砷涂层支架置入后的血管组织相容性

背景：研究认为,三氧化二砷可以抑制血管平滑肌细胞的增殖,促进其凋亡,那么砷对血管平滑肌细胞的增生是否也有同样的抑制作用,砷涂层血管支架能否与血管组织相容,早期较好地被血管内膜覆盖或达到减少内膜过度增生的作用？ 目的：观察砷涂层血管支架的血管组织相容性。 方法：取大耳白家兔14只,随机分为2组,分别在腹主动脉处植入砷涂层316 L不锈钢支架和316 L不锈钢裸支架,植入28 d后结扎支架部位血管的远端和近端,取下支架部位的血管行苏木精-伊红染色,光镜检查。 结果与结论：①大体观察：支架处的血管外径稍大于相邻处血管的外径,呈扩张状态,无肉眼可见的血栓,切开支架,支架表面可见光滑的新生内膜形成,新生内膜表面光滑。②光镜观察：支架丝位于血管的中层,中层平滑肌被压,支架丝周边,血管内膜平滑肌增生,使血管内膜增厚。支架丝的血管腔面可见新生的血管内膜形成并覆盖支架丝,支架丝与血管组织之间可见一薄层黑色物质,为涂层药物砷及其化合物,证明砷涂层支架可以被血管组织覆盖,具有良好的血管组织相容性。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程全文链接：     

载药复合支架的抗血管组织增生的研究

在氧化钛表面改性的国产不锈钢支架上涂覆一定量药物,制备出新型复合的抗增生载药支架.观察支架植入猪冠状动脉3个月后血管的开通情况及血管的内膜反应.将7枚国产的普通不锈钢支架和7枚制备的新型载药支架植入14头小型猪冠状动脉内,3个月后对支架植入段血管进行血管造影、光镜及电镜检查并进行免疫组织化学分析.冠状动脉造影显示动物处死前支架段血管开通率100%,支架X光下清晰可见,未经特殊抗血栓治疗,支架段血管内无血栓形成.扫描电镜显示两组支架表面都完全被血管内膜覆盖,表面光滑,无血栓形成.覆盖的血管内膜中内皮细胞沿血流方向成典型的铺路石状排列.组织学形态分析显示植入支架3个月后,所有支架植入段血管内膜都有明显的增生,增生内膜主要由细胞外基质和平滑肌细胞构成.结论:含有新型载药支架的冠状动脉血管段内膜增生厚度比普通不锈钢支架的冠状动脉血管段内膜增生厚度小,这种载药复合支架具有良好的应用前景,需扩大样本进行深入研究.     

CD34抗体包被支架预防兔损伤动脉支架内狭窄

目的： 观察CD34抗体包被支架能否减少和预防球囊损伤动脉支架内狭窄。方法：①用明胶作为包被底物对支架进行包被，然后再包被CD34抗体。②复制股动脉损伤家兔模型，损伤后即刻于右侧植入普通支架，左侧植入抗体支架；45 d后，观察支架内最狭窄处的百分率、支架内和支架两端的血管新生内膜增生。结果：45 d 时，抗体包被支架内的最狭窄百分数明显低于普通侧支架（16.13±3.93 vs 47.03±11.89，P<0.05）；抗体包被支架段动脉血管新生内膜百分数明显低于普通支架段动脉血管（49.64±6.40 vs 66.83±6.00，P<0.05）；抗体包被支架远心端血管的新生内膜增生比普通支架远心端血管明显减轻。但两者的近心端动脉无明显差别。结论：CD34抗体包被支架能够有效减轻受损动脉支架内狭窄的发生。     

