Division of Vascular Surgery, Department of Surgery, VA Puget Sound Health Care System, University of Washington School of Medicine, Seattle, Washington, USA.
J Biomed Mater Res A. 2010 Nov;95(2):641-8. doi: 10.1002/jbm.a.32871.
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 ingrowth in vivo into 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.
基于我们对血管内皮生长因子（VEGF）和纤维连接蛋白（FN）基质蛋白特定结构域之间独特协同相互作用的发现，我们使用重组技术构建了一种新型蛋白，这种蛋白来源于 FN 的细胞结合结构域和 VEGF 结合结构域。我们希望验证这样一个假说，即这种原型重组 FN（rFN）蛋白将增强细胞和毛细血管向膨胀聚四氟乙烯（ePTFE）植入物中的体内植入。高孔隙率（60 微米节段间距）的 ePTFE 圆盘用纤维蛋白凝胶和肝素包埋，有/没有 VEGF 和 rFN 的混合物，并植入大鼠的皮下。单独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））的细胞植入。添加 VEGF 或 rFN 均可适度但显著增加细胞植入（分别为 12.7 ± 1%和 11.8 ± 0.98%，p < 0.004）。然而，rFN/VEGF/肝素的组合使细胞植入显著增加（27.6 ± 1.62%，p < 0.001），与所有其他治疗方法相比。毛细血管植入的定量分析得出了相同的模式。这些结果表明，将此类生物调节剂纳入心血管植入物中可能为设计具有增强的血管生成和内皮化能力的即用型小直径假体提供新策略。
