生物可降解腔静脉滤器的实验研究
发布时间：2018-09-01 11:01
【摘要】：目的 1、研究采用先进计算机辅助设计和激光雕刻技术制备生物可降解腔静脉滤器（Biodegradable Vena Cava Filter，BVCF）的可行性，明确有中心线型BVCF与无中心线型BVCF、不锈钢滤器的机械性能差异，研制有中心线型BVCF的释放装置。 2、通过BVCF体外测试实验，评价BVCF的力学性性能、可输送性能、捕获血栓性能及降解性能。 3、研究BVCF的生物相容性，评价BVCF植入动物血管后不同时期的组织学变化以确定其植入血管的可行性；研究利用可降解腔静脉滤器预防肺栓塞的可行性。 材料和方法 1、利用三维设计软件设计BVCF外形，利用有限元软件分析和优化滤器设计。采用溶液铺膜法制作可降解高分子聚左旋乳酸（Poly-L-Lactic Acid，PLLA）薄膜，然后利用切割、粘贴和热定形的方法，制作生物可降解滤器。 2、对自行制作的BVCF进行体外测试，包括力学性能、可输送性能和捕获血栓性能及降解性能的测试。 3、通过动物实验研究BVCF的可行性。选择实验小型猪12只。随机地将实验动物分为四组，每组3只。前三组为实验组，利用导管将BVCF置入小型猪的下腔静脉。第四组不置入滤器，作为对照组。对每组动物分别注入2、5和8条血栓（长度2.5-3cm、直径3-5mm），监测动物的呼吸、心跳等生命体征。经导管鞘注入造影剂，利用X线透视，观察滤器捕获血栓情况。血栓注入后1、6和12周，对实验动物行增强CT检查，观察下腔静脉滤器和肺动脉栓塞情况。每次影像检查后，处死一组实验动物。解剖并取出实验动物放置滤器的下腔静脉段，观察滤器的位置、形态、内膜包埋情况和表面血栓附着情况。取出实验动物的双肺，固定、染色、包埋、切片，行病理学分析，观察肺栓塞部位，并对肺栓塞进行分级，评价BVCF预防肺栓塞的效果。 结果 1、自行设计和制作了一种可降解的腔静脉滤器。该滤器有5-8个侧枝，通过牵拉中心线可以使侧枝扩张，使滤器固定在下腔静脉内。这些侧枝形成两道滤网，能够捕获流经滤器的血栓。 2、对BVCF做体外测试，结果表明滤器两相对侧枝的径向支撑力约为1.6N；BVCF可以利用导管通过微创介入手术输送到下腔静脉；利用自行制作的体外实验装置进行血栓捕捉实验，结果显示该滤器能够捕获直径最小为3mm的血栓；体外降解实验结果表明经过一周浸泡，滤器易碎且易崩解。 3、实验组动物均成功地置入BVCF。在血栓注入实验中，实验组动物均存活，术中2头实验小型猪出现轻度呼吸频率、心跳增快症状，其余实验组小型猪生命体征平稳，未出现呼吸困难、气急、呛咳等肺动脉栓塞症状；行下腔静脉造影及增强CT可见下腔静脉内滤器段团块状充盈缺损，提示滤器成功拦截了注入的血栓，，2头出现症状小型猪行增强CT检查确诊发生周围性肺动脉栓塞（Pulmonary Embolism，PE），其余实验组小型猪CT扫描未见明确的肺动脉栓塞征象。对照组注入血栓后，不同程度地出现呼吸频率加快、气促等症状，其中注入8条血栓的小型猪，在术后当天死亡，观察肺脏可见大片状楔形深红色区域，考虑为出血性梗死，切面可见肺组织栓塞部位点片状出血。组织切片结果显示，滤器植入术后1周后内膜部分覆盖BVCF侧枝，6周后内膜覆盖较为彻底，血管壁结构正常，未见明显炎性细胞浸润，术后12周获取的血管标本，血管壁结构正常，管腔通畅，滤器侧枝部分降解。 结论 1、本项目设计和制作了一种新的可降解腔静脉滤器。 2、体外测试结果显示，这种中心线扩张的可降解滤器的径向支撑力接近于金属滤器，能够像金属滤器一样通过导管输送，并固定在血管内，且具有较高的血栓捕获率。 3、动物实验结果显示，该滤器能够有效地捕获注入下腔静脉的致命性血栓，防止肺栓塞的发生。可降解滤器存在的问题是：滤器的输送不如金属滤器方便，另外滤器降解速度需要加快。
[Abstract]:objective
1. The feasibility of biodegradable vena cava filter (BVCF) fabricated by advanced computer aided design and laser engraving technology was studied. The difference of mechanical properties between BVCF with central line type and BVCF without central line type and stainless steel filter with central line type was clarified.
