Heparin desulfation modulates VEGF release and angiogenesis in diabetic wounds
| Autor: | Sabine A. Eming, Carsten Werner, Kandice R. Levental, Karolina Chwalek, Manfred F. Maitz, Mikhail V. Tsurkan, Passant Atallah, Andrea Zieris, Uwe Freudenberg |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A Angiogenesis medicine.medical_treatment Neovascularization Physiologic Pharmaceutical Science Pharmacology Diabetes Complications Mice chemistry.chemical_compound Diabetes Mellitus medicine Animals Humans Cells Cultured Glycosaminoglycans Tube formation Wound Healing Heparin Sulfates Growth factor Hydrogels Vascular endothelial growth factor Vascular endothelial growth factor A chemistry Self-healing hydrogels Immunology Wound healing medicine.drug |
| Zdroj: | Journal of Controlled Release. 220:79-88 |
| ISSN: | 0168-3659 |
| DOI: | 10.1016/j.jconrel.2015.10.028 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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