Park K, Shim H S, Dewanjee M K, Eigler N L
Purdue University, Department of Pharmaceutics and Biomedical Engineering, West Lafayette, IN 47907, USA.
J Biomater Sci Polym Ed. 2000;11(11):1121-34. doi: 10.1163/156856200744228.
The initial step of thrombus formation on blood-contacting biomaterials is known to be adsorption of blood proteins followed by platelet adhesion. Poly(ethylene oxide) (PEO) has been frequently used to modify biomaterial surfaces to minimize or prevent protein adsorption and cell adhesion. PEO was grafted onto a number of biomaterials in our laboratory. Nitinol stents and glass tubes were grafted with PEO by priming the metal surface with trichlorovinylsilane (TCVS) followed by adsorption of Pluronic and y-irradiation. Nitinol stents were also coated with Carbothane for PEO grafting. Chemically inert polymeric biomaterials, such as Carbothane, polyethylene, silicone rubber, and expanded polytetrafluoroethylene (e-PTFE), were first adsorbed with PEO-polybutadiene-PEO (PEO-PB-PEO) triblock copolymers and then exposed to gamma-irradiation for covalent grafting. For PEO grafting to Dacron (polyethylene terephthalate), the surface was sequentially treated with PEO-PB-PEO and Pluronics followed by gamma-irradiation. In vitro studies showed substantial reduction in fibrinogen adsorption and platelet adhesion to the PEO-grafted surfaces compared with control surfaces. Fibrinogen adsorption was reduced by 70-95% by PEO grafting on all surfaces, except for e-PTFE. The platelet adhesion corresponded to the fibrinogen adsorption. When the PEO-grafted surfaces were tested ex vivo/in vivo, however, the expected beneficial effect of PEO grafting was inconsistent. The beneficial effect of the PEO grafting was most pronounced on the PEO-grafted nitinol stents. Thrombus formation was reduced by more than 85% by PEO grafting on metallic stents. Only moderate improvement (i.e. 35% decrease in platelet deposition) was observed with PEO-grafted tubes of polyethylene, silicone rubber, and glass. For PEO-grafted heart valves made of Dacron, however, no effect of PEO grafting was observed at all. It appears that the extent of thrombus formation on PEO-grafted biomaterials was directly related to the extent of tissue damage during implantation surgery. Platelets can be activated and form aggregates in the bulk blood, and the formed platelet aggregates may be able to deposit on the PEO monolayer overcoming its repulsive property. Our studies indicate that the testing of in vitro platelet adhesion should include adhesion of large platelet aggregates, in addition to adhesion of individual platelets. Furthermore, the surface modification methods should be improved over the current monolayer grafting concept so that the repulsive force by the grafted PEO layers is large enough to prevent adhesion of platelet aggregates formed in the bulk blood before arriving at the biomaterial surface.
众所周知，在与血液接触的生物材料上形成血栓的初始步骤是血液蛋白吸附，随后是血小板黏附。聚环氧乙烷（PEO）经常被用于修饰生物材料表面，以尽量减少或防止蛋白质吸附和细胞黏附。在我们实验室中，PEO被接枝到多种生物材料上。通过用三氯乙烯硅烷（TCVS）处理金属表面，随后吸附普朗尼克并进行γ辐照，将PEO接枝到镍钛诺支架和玻璃管上。镍钛诺支架也涂覆了卡波硫因以进行PEO接枝。首先将化学惰性的聚合物生物材料，如卡波硫因、聚乙烯、硅橡胶和膨体聚四氟乙烯（e-PTFE），用PEO-聚丁二烯-PEO（PEO-PB-PEO）三嵌段共聚物进行吸附，然后进行γ辐照以实现共价接枝。对于将PEO接枝到涤纶（聚对苯二甲酸乙二酯）上，表面依次用PEO-PB-PEO和普朗尼克进行处理，随后进行γ辐照。体外研究表明，与对照表面相比，PEO接枝表面上纤维蛋白原吸附和血小板黏附显著减少。除了e-PTFE之外，在所有表面上通过PEO接枝，纤维蛋白原吸附减少了70 - 95%。血小板黏附与纤维蛋白原吸附相对应。然而，当对PEO接枝表面进行离体/体内测试时，PEO接枝的预期有益效果并不一致。PEO接枝的有益效果在PEO接枝的镍钛诺支架上最为明显。通过在金属支架上进行PEO接枝，血栓形成减少了超过85%。对于PEO接枝的聚乙烯、硅橡胶和玻璃管，仅观察到适度改善（即血小板沉积减少35%）。然而，对于由涤纶制成的PEO接枝心脏瓣膜，根本未观察到PEO接枝的效果。看来在PEO接枝生物材料上血栓形成的程度与植入手术期间组织损伤的程度直接相关。血小板可在全血中被激活并形成聚集体，并且形成的血小板聚集体可能能够沉积在PEO单分子层上，克服其排斥特性。我们的研究表明，体外血小板黏附测试除了单个血小板的黏附之外，还应包括大血小板聚集体的黏附。此外，表面改性方法应在当前单分子层接枝概念的基础上加以改进，以使接枝的PEO层产生的排斥力足够大，以防止在到达生物材料表面之前在全血中形成的血小板聚集体的黏附。
