Wang Qiujing, Gao Yuyuan, Sun Xinlin, Ji Bin, Cui Xubo, Liu Yaqi, Zheng Tao, Chen Chengwei, Jiang Xiaodan, Zhu Aiping, Quan Daping
Department of Neurosurgery, Zhujiang Hospital, The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Southern Medical University, Guangzhou 510282, Guangdong Province, People's Republic of China.
Biomed Mater. 2014 Aug;9(4):045004. doi: 10.1088/1748-6041/9/4/045004. Epub 2014 Jun 19.
Since the introduction of the detachable coil in endovascular treatment of intracranial aneurysms, the in-hospital mortality rate has been significantly decreased. Recurrence of the aneurysm remains the major drawback of using detachable coils. We prepared a bioactive coil coated with poly(d,l-lactide)-7co-(1,3-trimethylene carbonate) (P(DLLA-co-TMC)), a novel copolymer for controlling the release of vascular endothelial growth factor (VEGF). Platinum coils were prepared by successive coating with cationic P(DLLA-co-TMC) and anionic heparin. Then, recombinant human VEGF-165 (rhVEGF) was immobilized by affinity binding to heparin. The morphological characteristics and sustained in vitro release of rhVEGF were examined using scanning electron microscopy and enzyme-linked immunosorbent assay, respectively. The efficacy of these novel coils modified by P(DLLA-co-TMC)/rhVEGF was tested using a common carotid artery aneurysm model in rats. Experimental aneurysms were embolized with unmodified, P(DLLA-co-TMC)/heparin-coated or P(DLLA-co-TMC)/rhVEGF-coated platinum coils (n = 18). The coils were removed on days 15, 30 and 90 after insertion, and the histological and immunohistochemical analysis of factor VIII was performed to confirm the presence of endothelial cells in the organized area. In addition, the controlled in vivo release of VEGF was confirmed by Western blotting analysis. The release of VEGF tended to increase during the whole period and no burst release was observed. In the group treated with P(DLLA-co-TMC)/rhVEGF-coated platinum coils, clot organization and endothelial cell proliferation were accelerated. The immunohistochemistry study showed that the expression of factor VIII was found in the P(DLLA-co-TMC)/rhVEGF-coated coil group but not in the other two groups. Furthermore, Western blotting analysis confirmed that the major released VEGF in the aneurysm sac was from the P(DLLA-co-TMC)/VEGF-coated coil. P(DLLA-co-TMC)/rhVEGF-coated platinum coils can promote clot organization and endothelial cell proliferation in a rat aneurysm model.
自从可脱卸弹簧圈被引入颅内动脉瘤的血管内治疗以来，院内死亡率已显著降低。动脉瘤复发仍然是使用可脱卸弹簧圈的主要缺点。我们制备了一种涂覆有聚（d，l-丙交酯）-共-（1,3-三亚甲基碳酸酯）（P（DLLA-co-TMC））的生物活性弹簧圈，P（DLLA-co-TMC）是一种用于控制血管内皮生长因子（VEGF）释放的新型共聚物。通过依次涂覆阳离子P（DLLA-co-TMC）和阴离子肝素制备铂弹簧圈。然后，通过与肝素的亲和结合固定重组人VEGF-165（rhVEGF）。分别使用扫描电子显微镜和酶联免疫吸附测定法检查rhVEGF的形态特征和体外持续释放情况。使用大鼠颈总动脉瘤模型测试了这些经P（DLLA-co-TMC）/rhVEGF修饰的新型弹簧圈的疗效。用未修饰的、P（DLLA-co-TMC）/肝素涂覆的或P（DLLA-co-TMC）/rhVEGF涂覆的铂弹簧圈栓塞实验性动脉瘤（n = 18）。在插入后第15、30和90天取出弹簧圈，并进行VIII因子的组织学和免疫组织化学分析，以确认有组织区域中内皮细胞的存在。此外，通过蛋白质印迹分析证实了VEGF在体内的可控释放。在整个期间VEGF的释放趋于增加，未观察到突释。在用P（DLLA-co-TMC）/rhVEGF涂覆的铂弹簧圈治疗的组中，血栓形成组织和内皮细胞增殖加速。免疫组织化学研究表明，在P（DLLA-co-TMC）/rhVEGF涂覆的弹簧圈组中发现了VIII因子的表达，而在其他两组中未发现。此外，蛋白质印迹分析证实动脉瘤囊中主要释放的VEGF来自P（DLLA-co-TMC）/VEGF涂覆的弹簧圈。P（DLLA-co-TMC）/rhVEGF涂覆的铂弹簧圈可促进大鼠动脉瘤模型中的血栓形成组织和内皮细胞增殖。
