本文選題：電化學(xué)沉積 + 界面修飾��； 參考：《吉林大學(xué)》2016年博士論文

【摘要】：冠心病介入治療領(lǐng)域最突出的成就就是經(jīng)皮冠脈介入治療及衍生相關(guān)技術(shù),成功的降低了患者的死亡率。過(guò)去的十年期間,中國(guó)的介入治療在患者例數(shù)方面取得了長(zhǎng)足的進(jìn)步,同時(shí)技術(shù)上日趨成熟,表現(xiàn)為介入相關(guān)總死亡人數(shù)下降,死亡率逐年下降。盡管如此,經(jīng)皮冠脈介入治療本身也不是完美無(wú)缺,自身仍然有尚未解決的缺憾,支架內(nèi)再狹窄及支架內(nèi)血栓形成仍是目前發(fā)生率較高的PCI的并發(fā)癥,盡管發(fā)生機(jī)理較為復(fù)雜,但總體上其發(fā)生與支架平臺(tái)及涂層基質(zhì)及生物活性藥物的相容性及術(shù)中相關(guān)操作等因素有密切關(guān)系,支架材料以及涂層基質(zhì)的疏水性和疏油性能對(duì)支架平臺(tái)的相容性有顯著影響。從目前的研究可知,與316L不銹鋼納米修飾材料相關(guān)的研究數(shù)量不足,尤其是與組織相容性和血液相容性相關(guān)的研究數(shù)量較少,更是缺乏采用改變材料疏水疏油性或者改變316不銹鋼性能對(duì)動(dòng)物實(shí)驗(yàn)相關(guān)研究的報(bào)道。故在316L不銹鋼材料表面沉積銀納米修飾層,對(duì)不銹鋼材質(zhì)的修飾層對(duì)血液和細(xì)胞的相容性進(jìn)行研究和分析,并且制備了316L不銹鋼冠狀動(dòng)脈支架進(jìn)行動(dòng)物實(shí)驗(yàn),檢測(cè)其在動(dòng)物體內(nèi)是否誘導(dǎo)血栓形成及支架內(nèi)再狹窄,為冠狀動(dòng)脈支架表面修飾研究提供依據(jù)。本研究在316L不銹鋼材料表面沉積銀納米修飾層,并經(jīng)全氟硅烷溶液浸泡。掃描電鏡及紅外光譜檢測(cè)均證實(shí)修飾成功,對(duì)顆粒直徑在90-130nm之間的不同電鍍時(shí)間沉積的銀顆粒接觸角進(jìn)行測(cè)試,使之達(dá)到至少130°,疏油角從316L不銹鋼的0°提高到62-72°。按照中華人民共和國(guó)對(duì)醫(yī)療器械的國(guó)家標(biāo)準(zhǔn)GB/T 16886.5-2003要求用蛋白吸附實(shí)驗(yàn)完成生物材料與血漿蛋白的相互作用的評(píng)估;血細(xì)胞與生物材料間的相互作用評(píng)估則通過(guò)溶血性能試驗(yàn)、動(dòng)態(tài)凝血實(shí)驗(yàn)、血小板粘附性能實(shí)驗(yàn)、抗凝血時(shí)間測(cè)定等完成;組織細(xì)胞與生物材料的相容性實(shí)驗(yàn)常常用細(xì)胞毒性試驗(yàn)來(lái)間接評(píng)估。本研究按照要求的相容性指標(biāo)進(jìn)行系列測(cè)試修飾后的316L不銹鋼的血液相容性及細(xì)胞相容性。測(cè)試中發(fā)現(xiàn)白蛋白吸附能力最強(qiáng)者為1600s組,且各組間差異顯著,而各組在吸附纖維蛋白能力上無(wú)顯著差異。而且800s(B)、1600s(C)兩組在抗凝血實(shí)驗(yàn)的各個(gè)時(shí)間節(jié)點(diǎn)總是優(yōu)于裸鋼板組,800s和1600s組的細(xì)胞相容性較好。課題組設(shè)計(jì)的全氟硅烷浸泡的銀鍍膜修飾316L不銹鋼鋼板的最大溶血率僅4.1%,最小溶血率0.4%,均小于5%,符合國(guó)家標(biāo)準(zhǔn)的要求,對(duì)于其大多數(shù)凝血指標(biāo)如凝血酶原時(shí)間,部分凝血活酶時(shí)間、國(guó)際標(biāo)準(zhǔn)化比值、凝血酶原活動(dòng)度,各項(xiàng)指標(biāo)同修飾前并無(wú)太大區(qū)別。電鏡檢測(cè)表明,與裸鋼板相比,各組電沉積銀鍍膜后全氟硅烷浸泡316L不銹鋼板其表面粘附的血小板數(shù)量明顯較少,而且其表面粘附的血小板激活程度也較低。在實(shí)驗(yàn)組各個(gè)沉積時(shí)間不同的鋼板中,沉積時(shí)間為1600秒(B組)的鋼板表面血小板粘附最少,其激活程度也較低,大部分I型。沉積時(shí)間為4000秒(D組)鋼板表面的血小板粘附最多,而且激活程度較高為V型。沉積時(shí)間為800秒(A組)和2000秒(C組)的兩組鋼板表面血小板粘附數(shù)量及激活程度居中。四甲基偶氮唑藍(lán)法(MTT法)檢測(cè)細(xì)胞活性的實(shí)驗(yàn)數(shù)據(jù)表明,隨著培養(yǎng)時(shí)間的增加,各實(shí)驗(yàn)組與對(duì)照組細(xì)胞的數(shù)量增加均顯著,并且兩者的曲線存在很大的相似性,這也充分說(shuō)明了使用全氟硅烷對(duì)實(shí)驗(yàn)組進(jìn)行修飾之后,并未引發(fā)細(xì)胞增殖狀況的顯著變化,并且銀修飾的全氟硅烷鋼板的細(xì)胞相容性更佳。800s和1600s組的銀修飾全氟硅烷鋼板的細(xì)胞相容性較好,但是兩組相比無(wú)明顯的統(tǒng)計(jì)學(xué)意義。流式細(xì)胞儀(Flow Cytometry,FCM)檢測(cè)細(xì)胞周期分布的實(shí)驗(yàn)數(shù)據(jù)表明,處于G期的細(xì)胞,無(wú)論裸鋼板組還是納米銀修飾組均增多,而處于S期和M期的減少,表明實(shí)驗(yàn)組細(xì)胞的DNA合成和有絲分裂被輕度抑制;而各納米銀修飾組的處于G期、S期及M期的細(xì)胞比例與裸鋼板組的相比無(wú)明顯差異(P0.05)。在體試驗(yàn)中,將修飾后的不銹鋼制成冠脈支架,置入靶血管,用血管內(nèi)超聲在宏觀上判斷內(nèi)皮化及再狹窄,對(duì)比病理切片從微觀上評(píng)判試驗(yàn)材料的相關(guān)性能,在體試驗(yàn)顯示,修飾后鋼板制成的支架置入1月后,未增加血栓發(fā)生。組織學(xué)未見明顯的炎癥反應(yīng),各試驗(yàn)組只有800s、2000s、4000s在內(nèi)膜厚度較裸支架薄、內(nèi)膜面積較裸支架小,具有統(tǒng)計(jì)學(xué)意義(p0.05),而1600s組的內(nèi)膜面積與裸支架組無(wú)明顯差異;在中膜厚度、中膜面積指標(biāo)上800s、1600s、2000s組均優(yōu)于裸支架組,具有統(tǒng)計(jì)學(xué)意義(P0.05);在管腔面積方面,800s、1600s、2000s組較裸支架組增大,各組之間無(wú)統(tǒng)計(jì)學(xué)意義。結(jié)論:在316L不銹鋼表面進(jìn)行納米銀進(jìn)行修飾并經(jīng)氟化硅烷浸潤(rùn)后,形成的表面結(jié)構(gòu)改善了接觸角的同時(shí)還具有較好的相容性,并且材料并未觸發(fā)亞急性血栓形成,減少了支架內(nèi)再狹窄的出現(xiàn)。
[Abstract]:The most prominent achievement in the interventional therapy of coronary heart disease is percutaneous coronary intervention and derived related techniques, which have successfully reduced the mortality of the patients. During the past ten years, Chinese interventional therapy has made considerable progress in the number of patients, and the technology is becoming more and more mature, showing a decline in the total number of deaths associated with intervention. The mortality rate is declining year by year. However, percutaneous coronary intervention is not perfect and still has unsolved defects. Stent restenosis and stent thrombosis are still the complications of high incidence of PCI. Although the mechanism is complex, it is generally associated with the scaffolding platform and coating matrix and birth. There is a close relationship between the compatibility of active drugs and the related operations in the operation. The hydrophobicity and oil repellency of the scaffold and the coated matrix have a significant influence on the compatibility of the scaffold. From the present study, the number of studies related to the 316L stainless steel nano modified materials is not enough, especially in the tissue compatibility and blood phase. The number of capacitive related studies is less, and it is lack of reports on the study of animal experiments on changing the hydrophobicity of the materials or changing the properties of 316 stainless steel. Therefore, the silver nano modification layer on the surface of 316L stainless steel is deposited on the surface of stainless steel, and the compatibility of the modified layer of stainless steel to the blood and cell is studied and analyzed. 