Heparin desulfation modulates VEGF release and angiogenesis in diabetic wounds
Heparin desulfation modulates VEGF release and angiogenesis in diabetic wounds
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DOI：
10.1016/j.jconrel.2015.10.028
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发表时间：
2015-12-28
影响因子：
10.8
通讯作者：
Werner, Carsten
中科院分区：
文献类型：
--
作者：
Freudenberg, Uwe;Zieris, Andrea;Werner, Carsten
虽然血管内皮生长因子（VEGF）已被证明是通过促进血管生成而在伤口愈合中起关键作用的因子之一，但目前该生长因子对伤口环境的临床应用控制不良且不可持续。由硫酸化糖胺聚糖（GAG）制成的水凝胶允许生长因子的持续释放，因为GAG参与生物分子的静电络合。在这里，我们探讨了一组水凝胶形成的选择性取代肝素衍生物和星形聚（乙二醇）相对于VEGF的结合和释放和抗凝活性。作为概念证明，在体外研究了对人脐静脉内皮细胞迁移和管形成的支持作用，并在遗传性糖尿病（db/db）小鼠中研究了促进伤口愈合。我们的数据表明，VEGF从水凝胶的释放依赖于GAG硫酸化模式进行调节。发现具有低硫酸盐含量（初始肝素的11%）的水凝胶在VEGF施用的功效、低抗凝活性和促进血管生成方面是上级的。(C)2015爱思唯尔B. V.保留所有权利。
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.