In situ endothelialization of intravascular stents coated with an anti-CD34 antibody functionalized heparin-collagen multilayer
In situ endothelialization of intravascular stents coated with an anti-CD34 antibody functionalized heparin-collagen multilayer
复制标题
涂有抗CD34抗体功能化肝素-胶原多层的血管内支架的原位内皮化
DOI：
10.1016/j.biomaterials.2010.01.092
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发表时间：
2010-05-01
期刊：
影响因子：
14
通讯作者：
Ji, Jian
中科院分区：
文献类型：
--
作者：
Lin, Quankui;Ding, Xin;Ji, Jian
支架内再狭窄(ISR)和晚期支架血栓形成(LAST)是支架置入最常见的失败，两者都是由损伤的内皮细胞介导的。自然的内皮修复机制提供了一种通过刺激邻近内皮细胞(ECs)迁移或直接从血液循环中捕获循环内皮细胞(CEC)来实现植入物原位内皮化的途径。本文通过逐层组装的方法，研制了一种抗CD34抗体功能化的肝素/胶原多层膜。椭偏仪和QCM-D结果表明，具有轻微戊二醛交联度的多层涂层在静态孵化和冲洗条件下分别是稳定的。体外血液相容性试验和细胞培养结果表明，无论有无抗CD34抗体功能化的肝素/胶原多层膜，不仅保持了良好的血液相容性，而且显著促进了细胞的附着和生长。肝素/胶原多层膜对血管内皮细胞和平滑肌细胞无选择性促进作用，而抗CD34抗体功能化的肝素/胶原多层膜可以特异性地促进血管内皮细胞的附着和生长。代谢活性测定和NO分泌测定进一步表明，在抗CD34抗体功能化的肝素/胶原多层膜表面黏附的内皮细胞具有较好的活性，具有天然血管内皮细胞的特异性功能。体内实验表明，抗CD34抗体能丰富和加速血管细胞在支架上的附着，并实现快速内皮化。裸金属支架与肝素/胶原蛋白修饰多层支架的新生内膜增生无明显差异，而抗CD34抗体功能化多层支架的新生内膜增殖明显受到抑制。抗CD34抗体功能化肝素/胶原多层涂层在快速内皮化和抗再狭窄方面的成功可能表明，将ECs特异性配体固定在细胞相容的基质上是一种很好的原位内皮化方法，也是一种可能的解决ISR的方法。(C)2010爱思唯尔有限公司。保留所有权利。
The in-stent restenosis (ISR) and the late stent thrombosis (LAST) represent the most common failures of stent implantation and are both mediated at the injured endothelium. The natural endothelium healing mechanism provides an approach to achieve in situ endothelialization of the implant by stimulating the neighboring endothelial cells (ECs) migration or capturing the circulating endothelial cells (CEC) directly from the blood circulation. An anti-CD34 antibody functionalized multilayer of heparin/collagen is developed here via layer-by-layer assemble. The ellipsometry and QCM-D results demonstrate that the multilayer coatings with slight glutaraldehyde cross-linking are stable in static incubation and flushing conditions, respectively. The in vitro hemocompatibility tests and cell culture results indicate that both heparin/collagen multilayers with or without the anti-CD34 antibody functionalization not only preserve good hemocompatibility, but also promote cell attachment and growth notably. While the heparin/collagen multilayer coatings show no selectivity in promotion of ECs and smooth muscle cells (SMCs), the anti-CD34 antibody functionalized heparin/collagen multilayers can specifically promote the attachment and growth of the vascular ECs. The metabolic activity assessment and the NO secretion measurements further indicate that the adherent ECs on the anti-CD34 antibody functionalized heparin/collagen multilayer surface have better viability and possess the specific function of the natural vascular ECs. In vivo experiments indicate that the anti-CD34 antibody can enrich and accelerate the attachment of the vascular cells onto the stent and rapid endothelialization is realized. While no significant difference of neointimal hyperplasia is observed between the bare metal stents and heparin/collagen multilayer modified stents, the neointimal hyperplasia on the anti-CD34 antibody functionalized multilayer modified stents is significantly inhibited. The success of the anti-CD34 antibody functionalized heparin/collagen multilayer coating in rapid endothelialization and anti-restenosis might indicate that the immobilization of ECs specific ligand onto a cytocompatible matrix can be a good approach for in situ endothelialization and a possible solution to ISR. (C) 2010 Elsevier Ltd. All rights reserved.