Lee Hee Jung, Hong Jong-Kyu, Goo Hyun Chul, Lee Won Kyu, Park Ki Dong, Kim Soo Hyun, Yoo Young Mi, Kim Young Ha
Biomaterials Research Center, Korea Institute of Science and Technology, PO Box 131, Cheongnyang, Seoul 130-650, Korea.
J Biomater Sci Polym Ed. 2002;13(8):939-52. doi: 10.1163/156856202320401979.
Although the technique of coronary stenting has remarkably improved long-term results in recent years, (sub)acute thrombosis and late restenosis still remain problems to be solved. Metallic surfaces were regarded as thrombogenic, due to their positive surface charges, and stenosis resulted from the activation and proliferation of vascular smooth muscle cells (VSMCs). In this study, a unique surface modification method for metallic surfaces was studied using a self-assembled monolayer (SAM) technique. The method included the deposition of thin gold layers, the chemisorption of disulfides containing functional groups, and the subsequent coupling of PEG derivatives or heparin utilizing the functional groups of the disulfides. All the reactions were confirmed by ATR-FTIR and XPS. The surface modified with sulfonated PEG (Au-S-PEG-SO3) or heparinized PEG (Au-S-PEG-Hep) exhibited decreased static contact angles and therefore increased hydrophilicity to a great extent, which resulted from the coupling of PEG and the ionic groups attached. In vitro fibrinogen adsorption and platelet adhesion onto the Au-S-PEG-SO3 or Au-S-PEG-Hep surfaces decreased to a great extent, indicating enhanced blood compatibility. This decreased interaction of the modified surfaces should be attributed to the non-adhesive property of PEG and the synergistic effect of sulfonated PEG. The effect of the surface modification on the adhesion and proliferation of VSMCs was also investigated. The modified Au-S-PEG-SO3 or Au-S-PEG-Hep surfaces also exhibited decreased adhesion of VSMCs, while the deposited gold layer itself was effective. The enhanced blood compatibility and the decreased adhesion of VSMCs on the modified metallic surfaces may help to decrease thrombus formation and suppress restenosis. It would therefore be very useful to apply these modified surfaces to stents for improved functions. A long-term in vivo study using animal models is currently under way.
尽管近年来冠状动脉支架技术显著改善了长期治疗效果，但（亚）急性血栓形成和晚期再狭窄仍是有待解决的问题。金属表面因其带正电荷而被认为具有血栓形成倾向，血管平滑肌细胞（VSMC）的激活和增殖会导致狭窄。在本研究中，采用自组装单分子层（SAM）技术研究了一种独特的金属表面改性方法。该方法包括薄金层的沉积、含官能团二硫化物的化学吸附，以及随后利用二硫化物的官能团偶联聚乙二醇（PEG）衍生物或肝素。所有反应均通过衰减全反射傅里叶变换红外光谱（ATR-FTIR）和X射线光电子能谱（XPS）得到证实。用磺化PEG（Au-S-PEG-SO3）或肝素化PEG（Au-S-PEG-Hep）改性的表面静态接触角减小，因此亲水性大幅增加，这是PEG与附着的离子基团偶联的结果。体外纤维蛋白原在Au-S-PEG-SO3或Au-S-PEG-Hep表面的吸附以及血小板的黏附大幅减少，表明血液相容性增强。改性表面这种相互作用的降低应归因于PEG的非黏附特性以及磺化PEG的协同效应。还研究了表面改性对VSMC黏附和增殖的影响。改性后的Au-S-PEG-SO3或Au-S-PEG-Hep表面VSMC的黏附也减少，而沉积的金层本身就有效果。改性金属表面血液相容性的增强以及VSMC黏附的减少可能有助于减少血栓形成并抑制再狭窄。因此，将这些改性表面应用于支架以改善功能将非常有用。目前正在进行使用动物模型的长期体内研究。
