College of Chemistry, Chemical Engineering and Materials Science, Soochow University, 199 Renai Rd., Suzhou 215123, Jiangsu, PR China.
Acta Biomater. 2011 Mar;7(3):954-8. doi: 10.1016/j.actbio.2010.10.021. Epub 2010 Oct 25.
We have developed a potentially fibrinolytic surface in which a bioinert polymer is used as a spacer to immobilize lysine such that the ε-amino group is free to capture plasminogen when in contact with blood. Adsorbed plasminogen can be activated to plasmin and potentially dissolve nascent clots formed on the surface. In previous work lysine was immobilized through a poly(ethylene glycol) (PEG) spacer; however, the graft density of PEG was limited and the resulting adsorbed quantity of plasminogen was insufficient to dissolve clots efficiently. The aim of the present work was to optimize the surface using graft-polymerized poly(2-hydroxyethyl methacrylate) (poly(HEMA)) as a spacer to increase the grafting density of lysine. Such a poly(HEMA)-lysine modified polyurethane (PU) surface is expected to have increased plasminogen binding capacity and clot lysing efficiency compared with PEG-lysine modified PU. A lysine density of 2.81 nmol cm(-2) was measured on the PU-poly(HEMA)-Lys surface vs. 0.76 nmol cm(-2) on a comparable PU-PEG-Lys surface reported previously. The poly(HEMA)-lysine-modified surface was shown to reduce non-specific (fibrinogen) adsorption while binding plasminogen from plasma with high affinity. With increased plasminogen binding capacity these surfaces showed more rapid clot lysis (20 min) in a standard in vitro assay than the corresponding PEG-lysine system (40 min). The data suggest that poly(HEMA) is superior to PEG when used as a spacer in the immobilization of bioactive molecules at high density. This method of modification may also provide a generic approach for preparing bioactive PU surfaces of high activity and low non-specific adsorption of proteins.
我们开发了一种潜在的纤维蛋白溶酶表面，其中生物惰性聚合物用作间隔物来固定赖氨酸，使得 ε-氨基在与血液接触时可以自由捕获纤溶酶原。吸附的纤溶酶原可以被激活为纤溶酶，并有可能溶解表面上形成的初生血栓。在以前的工作中，赖氨酸通过聚乙二醇（PEG）间隔物固定；然而，PEG 的接枝密度有限，并且吸附的纤溶酶原的量不足以有效溶解血栓。本工作的目的是通过接枝聚合的聚（2-羟乙基甲基丙烯酸酯）（poly（HEMA））作为间隔物来优化表面，以增加赖氨酸的接枝密度。与 PEG-赖氨酸修饰的 PU 相比，这种聚（HEMA）-赖氨酸修饰的聚氨酯（PU）表面预计具有增加的纤溶酶原结合能力和血栓溶解效率。在 PU-poly（HEMA）-Lys 表面上测量到的赖氨酸密度为 2.81 nmol cm(-2)，而之前报道的可比的 PU-PEG-Lys 表面上的赖氨酸密度为 0.76 nmol cm(-2)。聚（HEMA）-赖氨酸修饰表面显示出降低非特异性（纤维蛋白原）吸附的同时，从血浆中高亲和力结合纤溶酶原。随着纤溶酶原结合能力的增加，这些表面在标准的体外测定中显示出比相应的 PEG-赖氨酸系统更快的血栓溶解（20 分钟）。数据表明，聚（HEMA）在高密度固定生物活性分子时优于 PEG 作为间隔物。这种修饰方法还可能为制备高活性和低蛋白非特异性吸附的生物活性 PU 表面提供一种通用方法。
