The effect of sulfation of alginate hydrogels on the specific binding and controlled release of heparin-binding proteins
The effect of sulfation of alginate hydrogels on the specific binding and controlled release of heparin-binding proteins
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DOI：
10.1016/j.biomaterials.2008.04.025
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发表时间：
2008-08-01
期刊：
影响因子：
14
通讯作者：
Cohen, Smadar
中科院分区：
文献类型：
--
作者：
Freeman, Inbar;Kedem, Alon;Cohen, Smadar
为了模拟肝素结合蛋白对肝素/硫酸乙酰肝素的高亲和力，将非硫酸化的海藻酸钠中的糖醛酸硫酸化，并制备混合海藻酸钠/海藻酸钠-硫酸盐水凝胶。表面等离子体共振分析探讨了13种蛋白质与藻酸盐-硫酸盐的相互作用。其中，10个肝素结合蛋白显示出与藻酸盐硫酸盐和肝素的强结合，但不与藻酸盐结合。与藻酸盐-硫酸盐的平衡结合常数与蛋白质和肝素之间获得的平衡结合常数相当或高一个数量级。只有成纤维细胞生长因子（FGF）显示更高的亲和力肝素比藻酸盐硫酸盐。硫酸化的透明质酸，以及，导致强结合的碱性成纤维细胞生长因子的透明质酸硫酸盐，但不透明质酸。藻酸盐/藻酸盐-硫酸盐的混合水凝胶持续释放碱性FGF，释放速率取决于与水凝胶结合的bFGF的百分比。在体内，bFGF结合藻酸盐/藻酸盐-硫酸盐支架的递送诱导了两倍数量的血管的形成，与当bFGF被递送吸附到基质时相比，并且51%的血管成熟，如通过血管的周细胞覆盖所判断的。因此，我们的研究结果描述了工程的海藻酸钠水凝胶的肝素结合蛋白的空间介绍和控制交付。(C)2008爱思唯尔有限公司保留所有权利。
To mimic the high affinity of heparin-binding proteins to heparin/heparan sulfate, the uronic acids in non-sulfated alginate were sulfated, and hydrogels of mixed alginate/alginate-sulfate were fabricated. Surface plasmon resonance analysis probed the interactions of 13 proteins with alginate-sulfate. Of these, the 10 heparin-binding proteins revealed strong binding to alginate-sulfate and heparin, but not to alginate. The equilibrium binding constants to alginate-sulfate were comparable or one order of magnitude higher than those obtained between the proteins and heparin. Only the fibroblast growth factors (FGFs) revealed higher affinity for heparin than to alginate-sulfate. Sulfation of hyaluronan, as well, resulted in strong binding of basic FGF to hyaluronan-sulfate, but not to hyaluronan. Mixed hydrogels of alginate/alginate-sulfate sustained the release of basic FGF, with the release rate being dependent on the percentage of bFGF bound to the hydrogels. In vivo, the delivery of bFGF bound to alginate/alginate-sulfate scaffolds induced the formation of twice the number of blood vessels compared to when bFGF was delivered adsorbed to the matrix and 51% of the vessels were matured, as judged by pericyte coverage of the vessels. Our results thus describe the engineering of alginate hydrogels for the spatially presentation and controlled delivery of heparin-binding proteins. (C) 2008 Elsevier Ltd. All rights reserved.