans (GAG) allow for the sustained release of growth factors since GAGs engage in electrostatic complexation of biomolecules. In here, we explore a set of hydrogels formed of selectively desulfated heparin derivatives and star-shaped poly(ethylene glycol) with respect to VEGF binding and release and anticoagulant activity. As a proof of concept, supportive effects on migration and tube formation of human umbilical vein endothelial cells were studied in vitro and the promotion of wound healing was followed in genetically diabetic (db/db) mice. Our data demonstrate that the release of VEGF from the hydrogels is modulated in dependence on the GAG sulfation pattern. Hydrogels with low sulfate content (11% of initial heparin) were found to be superior in efficacy of VEGF administration, low anticoagulant activity and promotion of angiogenesis. (C) 2015 Elsevier B.V. All rights reserved.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Freudenberg, UweUNSPECIFIEDorcid.org/0000-0002-1359-1095UNSPECIFIED
Zieris, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chwalek, KarolinaUNSPECIFIEDorcid.org/0000-0002-8947-5605UNSPECIFIED
Tsurkan, Mikhail V.UNSPECIFIEDorcid.org/0000-0003-4000-3890UNSPECIFIED
Maitz, Manfred F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Atallah, PassantUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Levental, Kandice R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eming, Sabine A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Werner, CarstenUNSPECIFIEDorcid.org/0000-0003-0189-3448UNSPECIFIED
URN: urn:nbn:de:hbz:38-383497
DOI: 10.1016/j.jconrel.2015.10.028
Journal or Publication Title: J. Control. Release
Volume: 220
Page Range: S. 79 - 89
Date: 2015
Publisher: ELSEVIER
Place of Publication: AMSTERDAM
ISSN: 1873-4995
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ENDOTHELIAL GROWTH-FACTOR; DELIVERY; HYDROGEL; ADHESION; BINDING; WATERMultiple languages
Chemistry, Multidisciplinary; Pharmacology & PharmacyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/38349

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