【作者】 王海花；

【导师】 谢东；

【作者基本信息】 西南交通大学 ， 凝聚态物理， 2016， 硕士

【摘要】 Ti02纳米晶薄膜材料具有优异的抗凝血性能以及引导内皮细胞生长的能力,成为心血管医疗器械(如人工血管支架或人工心脏瓣膜)表面改性的一种重要候选材料。生物材料进入临床应用除了进行抗凝血性能检测外还需要进行全身毒性、体外细胞毒性等一系列检测和评级工作。与Ti02纳米晶薄膜材料有相同化学成分和晶型结构的Ti02纳米粒子材料细胞毒性已得到证实,并且Ti02纳米粒子的毒性与粒子尺寸、晶型和UV照射等多种因素有关,但是Ti02纳米晶薄膜材料体外细胞毒性和全身毒性的检测及评级研究的相关报道却还很少见。针对Ti02纳米晶薄膜材料的细胞毒性开展检测和评级工作,不仅可以为Ti02纳米晶薄膜用于心血管植入器件的表面改性应用提供实验和理论依据,另一方面也可以丰富纳米材料生物安全性的研究内容,具有重要的理论和实际应用意义。针对以上问题,本文首先综合运用高功率脉冲磁控溅射(HPPMS)、直流磁控溅射(DCMS)及热处理、真空退火等方式探讨制备不同晶粒尺寸、不同晶型的Ti02纳米晶薄膜材料的工艺参数。然后采用国标IS010993-5：1999中的浸体液法对Ti02纳米晶薄膜材料进行体外细胞毒性研究并进行评级,重点研究了晶粒尺寸、晶型结构及浸提时间对Ti02纳米晶薄膜材料体外细胞毒性评级的影响。参考IS010993-5：1999中的直接接触法研究了紫外照射对Ti02纳米晶薄膜体外细胞毒性评级的影响。通过本文的研究得到以下主要结论：1.HPPMS和DCMS制备的Ti02薄膜表面均比较光滑平整,晶粒尺寸相差较大；经管式炉热处理后,薄膜的晶粒尺寸有所增大,但薄膜表面产生大量的气泡和裂纹；在经真空退火,Ti02薄膜则发生氧溢出,薄膜中出现非饱和的Ti-O膜结构；2.晶粒尺寸和晶型结构对Ti02纳米晶薄膜体外细胞毒性评级无影响,本文研究的晶粒尺寸在10～120nm范围,无论是锐钛矿还是金红石型Ti02纳米晶薄膜体外细胞毒性评级都为1级,满足国标IS010993-5：1999对生物材料细胞毒性的要求。3.浸提时间为3天和60天,Ti02纳米晶薄膜的体外细胞毒性评级无差别。表明纳米晶薄膜在生理环境中将是一种结构非常稳定的材料。4.紫外照射对Ti02纳米晶薄膜体外细胞毒性没有影响,但是对Ti02纳米晶薄膜的生物相容性有所提高。更多还原

【Abstract】 TiO2 nanocrystalline thin film material has the ability of excellent anticoagulant capability and guiding the growth of endothelial cells. Thus it becomes important candidate material for the surface modification of cardiovascular medical apparatus and instrμments(e.g. artificial vascular stents or artificial heart valves). Besides the test of anticoagulation property, biological materials should also make a series of testing and rating regarding the systemic toxicity and in vitro cytotoxicity before entering the clinical application.TiO2 nano-particles, with the same chemical composition and crystal structure as TiO2 nanocrystalline thin film materials, have been approved by their toxicity. Besides, the toxicity of TiO2 nano-particles is related to particle size, crystal structure, UV irradiation and other factors. However, few reports were done concerning testing and rating of systemic toxicity and in vitro cytotoxicity of TiO2 nanocrystalline thin film. Therefore, cell toxicity testing and rating of TiO2 nanocrystalline thin film could not only provide experimental and theoretical basis for the surface modification of cardiovascular implantable devices through using TiO2 nanocrystalline thin film, but also can enrich the research content involving in biological safety of nano materials, thus having important theoretical and practical application significance.For above problems, the method of high power pulsed magnetron sputtering (HPPMS), dc magnetron sputtering (DCMS) and heat treatment, vacuum annealing were applied comprehensively in the paper to explore the prepare parameters on TiO2 nanocrystalline thin film materials with different grain sizes and different crystal structures. Next, the leaching solution method in ISO 10993-5:1999 was adopted to test and rate the in vitro cytotoxicity, which mainly focused on the impact of grain size, crystal structure and leaching time on the in vitro cytotoxicity and rating of TiO2 nanocrystalline thin film material. The direct contact method of ISO 10993-5:1999 was transmitted to study the influence of ultraviolet irradiation on the in vitro cytotoxicity and rating of TiO2 nanocrystalline thin film material. Through the research, the following conclusions can be mainly obtained:1. The surface of TiO2 nanocrystalline thin film material prepared by HPPMS and DCMS is smooth, which had significant difference concerning grain sizes; after heat treatment with furnace, the grain size of the thin film was increased slightly, but numerous bubbles and cracks were produced on the thin film surface; and when annealed by vacuum annealing furnace, the oxygen overflowed and unsaturated Ti-O film structure were occurred in TiO2 nanocrystalline film;2.Grain size and crystal structure had no effect on the in vitro cytotoxicity of TiO2 nanocrystalline film. The grain size was in the scope of 10～120nm. The in vitro cytotoxicity rating of anatase and rutile TiO2 nanocrystalline film is 1, which meet the requirements of ISO 10993-5:1999 for the cytotoxicity of biomaterials.3. The leaching time, three days and sixty days respectively, had no effect on the in vitro cytotoxicity of TiO2 nano crystalline film, thus indicating that nanocrystalline thin film is a very stable structure material in a physiological environment.4. UV has no influence on the in vitro cytotoxicity of TiO2 nanocrystalline film. But it has improved the biocompatibility of TiO2 nanocrystalline film slightly.更多还原