Biointeractive polymers and tissue engineered blood vessels
Biointeractive polymers and tissue engineered blood vessels
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DOI：
10.1016/0142-9612(96)85571-2
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发表时间：
1996-02-01
期刊：
影响因子：
14
通讯作者：
Kim, DU
中科院分区：
文献类型：
--
作者：
Greisler, HP;Gosselin, C;Kim, DU
血管干预后内皮细胞（EC）和平滑肌细胞（SMC）增殖的调节对临床疗效至关重要。我们的实验室已经开发出一种方法，用含有生物活性蛋白的悬浮液浸染生物材料，从而在植入后在体外和体内对EC和SMC的生长进行差异调节。我们之前报道过，用含有FGF-1和肝素的纤维蛋白胶（FG）浸泡60亩节间ePTFE移植物，4周后在狗体内发生融合内皮化，EC和SMC增殖短暂增加。在FGF作用下，20周后胸腹植入物的内囊明显变厚（139亩）。为了减少SMC的增殖，我们研究了FGF-1、肝素和凝血酶浓度对体外SMC生长的影响。FG导致DNA合成增加182% （P < 0.001）。FG中的肝素以剂量依赖的方式减弱了这种作用，在500 U ml（-1）时完全抑制FG诱导的生长（与单独FG相比，P < 0.001）。在不加肝素的FG中，FGF-1没有作用，但在一起，FGF-1引起了剂量依赖性的生长增加，而肝素浓度的增加先增加，后减少增殖。FGF-1和肝素在静止的SMCs培养基中也有类似的作用。只有凝血酶浓度> 3.2 U ml（-1）刺激SMC生长，这种刺激被肝素阻断。FGF和肝素对EC的增殖也有协同作用，但对高浓度肝素的EC生长没有抑制作用。因此，可以通过改变FGF：肝素比例来调节内皮细胞相对于SMCs的相对增殖活性。同样的系统可以与其他蛋白质一起使用，以诱导应用蛋白质的其他局部影响或释放该蛋白质后的全身影响。
The regulation of endothelial cell (EC) and smooth muscle cell (SMC) proliferation following vascular interventions is critical to clinical efficacy. Our laboratory has developed a method of impregnating biomaterials with suspensions containing bioactive proteins resulting in the capability of differentially modulating EC and SMC growth in vitro and in vivo following implantation. We have previously reported that 60 mu internodal distance ePTFE grafts impregnated with fibrin glue (FG) containing FGF-1 and heparin develop confluent endothelialization with transiently increased EC and SMC proliferation after 4 weeks in dogs. Thoraco-abdominal implants after 20 weeks were developed significantly thicker (139 mu) inner capsules in response to the FGF. To minimize SMC proliferation we studied the effects of FGF-1, heparin, and thrombin concentrations on SMC growth in vitro. FG caused a 182% increase (P < 0.001) in DNA synthesis. Heparin within FG diminished this effect in a dose-dependant manner, with complete inhibition of FG-induced growth at 500 U ml(-1) (versus FG alone, P < 0.001). FGF-1 within FG without heparin had no effect, but together, FGF-1 caused a dose-dependant growth increase while increasing heparin concentrations initially increased and then decreased proliferation. FGF-1 and heparin in the medium of quiescent SMCs had similar effects. Only thrombin concentrations > 3.2 U ml(-1) stimulated SMC growth and this stimulation was blocked by heparin. A synergism between FGF and heparin on EC proliferation was also found but without EC growth inhibition in response to higher concentrations of heparin. It is thus possible to modulate the relative proliferative activity of ECs versus SMCs by altering the FGF:heparin ratio. This same system may be useful with other proteins to induce other local affects by the applied protein or systemic affects following release of that protein.