316L stainless steel coronary stent was used in animal experiments to detect whether the thrombus was induced in the animal and the restenosis in the stent, which provided a basis for the study of the surface modification of the coronary stent. The silver nanoparticles were deposited on the surface of 316L stainless steel and soaked through the perfluorosilane solution. It was proved that the modification was successful. The contact angle of silver particles deposited at different electroplating time between 90-130nm particles was tested to reach at least 130 degrees. The oil repellent angle was raised from 0 degrees of 316L stainless steel to 62-72 degrees. According to the national standard GB/T 16886.5-2003 of People's Republic of China medical equipment, the protein adsorption experiment was required to complete the life. Evaluation of the interaction between material and plasma protein; evaluation of the interaction between blood cells and biomaterials by hemolysis test, dynamic coagulation experiment, platelet adhesion test, anticoagulant time determination, and so on. The compatibility of tissue and biomaterials is often used for indirect evaluation of cytotoxicity test. The blood compatibility and cell compatibility of 316L stainless steel after a series of tests were carried out according to the required compatibility index. The highest albumin adsorption capacity was found in group 1600s, and there were significant differences in each group, but there was no significant difference in the ability to adsorb fibrin. Moreover, 800s (B), 1600s (C) two groups were in anticoagulant experiments. Each time node is always better than the bare plate group. The cell compatibility of the 800s and 1600s groups is better. The maximum hemolysis rate of the 316L stainless steel plate modified by the perfluorsilane immersion coating is only 4.1%, the minimum hemolysis rate is 0.4%, which is less than 5%, which meets the requirements of the national standard, and is suitable for most of the coagulation indexes such as the prothrombin time. There was no significant difference between the thromboplastin time, the international standardization ratio, the prothrombin activity and the prothrombin activity before the modification. The electron microscopic examination showed that the number of platelets adhered to the surface of the 316L stainless steel plate after electrodeposition of silver coated with perfluorosilane was less than that of the bare plate, and the adhesion of the surface of the platelets adhered to the surface of the platelets. In the steel plate with different deposition time in the experimental group, the platelets on the plate surface of 1600 seconds (group B) had the least adherence to the platelets, and the activation degree was lower. Most of the I type. The deposition time was 4000 seconds (group D) on the surface of the platelets, and the degree of activation was higher than that of the V type. The time of deposition was 800 seconds (A group) and 2000 seconds (C). The number and activation of platelets on the two groups of the two groups of plates were in the middle. The experimental data of four methyl azazolium blue (MTT) method to detect cell activity showed that the number of cells increased significantly with the increase of culture time, and there was a great similarity in the curve lines between the two groups. After the modification of fluorosilane, there was no significant change in cell proliferation, and the cytocompatibility of the silver modified perfluorosilane steel plate was better than that of the silver modified perfluorosilane steel plate in.800s and 1600s groups, but there was no significant statistical significance in the two groups. Flow cytometry (Flow Cytometry, FCM) The experimental data of cell cycle distribution showed that the cells in the G stage increased in both the bare plate group and the nano silver modifier, and the decrease in the S phase and the M phase showed that the DNA synthesis and mitosis were slightly inhibited in the experimental group, while the nano silver modifier was in the G phase, the proportion of the cells in the S phase and the M phase with the bare steel plate group. There was no significant difference (P0.05). In the body test, the modified stainless steel was made into a coronary stent, inserted into the target vessel, and judged endothelialization and restenosis with intravascular ultrasound on the macro level. The related properties of the experimental material were judged by the pathological sections. In the body test, the stent made of the modified steel plate was placed in January, without increasing blood. There was no obvious inflammatory reaction in histology. Only 800s, 2000s, 4000s were thinner than bare stents in the endometrium, and the area of the intima was smaller than that of bare scaffold (P0.05), but there was no significant difference between the intima area and the bare stents in the 1600s group. The thickness of the middle membrane and the area index of the middle membrane were superior to those of the naked branch in the group of 800s, 1600s and 2000s. There is statistical significance (P0.05) in the frame group, and in the area of the lumen, the group of 800s, 1600s, and 2000s is larger than the bare scaffold group, and there is no statistical significance between the groups. Conclusion: the surface structure of the 316L stainless steel surface is modified and the surface structure improves the contact angle and has better compatibility, and the material has better compatibility. The material did not trigger subacute thrombosis and reduced the occurrence of in stent restenosis.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R541.4;R318.08

