Alibeik Sara, Zhu Shiping, Yau Jonathan W, Weitz Jeffrey I, Brash John L
a School of Biomedical Engineering, McMaster University , 1280 Main Street West , Hamilton , ON , Canada , L8S 4K1.
J Biomater Sci Polym Ed. 2012;23(15):1981-93. doi: 10.1163/092050611X603250. Epub 2012 May 8.
In previous work using gold as a model substrate, we showed that modification of surfaces with poly(ethylene glycol) (PEG) and corn trypsin inhibitor (CTI) rendered them protein resistant and inhibitory against activated factor XII. Sequential attachment of PEG followed by CTI gave superior performance compared to direct attachment of a preformed PEG-CTI conjugate. In the present work, a sequential method was used to attach PEG and CTI to a polyurethane (PU) substrate to develop a material with applicability for blood-contacting medical devices. Controls included surfaces modified only with PEG and only with CTI. Surfaces were characterized by water contact angle and X-ray photoelectron spectroscopy. The surface density of CTI was in the range of a monolayer and was higher on the PU substrate than on gold reported previously. Biointeractions were investigated by measuring fibrinogen adsorption from buffer and plasma, factor XIIa inhibition and plasma clotting time. Both the PU-PEG surfaces and the PU-PEG-CTI surfaces showed low fibrinogen adsorption from buffer and plasma, indicating that PEG retained its protein resistance when conjugated to CTI. Although the CTI density was lower on PU-PEG-CTI than on PU modified only with CTI, PU-PEG-CTI exhibited greater factor XIIa inhibition and a longer plasma clotting time, suggesting that PEG facilitates the interaction of CTI with factor XIIa. Thus sequential attachment of PEG and CTI may be a useful approach to improve the thromboresistance of PU surfaces.
在之前以金为模型基底的工作中，我们表明用聚乙二醇（PEG）和玉米胰蛋白酶抑制剂（CTI）对表面进行修饰可使其具有抗蛋白质特性，并能抑制活化的因子XII。与直接连接预先形成的PEG-CTI共轭物相比，先连接PEG再连接CTI的顺序连接方式具有更优的性能。在本工作中，采用一种顺序方法将PEG和CTI连接到聚氨酯（PU）基底上，以开发一种适用于血液接触医疗设备的材料。对照包括仅用PEG修饰的表面和仅用CTI修饰的表面。通过水接触角和X射线光电子能谱对表面进行表征。CTI的表面密度处于单层范围内，且在PU基底上比先前报道的在金基底上更高。通过测量缓冲液和血浆中纤维蛋白原的吸附、因子XIIa抑制作用和血浆凝血时间来研究生物相互作用。PU-PEG表面和PU-PEG-CTI表面在缓冲液和血浆中均显示出低纤维蛋白原吸附，这表明PEG与CTI共轭时仍保留其抗蛋白质特性。尽管PU-PEG-CTI上的CTI密度低于仅用CTI修饰的PU，但PU-PEG-CTI表现出更大的因子XIIa抑制作用和更长的血浆凝血时间，这表明PEG促进了CTI与因子XIIa的相互作用。因此，PEG和CTI的顺序连接可能是一种改善PU表面抗血栓性的有用方法。