犬股动脉支架植入术后内膜增生与中膜损伤的关系

血管支架术后再狭窄的发生是一个多因素参与的复杂过程 ,其中球囊扩张、支架释放造成内弹力板断裂、中膜平滑肌损伤 ,继而血栓形成 ,炎性反应 ,生长因子释放 ,中层平滑肌细胞迁移、增生 ,最终新生内膜形成为其主要机制[1 ] 。本研究将记忆合金支架植入犬股动脉制作再狭窄模型 ,观察支架造成的犬股动脉中膜损伤程度与新生内膜大小的关系。1　材料和方法1 1　实验材料 :镍钛记忆合金编织型网格支架 :规格 :Φ4×13ｍｍ ;恢复温度 :33℃ ;(北京有色金属研究院记忆合金室提供 )1 2　动物模型制备 :杂种犬 18只 ,雌雄不限 ,体重 18～ 2 2ｋｇ。5 …     

支架置入兔颈动脉后平滑肌细胞增殖及c—myc基因的表达

目的 观察兔颈动脉内支架置入后,血管平滑肌细胞（VSMC）的增殖及c-myc原癌基因的表达。方法 将国产铂－铱合金支架置入16只家兔颈动脉,术后7、14、30和90d处死动物,行苏木素伊红（HE）和Masson三色染色、c-myc蛋白免疫组化染色及原位杂交。用透射电镜观察术后14d,VSMC超微结构的变化。结果 术后7d,中膜VSMC由收缩型变为合成型,内弹力板消失,偶见炎性细胞浸润,1例血管腔内出现不完全血栓形成。术后14d,新生内膜增生明显,主要由合成型过渡型VSMC组成。术后30d,新生内膜增生更加明显,主要为收缩型和少量过渡型VSMC及细胞外基质组成。术后90d,内弹力板恢复为弯曲的连续状,其上附着多层内皮细胞,VSMC为收缩型,术后14d透射电镜显示,合成型VSMC呈圆形或椭圆形,粗面内质网及线粒体非常丰富。支架置入后,兔颈动脉新生内膜中c-myc蛋白免疫组化及原位杂交均呈阳性,正常对照血管呈阴性。结论 兔颈动脉内置入支架后,可引起VSMC中c-myc基因表达增强,其与VSMC的增殖密切相关,在支架内再狭窄的形成中发挥重要作用。     

支架植入动脉后的血流动力学特性的研究方法

支架植入术是当今治疗动脉粥样硬化冠心病的一个非常重要的方法，而支架内血栓和新生内膜增生所致的再狭窄是导致冠脉内支架植入术失败的主要原因。大量研究表明支架的血流动力学特性影响了血栓的形成和新生内膜的增生，从而导致了支架内的再狭窄。我们回顾了病变血管支架术的重要性及其存在的问题，通过分析支架血流动力学特性的研究方法，综述了该领域的研究成果和进展。     

表面磁性膜医用316L不锈钢支架对兔髂动脉内膜增殖的影响

目的 研究表面磁性膜医用316L不锈钢支架对新西兰大白兔髂动脉新生内膜增殖的影响.方法 通过动物体内支架植入,采用定量冠脉造影、光学显微镜图像技术观察不同支架对新生内膜增殖和再狭窄的影响.结果 与普通裸支架相比,表面磁性膜支架可以抑制支架植入后的新生内膜增殖和再狭窄,植入3月后应用表面磁性膜支架和普通裸支架的管腔面积分别为(2.78±0.40)mm2和(2.07±0.62)mm2,再狭窄率分别为3.3%和16.7%,且可能与磁场强度相关.结论 表面磁性膜支架对经皮冠状动脉介入治疗术后的再狭窄可能具有防治作用.     