【參考文獻(xiàn)】

相關(guān)期刊論文 前7條

1 吳勃;周明;李保家;王云龍;蔡蘭;;醫(yī)用316L不銹鋼表面微結(jié)構(gòu)的飛秒激光制備及血液相容性研究[J];功能材料;2013年22期

2 杜明珠;姚文軍;宗莉;;抗動(dòng)脈粥樣硬化核酸疫苗納米凍干劑的研究[J];藥學(xué)與臨床研究;2011年02期

3 劉強(qiáng);程曉農(nóng);徐紅星;費(fèi)黃霞;;316L不銹鋼和NiTi合金微磁場(chǎng)表面粗糙度對(duì)血液相容性的影響[J];材料研究學(xué)報(bào);2009年03期

4 湯京龍;奚廷斐;;納米銀生物安全性研究[J];生物醫(yī)學(xué)工程學(xué)雜志;2008年04期

5 鄭黎俊,烏學(xué)東,樓增,吳旦;表面微細(xì)結(jié)構(gòu)制備超疏水表面[J];科學(xué)通報(bào);2004年17期

6 劉敬肖,楊大智,梁成浩,郭亮,孔力,蔡英驥;316L 不銹鋼表面電鍍Rh膜的腐蝕行為及血液相容性研究[J];生物醫(yī)學(xué)工程學(xué)雜志;2001年02期

7 林思聰;高分子生物材料分子工程研究進(jìn)展(上)[J];高分子通報(bào);1997年01期

，

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