【作者】 孙大明；

【导师】 王贵学； 尹铁英；

【作者基本信息】 重庆大学 ， 生物医学工程， 2013， 硕士

【摘要】 动脉粥样硬化所致心脑血管疾病是危害人类健康的“头号杀手”。经皮冠状动脉介入术（Percutaneous Coronary Intervention, PCI）是治疗心脑血管病狭窄类病变的产用微创型治疗技术。药物洗脱支架（Drug-eluting stent, DES）是当前应用最为广泛的治疗血管病狭窄类病变的微创医疗器械。早期的DES较金属裸支架（Baremetal stent, BMS）的临床疗效有明显提高，特别是在抑制再狭窄方面。但长期的临床应用中发现，DES所导致的内皮化延迟、炎症反应、超敏反应等会引起亚急性或晚期不良临床事件，并造成极高的致死率。因此，DES的长期安全性问题多年来受到极大的关注。DES所造成的不良反应常与其设计密切相关，对DES进行优化设计，开发具有更高临床疗效和长期安全性的新一代DES是近年来国内外的研究热点。优秀的DES需要保证支架平台、药物、涂层三大因素间和谐互利关系，充分发挥各自功效。这使支架涂层在DES研究中占有极其重要的地位。一方面，涂层是目标血管壁与支架平台间的媒介；另一方面，涂层作为药物载体能有效地对支架表面进行修饰，提高其生物相容性。本研究通过对实验室自行开发的超声雾化喷涂装置的工作原理和实现方式的分析，总结了其应用中存在的问题。对其进行了优化设计，实现了装置加工工艺参数的可调节性，减小了加工过程中的设备与环境污染问题。然后，利用该装置对316L不锈钢支架的壳聚糖涂层制备工艺进行了优化。最后，对壳聚糖涂层质量从宏观到微观进行了检验，并采用体外扩张实验及细胞相容性试验对涂层的安全性进行了初步的评价。实验研究主要内容与结果：①通过对装置雾化模块、支架传动系统、半封闭系统的优化设计，使得装置雾化能力更稳定且雾粒更小（1~3μm），支架传动速度可在径向0~542rpm、轴向0~0.55m/s范围内自由调节，雾粒飞散情况得到改善，有效地提高了其适用性和安全性。②316L不锈钢支架表面涂装前酸洗预处理，能有效地去除表面污物并使表面微粗糙化，提高涂层粘附能力。采用改进后喷涂装置可完成316L不锈钢支架壳聚糖涂层的制备，利用分光光度法可测量涂覆量，设计正交实验分析发现加工行程数、载气压力、支架径向转速、轴向进给速度对涂覆量存在极显著性影响，并筛选出了加工行程数n=25、载气压力P=2Psi、支架径向转速r=60rpm、轴向进给速度v=1mm/s的最佳加工工艺参数组合。③对正交实验筛选出的最佳加工工艺参数下制备出的壳聚糖涂层，通过光学显微镜进行宏观质量检测发现涂层不存在喷涂死角，无涂层失效现象发生，涂层表面平整。采用扫描电子显微镜、色散能谱仪、原子力显微镜微观观察涂层发现涂层有效地修复了支架表面的细小缺陷，均匀性优良，有效降低了支架丝表面粗糙度。利用体外扩张实验、细胞粘附与增殖检测初步验证了涂层具有良好的植入安全性。更多还原

【Abstract】 Cardiovascular and cerebrovascular disease due to atherosclerosis is the “numberone killer of harm to human health”. Percutaneous coronary intervention (PCI) is thetreatment of cardiovascular and cerebrovascular disease narrow lesions producingminimally invasive treatment thechniques. At present, drug-eluting stents (DESs) arethe most widely used. Compared with early bare-metal stents (BMSs), DESs are moreeffective in treating coronary artery diseases, especially in inhibiting restenosis.However, delayed endonthelialization, inflammation, and hypersensitivity triggersubacute or late adverse events, caused a higher death rate, and thereby raise moreconcerns over the long-term safety of DESs. These problems are mostly associated withcurrent DES design. It is critically important to further improve and optimize DESdesign and apply newer strategies for developing next generation DES.These three components including metal stent backbone, active pharmacologicagent, and drug carrier should be harmoniously orchestrated to create a clinicallydesirable device that can eradicate ISR and other adverse complications. Stent coatingplays an extremely important role in the DES research. The one hand, the coating is anintermediary between the target vessel wall and stent platform; other hand, the coatingas a pharmaceutical carrier can be effectively modified stent surface to improvebiocompatibility. This study analyzes the existing ultrasonic atomizing spray deviceworks in the laboratory, and summarizes the problems in the application. We optimizedthe device, so that the processing parameters can be adjusted and equipment andenvironmental pollution is reduced. Then, optimize the preparation process of chitosancoating of316L SS stent with the improved device. Finally, examines the quality ofchitosan coating from macro to micro, and preliminary evaluated the safety of thecoating by in vitro expansion experiments and cell compatibility test.The main content and results of experimental study:①Trough the optimization design of atomization module, transmission system,semi-closed system, atomization capacity of the device becomes more stable and themist particles become smaller (1~3μm). The stent may allow free movement in the axial(0~0.55m/s)/radial (0~542rpm). Mist particles flying situation is improved. Itsapplicability and safety are improved effectively.②Pickling pretreatment of316L SS stent surface before painting can remove dirt effectively and micro-roughened the surface. Thus, Coating adhesion capacity has beenimproved. Improved spraying device can be used with the preparation of chitosancoating. The coating amount can be measured by spectrophotometry measurable.Analysis of orthogonal test results showed that the number of process engineering,carrier gas pressure, stent radial speed, feed rate extremely significant affect coatingamount. Filter out the best process parameter combinations(n=25, P=2psi, r=60rpm,v=1mm/s).③To Prepare chitosan coating under optimal process parameters, The macro qualitytesting found that the coating does not exist spraying corners, no coated failure occurred,smooth coating surface through the optical microscope. Microscopic observation ofthe coating found effective to repair small defects of the stent surface coatings, evenexcellent, effectively reducing the stent wire surface roughness using scanning electronmicroscopy, dispersive spectrometer, an atomic force microscope. Using in vitroexpansion experiments, cell adhesion and cell proliferation assay preliminarily verifiedthe coating has a good implant security.更多还原