瑞舒伐他汀对Medtronic球囊导管损伤大鼠颈动脉平滑肌细胞增殖及凋亡的影响

背景:球囊扩张及支架置入后再狭窄、管腔丢失等问题制约了支架置入治疗的进一步发展,血管内膜增殖和凋亡在再狭窄中的作用及干预方法尚在积极探索中。目的:采用Medtronic球囊建立大鼠颈动脉球囊损伤模型,观察瑞舒伐他汀对球囊损伤大鼠颈动脉平滑肌细胞增殖及凋亡的影响。方法:将雄性SD大鼠随机数字表法分为球囊损伤组和治疗组。均采用Medtronic球囊建立大鼠颈动脉球囊损伤模型,并取球囊损伤组大鼠的右侧颈总动脉(未行球囊损伤)作为正常对照。治疗组于球囊损伤前3d始连续给予瑞舒伐他汀5mg/(kg·d)灌胃,球囊损伤组给予9g/L氯化钠溶液灌胃。术后7,14d取颈总动脉进行苏木精-伊红染色,免疫组织化学检测SMα-actin、增殖细胞核抗原,采用TUNEL法检测平滑肌细胞凋亡情况。结果与结论:与球囊损伤组比较,治疗组造模后14d,损伤血管新生内膜面积、新生内膜/中膜面积比值明显减少(P0.05),管腔面积增加26%;增殖细胞核抗原阳性细胞率降低,凋亡阳性细胞率增高(P0.05)。提示支架置入球囊损伤前给予瑞舒伐他汀可抑制大鼠颈动脉球囊损伤后新生内膜增生及新生内膜细胞的增殖,促进平滑肌细胞的凋亡,从而减少动脉新生内膜形成,抑制再狭窄。     

人子宫内膜异位症裸鼠模型的血管生成

背景:有研究表明子宫内膜异位症的发生发展与新生血管关系密切,抗血管生成有可能成为治疗子宫内膜异位症的有效手段。目的:建立人子宫内膜异位症裸鼠模型,观察异位病灶血管生成情况。方法:采用腹腔注射人子宫内膜碎屑的方法建立子宫内膜异位症裸鼠模型,光镜下观察异位病灶的形态学特点,用免疫组织化学染色法检测裸鼠在位内膜及异位内膜血管内皮生长因子表达水平及微血管密度。结果与结论:实验裸鼠异位病灶在光镜下呈现增生期子宫内膜形态特点;异位内膜较在位内膜血管内皮生长因子的表达有增多趋势,并有大量微血管形成。结果提示,实验成功建立了人子宫内膜异位症裸鼠模型,异位病灶中存在活跃的新生血管。     

国产钛镍形状记忆合金管内支架的模拟力学测量

利用液压方法测量国产钛镍形状记忆合金交叉网格血管内支架的力学性能的试验方法。并通过与平板压缩试验和包裹拉伸试验结果的比较 ,说明这是一种能近似模拟支架体内力学环境的自动测量方法 ,具有直观性好、可重复程度高等优点。该装置的研制及应用将提高我国血管内支架的研制和临床应用水平     

镍钛形状记忆合金血管内支架组织相容性实验研究

将锥形记忆合金支架分别植入６只猪右侧髂动脉。用以研究镍钛形状记忆合金血管内支架生物相容性，支架植入前入植入后８个月，观测动物血常规，肝肾功能以及毛发中镍钛元素含量，均无明显变化（Ｐ〉０．０５），支架植入后８个月处死动物，全身重要脏器（肝、脾、肾、肺、心、脑等）病理学检查结构正常，无淋巴细胞和单核细胞浸润，支架植入部位上游血管壁内膜光滑，内皮细胞结构正常，内弹力板完整，支架植入段为完整肉芽组织阻塞，     

Investigation of surface endothelialization on biomedical nitinol (NiTi) alloy: Effects of surface micropatterning combined with plasma nanocoatings

Plasma nanocoated films with trimethylsilane-oxygen monomers showed outstanding biocompatibility in our previous studies. In this study, endothelialization on biomedical nitinol alloy surfaces was systematically investigated. Our study focuses on elucidating the effects of surface micropatternings with micropores and microgrooves combined with plasma nanocoating. Plasma nanocoatings with controlled thickness between 40 and 50 nm were deposited onto micropatterned nitinol surface in a direct current plasma reactor. Bovine aortic endothelial cells were cultured in vitro on these nitinol samples for 1, 3 and 5 days. It was found that rougher surfaces could enhance cell adhesion compared with the smoother surfaces; the surfaces patterned with micropores showed much more endothelialization than microgrooved surface after a 3 days culture. The cell culture results also showed that plasma nanocoatings significantly further increased cell proliferation and cell adhesion on the micropatterned nitinol surfaces, as compared with non-plasma nanocoated surface of nitinol samples. The surface micropatternings combined with plasma nanocoatings could improve the cell adhesion and accelerate surface endothelialization after implantation of intravascular stents, which is expected to reduce in-stent restenosis.     

