Enhancement of capillary and cellular ingrowth in ePTFE implants with a proangiogenic recombinant construct derived from fibronectin.

Enhancement of capillary and cellular ingrowth in ePTFE implants with a proangiogenic recombinant construct derived from fibronectin.
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使用源自纤连蛋白的促血管生成重组结构增强 ePTFE 植入物中的毛细血管和细胞向内生长。

DOI:
10.1002/jbm.a.32871
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发表时间:
2010
期刊:
Journal of biomedical materials research. Part A
影响因子:
--
通讯作者:
Sobel,Michael
Sobel,Michael
中科院分区:
--
文献类型:
--
作者:
Wijelath,Errol;Kohler,TedR;Murray,Jacqueline;Namekata,Mayumi;Yagi,Mayumi;Sobel,Michael

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基于我们发现血管内皮生长因子(VEGF)和基质蛋白纤连蛋白(FN)的特定结构域之间存在独特的协同相互作用,我们使用重组技术创建了一种源自FN细胞结合和VEGF结合结构域的新蛋白质构建体。我们希望测试的假设,这种原型重组FN(rFN)蛋白将增强细胞和毛细血管向内生长到体内膨胀聚四氟乙烯(ePTFE)植入物。用纤维蛋白凝胶和肝素包埋高孔隙率(60微米节间距)的ePTFE盘,有/没有VEGF和rFN的混合物,并皮下植入大鼠中。仅用纤维蛋白胶和肝素包埋的对照植入物显示出平均8.5%(±0.51%标准误差平均值(SEM))的细胞向内生长。VEGF或rFN的添加引起细胞向内生长的适度但显著的增加(分别为12.7 ± 1%和11.8 ± 0.98%,p< 0.004)。然而,与所有其他治疗相比,rFN/VEGF/肝素的组合显着增加了细胞向内生长(27.6 ± 1.62%,p < 0.001)。毛细血管向内生长的定量产生了相同的模式。这些结果表明,将此类生物调节剂掺入心血管植入物中可以为设计具有增强的新血管形成和内皮化能力的现成小直径假体移植物提供新的策略。© 2010 Wiley Periodicals,Inc.生物医学材料研究杂志A部分,2010年。
Based on our discoveries of a unique, synergistic interplay between vascular endothelial growth factor (VEGF) and specific domains of the matrix protein fibronectin (FN), we used recombinant technology to create a new protein construct derived from the cell‐binding and VEGF‐binding domains of FN. We wished to test the hypothesis that this prototype recombinant FN (rFN) protein would enhance cellular and capillary ingrowthin vivointo expanded polytetrafluoroethylene (ePTFE) implants. ePTFE disks of high porosity (60 micron internodal distance) were embedded with fibrin gel and heparin, with/without mixtures of VEGF and rFN and were implanted subcutaneously in rats. Control implants embedded with fibrin glue and heparin alone showed an average of 8.5% (±0.51% standard error mean (SEM)) cellular ingrowth. The addition of either VEGF or rFN caused a modest but significant increase in cellular ingrowth (12.7 ± 1% and 11.8 ± 0.98%, respectively,p< 0.004). However, the combination of rFN/VEGF/heparin dramatically increased cellular ingrowth (27.6 ± 1.62%,p< 0.001), compared with all other treatments. Quantification of capillary ingrowth yielded the same pattern. These results suggest that the incorporation of such biological modulators into cardiovascular implants could offer new strategies for the design of a ready‐made small diameter prosthetic graft with enhanced capacity for neovascularization and endothelialization. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.
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