2. The mechanical properties, transportability, thrombus capture and degradation of BVCF were evaluated by in vitro test.
3. To study the biocompatibility of BVCF, to evaluate the histological changes of BVCF at different stages after implantation in order to determine the feasibility of BVCF implantation, and to study the feasibility of using biodegradable vena cava filter to prevent pulmonary embolism.
Materials and methods
1. The shape of BVCF was designed by three-dimensional design software, and the filter design was optimized by finite element analysis software. The biodegradable polymer poly-L-Lactic acid (PLLA) film was prepared by solution coating method, and then the biodegradable filter was fabricated by cutting, pasting and heat setting.
2. The self-made BVCF was tested in vitro, including mechanical properties, transportability, thrombus capture and degradation.
3, the feasibility of BVCF was studied through animal experiments. * 12 experimental miniature pigs were selected. The experimental animals were randomly divided into four groups, 3 in each group. The first three groups were the experimental group. * BVCF was placed into the inferior vena cava of the small pig by catheter. Fourth groups were not placed in the filter as the control group. Each group of animals was injected with 2,5 and 8 thrombus respectively (length 2.5-3cm, diameter 3-5M). After 1, 6, and 12 weeks, the thrombus was detected by enhanced CT, and the inferior vena cava filter and pulmonary embolism were observed. After each imaging examination, a group of experimental animals were sacrificed. The inferior vena cava segment of the filter was placed to observe the position, shape, embedding of the filter, and the attachment of the thrombus on the surface.
Result
1. A biodegradable vena cava filter has been designed and fabricated. The filter has 5-8 collateral branches, which can dilate by pulling the central line and fix the filter in the inferior vena cava.
2. In vitro test of BVCF showed that the radial support force of the lateral branches of the filter was about 1.6N; BVCF could be transported to the inferior vena cava via minimally invasive catheterization; thrombus capture experiment was carried out with a self-made in vitro experimental device, and the results showed that the filter could capture thrombus with a minimum diameter of 3mm; and biodegraded in vitro. The results showed that after one week of immersion, the filter was fragile and easy to disintegrate.
3, the animals in the experimental group were successfully implanted with BVCF. in the thrombus injection experiment. All the animals in the experimental group survived. During the operation, 2 * * pigs showed mild respiratory rate and increased heart rate. The other experimental group had stable vital signs and no symptoms of pulmonary embolism such as dyspnea, shortness of breath, cough and so on. Inferior vena cava angiography and enhanced CT were available. A confluent filling defect in the inferior vena cava filter segment showed that the filter successfully intercepted the thrombus. 2 cases of symptomatic miniature pigs underwent enhanced CT * Pulmonary Embolism (PE). The other experimental group * CT scan showed no definite signs of pulmonary embolism. There were respiratory symptoms such as rapid breathing, shortness of breath, and so on. * 8 of them were injected with a small amount of caged red in the lung. They were considered to be hemorrhagic infarcts. There were spotted hemorrhage in the lung tissue at the section. The results of histological sections showed that the intima was partially covered by BVCF after 1 weeks of implantation. The collateral vessels were covered thoroughly after 6 weeks, the structure of the vascular wall was normal, no obvious inflammatory cell infiltration was found. The vascular specimens obtained 12 weeks after operation showed normal vascular wall structure, unobstructed lumen and partial degradation of the collateral branches of the filter.
conclusion
1, a new biodegradable vena cava filter was designed and manufactured in this project.
2. In vitro test results show that the radial support force of this centrally expanded biodegradable filter is close to that of a metal filter, and it can be transported through a catheter like a metal filter and fixed in a blood vessel with a high thrombus capture rate.
3. Animal experimental results show that the filter can effectively capture lethal thrombus injected into the inferior vena cava and prevent pulmonary embolism.