Thin film nitinol covered stents: design and animal testing

Interventionalists in many specialties have the need for improved, low profile covered stents. Thin films of nitinol (<5-10 microns) could be used to improve current covered stent technology. A "hot target" sputter deposition technique was used to create thin films of nitinol for this study. Covered stents were created from commercially available balloon-inflatable and self-expanding stents. Stents were deployed in a laboratory flow loop and in four swine. Uncovered stent portions served as controls. Postmortem examinations were performed 2-6 weeks after implantation. In short-term testing, thin film nitinol covered stents deployed in the arterial circulation showed no intimal proliferation and were easily removed from the arterial wall postmortem. Scanning electron microscopy showed a thin layer of endothelial cells on the thin film, which covered the entire film by 3 weeks. By contrast, significant neointimal hyperplasia occurred on the luminal side of stents deployed in the venous circulation. Extremely low-profile covered stents can be manufactured using thin films of nitinol. Although long-term studies are needed, thin film nitinol may allow for the development of low-profile, nonthrombogenic covered stents.     

The cytotoxicity of corrosion products of nitinol stent wire on cultured smooth muscle cells

Although nitinol is one of most popular materials of intravascular stents, there are still few confirmative biocompatibility data available, especially in vascular smooth muscle cells. In this report, the nitinol wires were corroded in Dulbecco's modified Eagle's medium with constant electrochemical breakdown voltage and the supernatant and precipitates of corrosion products were prepared as culture media. The dose and time effects of different concentrations of corrosion products on the growth and morphology of smooth muscle cells were evaluated with [(3)H]-thymidine uptake ratio and cell cycle sorter. Both the supernatant and precipitate of the corrosive products of nitinol wire were toxic to the primary cultured rat aortic smooth muscle cells. The growth inhibition was correlated well with the increased concentrations of the corrosion products. Although small stimulation was found with released nickel concentration of 0.95 +/- 0.23 ppm, the growth inhibition became significant when the nickel concentration was above 9 ppm. The corrosion products also altered cell morphology, induced cell necrosis, and decreased cell numbers. The cell replication was inhibited at the G0-G1 to S transition phase. This was the first study to demonstrate the cytotoxicity of corrosion products of current nitinol stent wire on smooth muscle cells, which might affect the postimplantation neointimal hyperplasia and the patency rate of cardiovascular stents.     

3-羟基丁酸与3-羟基己酸共聚酯的血管内生物相容性

背景：可降解聚合材料3-羟基丁酸与3-羟基己酸共聚酯(3-hydroxybutyrate-co- 3-hydroxyhexanoate, PHBHHx)具有良好的机械性能和生物可降解性。 目的：在体研究PHBHHx的血管内生物相容性。 方法：采用脱细胞羊肺动脉为支架,以PHBHHx涂层,构建复合补片,植入新西兰兔腹主动脉内,以脱细胞未涂层羊肺动脉片作为对照。分别于植入后第1,4,12周取出移植补片进行组织学、免疫荧光染色、扫描电镜和钙含量测定。 结果与结论：复合补片管腔面光滑无血栓,内膜增生适度,再细胞化完全;免疫荧光染色可见新生内膜组织中类内皮细胞呈CD31阳性反应,单层连续排列,间质细胞呈平滑肌肌动蛋白阳性反应;复合补片的钙含量明显低于未涂层羊肺动脉片。说明PHBHHx的血管内生物相容性满意,是心血管组织工程较为理想的腔内涂层材料。     

Increased corrosion resistance of stent materials by converting current surface film of polycrystalline oxide into amorphous oxide

