RGD - Functionalized polymer brushes as substrates for the integrin specific adhesion of human umbilical vein endothelial cells
RGD - Functionalized polymer brushes as substrates for the integrin specific adhesion of human umbilical vein endothelial cells
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DOI：
10.1016/j.biomaterials.2007.02.006
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发表时间：
2007-06-01
期刊：
影响因子：
14
通讯作者：
Klok, Harm-Anton
中科院分区：
文献类型：
--
作者：
Tugulu, Stefano;Silacci, Paolo;Klok, Harm-Anton
本报告证明了表面引发原子转移自由基聚合制备薄聚合物层（“刷子”）的可行性，这种聚合物层可以用短肽配体功能化，并且可以用作涂层来促进血液接触生物材料的内皮化。刷子由聚（2-羟乙基甲基丙烯酸酯）（PHEMA）或聚（聚乙二醇）甲基丙烯酸酯)（PPEGMA）组成，它们不仅抑制蛋白质和细胞的非特异性粘附，而且还含有羟基，可用于引入小肽配体。已经开发出一种方案，允许使用含有肽配体的RGD对刷进行功能化，从而使表面浓度范围从0.5-12 pmol/cm(2)。在肽表面浓度为> -5.3 pmol/cm(2)时，发现人脐血管内皮细胞（HUVECs）粘附并迅速扩散。观察了固定在PHEMA和PPEGMA刷上的HUVECs黏附灶的大小和形态差异。这可能是由于PPEGMA刷的乙二醇间隔长度和亲水性增加，这可能导致配体迁移性增加和配体-整合素亲和力降低。固定在聚合物刷上的HUVECs也被发现在暴露于模拟动脉血流的剪切应力时能够保持体内平衡。(c) 2007 Elsevier Ltd.版权所有。
This report demonstrates the feasibility of surface-initiated atom transfer radical polymerization to prepare thin polymer layers ("brushes") that can be functionalized with short peptide ligands and which may be of use as coatings to promote endothelialization of blood-contacting biomaterials. The brushes are composed of poly(2-hydroxyethyl methacrylate) (PHEMA) or poly(poly(ethylene glycol) methacrylate) (PPEGMA), which do not only suppress non-specific adhesion of proteins and cells but also contain hydroxyl groups that can be used to introduce small peptide ligands. A protocol has been developed that allows functionalization of the brushes with RGD containing peptide ligands resulting in surface concentrations ranging from similar to 0.5-12 pmol/cm(2). At peptide surface concentrations > 1-5.3 pmol/cm(2), human umbilical vascular endothelial cells (HUVECs) were found to adhere and spread rapidly. A difference in size and morphology of focal adhesions between HUVECs immobilized on PHEMA and PPEGMA brushes was observed. It is proposed that this is due to the increased ethylene glycol spacer length and hydrophilicity of the PPEGMA brushes, which may lead to increased ligand mobility and reduced ligand-integrin affinity. HUVECs immobilized on the polymer brushes were also found to be able to retain homeostasis when exposed to shear stresses that simulated arterial blood flow. (c) 2007 Elsevier Ltd. All rights reserved.