【学位授予单位】：中国人民解放军医学院
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R318.08
本文编号：2216991
[Abstract]:objective
1. The feasibility of biodegradable vena cava filter (BVCF) fabricated by advanced computer aided design and laser engraving technology was studied. The difference of mechanical properties between BVCF with central line type and BVCF without central line type and stainless steel filter with central line type was clarified.
2. The mechanical properties, transportability, thrombus capture and degradation of BVCF were evaluated by in vitro test.
3. To study the biocompatibility of BVCF, to evaluate the histological changes of BVCF at different stages after implantation in order to determine the feasibility of BVCF implantation, and to study the feasibility of using biodegradable vena cava filter to prevent pulmonary embolism.
Materials and methods
1. The shape of BVCF was designed by three-dimensional design software, and the filter design was optimized by finite element analysis software. The biodegradable polymer poly-L-Lactic acid (PLLA) film was prepared by solution coating method, and then the biodegradable filter was fabricated by cutting, pasting and heat setting.
2. The self-made BVCF was tested in vitro, including mechanical properties, transportability, thrombus capture and degradation.
3, the feasibility of BVCF was studied through animal experiments. * 12 experimental miniature pigs were selected. The experimental animals were randomly divided into four groups, 3 in each group. The first three groups were the experimental group. * BVCF was placed into the inferior vena cava of the small pig by catheter. Fourth groups were not placed in the filter as the control group. Each group of animals was injected with 2,5 and 8 thrombus respectively (length 2.5-3cm, diameter 3-5M). After 1, 6, and 12 weeks, the thrombus was detected by enhanced CT, and the inferior vena cava filter and pulmonary embolism were observed. After each imaging examination, a group of experimental animals were sacrificed. The inferior vena cava segment of the filter was placed to observe the position, shape, embedding of the filter, and the attachment of the thrombus on the surface.
Result
1. A biodegradable vena cava filter has been designed and fabricated. The filter has 5-8 collateral branches, which can dilate by pulling the central line and fix the filter in the inferior vena cava.
2. In vitro test of BVCF showed that the radial support force of the lateral branches of the filter was about 1.6N; BVCF could be transported to the inferior vena cava via minimally invasive catheterization; thrombus capture experiment was carried out with a self-made in vitro experimental device, and the results showed that the filter could capture thrombus with a minimum diameter of 3mm; and biodegraded in vitro. The results showed that after one week of immersion, the filter was fragile and easy to disintegrate.
3, the animals in the experimental group were successfully implanted with BVCF. in the thrombus injection experiment. All the animals in the experimental group survived. During the operation, 2 * * pigs showed mild respiratory rate and increased heart rate. The other experimental group had stable vital signs and no symptoms of pulmonary embolism such as dyspnea, shortness of breath, cough and so on. Inferior vena cava angiography and enhanced CT were available. A confluent filling defect in the inferior vena cava filter segment showed that the filter successfully intercepted the thrombus. 2 cases of symptomatic miniature pigs underwent enhanced CT * Pulmonary Embolism (PE). The other experimental group * CT scan showed no definite signs of pulmonary embolism. There were respiratory symptoms such as rapid breathing, shortness of breath, and so on. * 8 of them were injected with a small amount of caged red in the lung. They were considered to be hemorrhagic infarcts. There were spotted hemorrhage in the lung tissue at the section. The results of histological sections showed that the intima was partially covered by BVCF after 1 weeks of implantation. The collateral vessels were covered thoroughly after 6 weeks, the structure of the vascular wall was normal, no obvious inflammatory cell infiltration was found. The vascular specimens obtained 12 weeks after operation showed normal vascular wall structure, unobstructed lumen and partial degradation of the collateral branches of the filter.
conclusion
1, a new biodegradable vena cava filter was designed and manufactured in this project.
2. In vitro test results show that the radial support force of this centrally expanded biodegradable filter is close to that of a metal filter, and it can be transported through a catheter like a metal filter and fixed in a blood vessel with a high thrombus capture rate.
3. Animal experimental results show that the filter can effectively capture lethal thrombus injected into the inferior vena cava and prevent pulmonary embolism.
【学位授予单位】：中国人民解放军医学院
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R318.08
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