Current efforts of new stent technology have been aimed largely at the improvement of intravascular stent biocompatibility. Among the chemical characteristics of metallic stents, surface oxide corrosion properties are paramount. Using our unique technique, the currently marketed 316 L stainless steel and nitinol stent wires covered with polycrystalline oxide were chemically etched and then passivated to form amorphous oxide. Excellent metallic-stent corrosion resistance with an amorphous oxide surface was demonstrated in our previous in vitro study. For in vivo validation, we compared the corrosion behavior of different oxide surfaces on various forms of test wires in the abdominal aorta of mongrel dogs using open-circuit potential and cyclic anodic polarization measurements. After conduction, the retrieved test wires were observed under scanning electron microscope. No passivity breakdown was found for wires covered with amorphous oxide, while wires with polycrystalline oxide showed breakdown at potentials between +0.2 to + 0.6 V. It has been proven that severe pitting or crevice corrosion occurred on the surface of polycrystalline oxide, while the surface of amorphous oxide was free of degradations in our experiment. We have demonstrated that this amorphous oxide coating on metallic material provides better corrosion resistance, not only in vitro but also in vivo, and it is superior not only in strength safety but also in medical device biocompatibility.     

Inflammation and impaired wound healing after zotarolimus-eluting stent implantation

An 86-year-old man died suddenly 5 months after implantation of a zotarolimus-eluting stent. Two zotarolimus-eluting stents were placed to treat a highly calcified diffuse lesion in the proximal-to-mid right coronary artery. The lesion was fully covered by the two stents, and intravascular ultrasound showed complete stent apposition. However, an X-ray at autopsy showed that the proximal stent was fractured. Although we thought that thrombotic occlusion at the fracture site might have caused his sudden death, no thrombus was present. In addition, in the other sites where the stents were optimally dilated, there was stent malapposition and peri-strut inflammation including macrophage infiltration, giant cells, polymer phagocytosis, and neovascularization in the neointima. Even with a second-generation drug-eluting stent, such as the zotarolimus-eluting stent, wound healing may be impaired at the stent-injured vessel site.     

Influence of surface microroughness by plasma deposition and chemical erosion followed by TiO2 coating upon anticoagulation, hydrophilicity, and corrosion resistance of NiTi alloy stent

Two different surface modification techniques were used to change the surface morphology and roughness of stents at the micrometer level, and eventually improve their surface adhesion properties with respect to endothelial cells. One was chemical erosion followed by sol-gel TiO(2) coating, and the other was low temperature gas plasma deposition. After surface modification, the biocompatibility including the anticoagulation properties, hydrophilicity, and corrosion resistance of these stents was evaluated. It was found that both techniques could change the surface morphology of the stents with microroughness. In comparison with the control, the treated NiTi alloy intravascular stents showed increased surface hydrophilicity and enhanced anticoagulation properties. However, the corrosion properties of the stents were not improved significantly.     

冠状动脉内可吸收的镁合金支架

背景：目前以钴铬合金为基础的冠状动脉内药物洗脱支架不能从根本上解决亚急性血栓形成和再狭窄问题,于是生物可吸收支架成为关注的焦点。 目的：评估自行设计制作冠状动脉内可吸收镁合金支架的生物相容性、有效性和安全性。 方法：35只犬均于冠状动脉和/或股动脉置入可吸收镁合金支架1枚,分别于支架置入后24 h、3 d、5 d、1周、2周、3周、4周(n=5)复查冠状动脉及血管造影后取材,分离支架段血管行组织病理观察及计算机图像分析,测量内弹力板面积、管腔面积、内膜增生面积及内膜增生面积百分比。 结果与结论：51枚支架成功置入35只犬的冠状动脉和股动脉,支架置入后不同时点各组冠状动脉及股动脉造影均证实管腔通畅,无狭窄病变,无血栓形成,置入后1周左右支架完全降解。组织病理学结果显示,支架置入后2周开始出现轻微内膜增生,内膜增生面积百分比随着时间的推移逐渐增高。提示自行研发的冠状动脉内可吸收镁合金支架1周内降解,置入早期未见明显炎症反应及血栓形成,再狭窄程度轻,具有良好的生物相容性,安全有效。