生物可降解腔靜脈濾器的實驗研究
發(fā)布時間：2018-09-01 11:01
【摘要】：目的 1、研究采用先進(jìn)計算機(jī)輔助設(shè)計和激光雕刻技術(shù)制備生物可降解腔靜脈濾器（Biodegradable Vena Cava Filter，BVCF）的可行性，明確有中心線型BVCF與無中心線型BVCF、不銹鋼濾器的機(jī)械性能差異，研制有中心線型BVCF的釋放裝置。 2、通過BVCF體外測試實驗，評價BVCF的力學(xué)性性能、可輸送性能、捕獲血栓性能及降解性能。 3、研究BVCF的生物相容性，評價BVCF植入動物血管后不同時期的組織學(xué)變化以確定其植入血管的可行性；研究利用可降解腔靜脈濾器預(yù)防肺栓塞的可行性。 材料和方法 1、利用三維設(shè)計軟件設(shè)計BVCF外形，利用有限元軟件分析和優(yōu)化濾器設(shè)計。采用溶液鋪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、粘貼和熱定形的方法，制作生物可降解濾器。 2、對自行制作的BVCF進(jìn)行體外測試，包括力學(xué)性能、可輸送性能和捕獲血栓性能及降解性能的測試。 3、通過動物實驗研究BVCF的可行性。選擇實驗小型豬12只。隨機(jī)地將實驗動物分為四組，每組3只。前三組為實驗組，利用導(dǎo)管將BVCF置入小型豬的下腔靜脈。第四組不置入濾器，作為對照組。對每組動物分別注入2、5和8條血栓（長度2.5-3cm、直徑3-5mm），監(jiān)測動物的呼吸、心跳等生命體征。經(jīng)導(dǎo)管鞘注入造影劑，利用X線透視，觀察濾器捕獲血栓情況。血栓注入后1、6和12周，對實驗動物行增強(qiáng)CT檢查，觀察下腔靜脈濾器和肺動脈栓塞情況。每次影像檢查后，處死一組實驗動物。解剖并取出實驗動物放置濾器的下腔靜脈段，觀察濾器的位置、形態(tài)、內(nèi)膜包埋情況和表面血栓附著情況。取出實驗動物的雙肺，固定、染色、包埋、切片，行病理學(xué)分析，觀察肺栓塞部位，并對肺栓塞進(jìn)行分級，評價BVCF預(yù)防肺栓塞的效果。 結(jié)果 1、自行設(shè)計和制作了一種可降解的腔靜脈濾器。該濾器有5-8個側(cè)枝，通過牽拉中心線可以使側(cè)枝擴(kuò)張，使濾器固定在下腔靜脈內(nèi)。這些側(cè)枝形成兩道濾網(wǎng)，能夠捕獲流經(jīng)濾器的血栓。 2、對BVCF做體外測試，結(jié)果表明濾器兩相對側(cè)枝的徑向支撐力約為1.6N；BVCF可以利用導(dǎo)管通過微創(chuàng)介入手術(shù)輸送到下腔靜脈；利用自行制作的體外實驗裝置進(jìn)行血栓捕捉實驗，結(jié)果顯示該濾器能夠捕獲直徑最小為3mm的血栓；體外降解實驗結(jié)果表明經(jīng)過一周浸泡，濾器易碎且易崩解。 3、實驗組動物均成功地置入BVCF。在血栓注入實驗中，實驗組動物均存活，術(shù)中2頭實驗小型豬出現(xiàn)輕度呼吸頻率、心跳增快癥狀，其余實驗組小型豬生命體征平穩(wěn)，未出現(xiàn)呼吸困難、氣急、嗆咳等肺動脈栓塞癥狀；行下腔靜脈造影及增強(qiáng)CT可見下腔靜脈內(nèi)濾器段團(tuán)塊狀充盈缺損，提示濾器成功攔截了注入的血栓，，2頭出現(xiàn)癥狀小型豬行增強(qiáng)CT檢查確診發(fā)生周圍性肺動脈栓塞（Pulmonary Embolism，PE），其余實驗組小型豬CT掃描未見明確的肺動脈栓塞征象。對照組注入血栓后，不同程度地出現(xiàn)呼吸頻率加快、氣促等癥狀，其中注入8條血栓的小型豬，在術(shù)后當(dāng)天死亡，觀察肺臟可見大片狀楔形深紅色區(qū)域，考慮為出血性梗死，切面可見肺組織栓塞部位點片狀出血。組織切片結(jié)果顯示，濾器植入術(shù)后1周后內(nèi)膜部分覆蓋BVCF側(cè)枝，6周后內(nèi)膜覆蓋較為徹底，血管壁結(jié)構(gòu)正常，未見明顯炎性細(xì)胞浸潤，術(shù)后12周獲取的血管標(biāo)本，血管壁結(jié)構(gòu)正常，管腔通暢，濾器側(cè)枝部分降解。 結(jié)論 1、本項目設(shè)計和制作了一種新的可降解腔靜脈濾器。 2、體外測試結(jié)果顯示，這種中心線擴(kuò)張的可降解濾器的徑向支撐力接近于金屬濾器，能夠像金屬濾器一樣通過導(dǎo)管輸送，并固定在血管內(nèi)，且具有較高的血栓捕獲率。 3、動物實驗結(jié)果顯示，該濾器能夠有效地捕獲注入下腔靜脈的致命性血栓，防止肺栓塞的發(fā)生。可降解濾器存在的問題是：濾器的輸送不如金屬濾器方便，另外濾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.
【學(xué)位授予單位】：中國人民解放軍醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R318.08
本文編號：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.
【學(xué)位授予單位】：中國人民解放軍醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R318.08
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