疏水疏油纳米银镀膜冠状动脉支架的研究

发布时间：2018-09-14 19:38

【摘要】：目的：在316L不锈钢材料表面制备纳米结构，改善316L不锈钢表面疏水、疏油性能，观察银纳米镀层对血液相容性及细胞相容性的影响，并在316L不锈钢冠脉支架表面制备银纳米镀层，利用动物实验探讨其在生物体内抗支架内血栓及支架内再狭窄的能力，为冠状动脉支架表面改性研究提供依据。方法：本研究采用恒电位电沉积的方法在316L不锈钢表面沉积银纳米镀层，并将钢板置于全氟硅烷溶液中浸泡，达到改变钢板表面微观形貌，改善钢板疏水、疏油性能的目的。电镜及红外光谱检测均证实银纳米涂层成功沉积在316L不锈钢表面，且测试疏水角、疏油角和表面银纳米颗粒直径。通过动态凝血实验、抗凝血时间测定、血小板粘附实验、溶血实验、蛋白吸附实验等手段，测试银镀膜全氟硅烷浸泡316L不锈钢的血液相容性。并通过细胞粘附实验、MTT法及流式细胞仪检测细胞周期的方法测试细胞相容性。将银镀膜全氟硅烷浸泡316L不锈钢具有不同疏水疏油性能的冠脉支架置入兔腹主动脉内，通过比较置入时和1个月后的造影及血管内超声结果，并对比病理切片结果，判断体内环境下，纳米结构及疏水疏油性能改变对内皮化、血栓形成及再狭窄的影响。结果：316L不锈钢利用恒电位电沉积法进行表面沉积银纳米镀层，并以全氟硅烷浸泡后，具备了一定的微相粗糙度，并改善了疏水、疏油性能，血液相容性的很多指标较裸钢板明显改善。比如血小板粘附数量、激活程度、白蛋白吸附量，而抗凝血性能、溶血率及纤维蛋白吸附量至少不次于裸钢板。其中，800s和1600s电镀处理组的抗凝血性能及抗血小板吸附激活能力好于2000s及4000s组。细胞粘附试验，各组全氟硅烷浸泡银纳米镀层疏水、疏油性能改善钢板结果明显好于裸钢板，MTT与流式细胞仪检测显示，疏水、疏油性能改善对细胞相容性无明显影响。动物实验部分，疏水疏油性能改善的316L不锈钢制成的支架置入动物体内后较裸支架不增加置入当时及1个月时血栓发生率，支架具有良好的组织相容性，在支架周围组织没有明显的炎症反应，各组全氟硅烷浸泡的纳米银镀膜316L不锈钢支架内膜厚度都较裸支架薄，内膜面积较裸支架小，其中800s，1600s，4000s均有显著统计学意义（P0.05）；而中膜厚度、中膜面积，800s，1600s，，2000s较裸支架薄，具有统计学意义（P0.05）,4000s与裸支架类似；管腔面积方面，各组之间无统计学意义的差别，但是800s，1600s，2000s组较裸支架组增大。结论：在316L不锈钢表面进行银镀膜并在氟化硅烷中浸泡后，可以形成表面纳米结构，可改善316L不锈钢的疏水疏油性能，并具有良好地血液相容性及细胞相容性。银镀膜全氟硅烷浸泡316L不锈钢支架不影响急性或亚急性血栓形成，并可以加速血管内皮化过程，减少支架内再狭窄的发生。
[Abstract]:Objective: to prepare nanostructures on the surface of 316L stainless steel, to improve the hydrophobic and oil-repellent properties of 316L stainless steel, and to observe the effect of silver nano-coating on blood compatibility and cytocompatibility. Silver nano-coating was prepared on the surface of 316L stainless steel coronary stent, and its ability to resist stent thrombosis and stent restenosis in vivo was investigated by animal experiments, which provided the basis for the study of surface modification of coronary stent. Methods: silver nanocrystalline coating was deposited on 316L stainless steel by potentiostatic electrodeposition, and the steel plate was immersed in perfluorosilane solution to change the surface morphology and improve the hydrophobic and oil-repellent properties of steel plate. The silver nano-coating was successfully deposited on the surface of 316L stainless steel by electron microscope and infrared spectroscopy. The hydrophobic angle, oil thinning angle and the diameter of silver nanoparticles on the surface were measured. The blood compatibility of 316L stainless steel immersed in silver coated perfluorosilane was tested by means of dynamic coagulation test, anticoagulant time measurement, platelet adhesion test, hemolysis test and protein adsorption test. Cell compatibility was tested by MTT assay and flow cytometry. Ag-coated perfluorosilane immersion 316L stainless steel coronary stents with different hydrophobic and oil-repellent properties were implanted into the abdominal aorta of rabbits. The results of angiography and intravascular ultrasound were compared at the time of implantation and 1 month later, and the results of pathological sections were compared. The effects of changes of nanostructure and hydrophobicity on endothelialization thrombosis and restenosis were evaluated in vivo. Results the silver nanocrystalline coating was deposited on the surface of W316L stainless steel by potentiostatic electrodeposition. After immersion in perfluorosilane, the microphase roughness was obtained, and the hydrophobic and oil-repellent properties were improved. Many indexes of blood compatibility were improved obviously compared with bare plate. For example, platelet adhesion, activation, albumin adsorption, anticoagulant properties, hemolysis and fibrin adsorption are at least as good as bare plates. The anticoagulant properties and the anti-platelet adsorption and activation ability were better in the electroplating groups of 800s and 1600s than those in the 200s and 400s groups. The results of cell adhesion test showed that the hydrophobicity of silver nano-coating immersed in perfluorosilane in each group was better than that of naked plate by MTT and flow cytometry. The improvement of hydrophobic and oil-repellent properties had no significant effect on the cell compatibility. In the animal experiment, the 316L stainless steel stent with improved hydrophobicity and oil repellency was put into the animal body without increasing the incidence of thrombus at the time of implantation and one month after the stent was implanted, so the stent had good histocompatibility. There was no obvious inflammatory reaction in the tissue around the scaffold. The thickness of 316L stainless steel stent immersed in perfluorosilane was thinner than that of bare stent, and the intimal area was smaller than that of bare stent, among which 800s / 1600s / 4000s was statistically significant (P0.05). However, the thickness of the middle membrane, the area of the middle membrane of 1600s / 2000s was thinner than that of the bare scaffold, which was similar to that of the bare scaffold (P0.05), but there was no significant difference in the lumen area between the groups, but it was larger in the 800s / 1600s / 2000s group than in the bare scaffold group. Conclusion: after silver plating on 316L stainless steel surface and immersion in fluorinated silane, the surface nanostructures can be formed, and the hydrophobic and oil hydrophobic properties of 316L stainless steel can be improved, with good blood compatibility and cytocompatibility. Silver coated perfluorosilane immersion 316L stainless steel stent does not affect acute or subacute thrombosis and can accelerate the process of vascular endothelialization and reduce the incidence of restenosis in the stent.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2013
【分类号】：R318.08

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