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.     

国产钛镍合金血管支架的生物相容性研究

采用国产钛镍形状记忆合金制成４ｍｍ内径的血管支架,通过导管置入８只正常犬的双侧髂动脉。观察１－６个月,发现支架表面业层新生内膜覆盖,光镜及电观察新生内膜表层为血管内皮样细胞,国产钛镍合金血管要有很好的生物相容性     

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。     

不同类型脑血管支架材料的特点及临床应用

背景：随着基础研究、临床应用,以及血管支架材料的不断发展,血管内支架置入治疗已被广泛应用于脑血管疾病治疗中。 目的：综述这几种支架材料的特点及临床应用情况。 方法：应用计算机检索CNKI数据库、万方数据库、PubMed数据库从建库到2014年3月的相关文献,中文检索关键词为“脑血管病,支架,生物相容性”,英文检索关键词为“cerebrovascular disease,stents,biocompatibility”。 结果与结论：按释放方式可将脑血管支架分为球囊扩张式支架与自膨式支架。最初应用的支架材料主要为裸金属材料,由记忆合金、医用不锈钢、钽、钴、镍钛合金等制成。由于金属支架置入后会释放金属离子,易致血栓形成,再狭窄率高,后来对其表面进行改性,出现了涂层支架与覆膜支架。支架置入治疗的围手术期并发症主要有过度灌注综合征、急性血栓形成、血管破裂和远端血管栓塞、血管痉挛和穿刺相关并发症,远期并发症主要是支架置入后再狭窄问题。相信随着科技的进步,支架材料和制作工艺的不断改进,血管支架置入治疗将更加安全有效。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：     

羟基磷灰石表面修饰人工角膜钛支架的体内生物相容性

背景：纯钛人工角膜支架在临床应用中的并发症发生率较高,因此寻找一种生物相容性高的人工角膜支架材料一直是国内外研究的重点和热点。目的：观察羟基磷灰石表面修饰人工角膜钛支架的体内生物相容性。方法：取新西兰白兔27只,制作右眼角膜碱烧伤模型,造模后立即均分为3组,实验组右眼植入经过羟基磷灰石表面修饰的人工角膜钛支架,对照组右眼植入人工角膜钛支架,空白对照组右眼仅制备囊袋而不植入支架。术后2,4,16周取兔右眼角膜组织,进行病理组织学观察及扫描电镜观察。结果与结论：术后16周,3组间炎性细胞与纤维细胞数量比较差异均无显著性意义。随着时间的延长,实验组角膜组织逐渐增多,纤维组织逐渐增厚,细胞外基质附着逐渐增加,角膜组织贴附密集度、细胞外基质附着密集度及组织愈合度均优于对照组及空白对照组。表明羟基磷灰石表面修饰人工角膜钛支架具有良好的生物相容性,可有效促进角膜细胞增生,有利于角膜血管化。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     

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。     

抗血管平滑肌增生和迁移的药物涂层与支架置入后再狭窄

背景：抑制血管平滑肌细胞增殖和血管内膜的增生而不影响血管内皮愈合的药物涂层是研制新型药物洗脱支架和防治支架内再狭窄的新策略。 目的：综述抗血管平滑肌细胞增生和迁移药物涂层支架的研究进展。 方法：由第一作者应用计算机检索维普数据库中与抗血管平滑肌细胞增生和迁移药物涂层支架置入治疗心血管疾病有关的文献,检索时限1998-01/2011-10。关键词：心血管疾病;药物涂层支架;血管平滑肌;细胞增生;细胞迁移。对资料进行初审,并查看每篇文献后的引文。纳入相关文献25篇,中文15篇,英文10篇。 结果与结论：目前临床应用最广的抗血管平滑肌细胞增生和迁移的涂层药物是雷帕霉素和紫杉醇。研究表明,雷帕霉素支架表面携带的雷帕霉素和紫杉醇支架表面携带的紫杉醇均能有效地降低支架置入后再狭窄及临床靶血管血运重建率。目前国内大多数研究仅为小样本、单中心、非随机对照试验,其更长期的疗效和安全性有待更长期的随访和多中心随机对照研究来证明。     

内皮祖细胞在膀胱细胞外基质上的生长及分化

背景：传统的组织工程膀胱支架材料本身无血管结构,植入体内后面临血管化不足的问题。 目的：观察内皮祖细胞与膀胱细胞外基质的生物相容性。 方法：分离培养兔内皮祖细胞,种植于兔膀胱细胞外基质上与其复合培养。将复合生长材料植入兔背部皮下检测其组织相容性。 结果与结论：兔内皮祖细胞能够在膀胱细胞外基质表面正常黏附、生长、增殖,细胞形态良好。内皮祖细胞-膀胱细胞外基质植入兔体内后1周时,可见材料周围炎症反应明显,粘连严重,出血较多;苏木精-伊红染色可见组织中较多炎性细胞浸润,胶原及弹性纤维排列松散。植入后8周时可见材料已降解成碎细丝状,与周围组织融合生长在一起,但质地略脆,易出血;苏木精-伊红染色可见组织中已无明显炎症细胞浸润反应,胶原及弹性纤维排列紧密并且有新生血管长入其中。结果表明内皮祖细胞与膀胱细胞外基质具有良好的相容性,复合培养物与体内组织具有良好的相容性。     

罗格列酮对CD34修饰脱细胞血管支架体内生长的影响

背景：早期研制的脱细胞血管基质支架上预载CD34+抗体会促进其再内皮化,但同时会加重支架内血管内膜增生。国内外研究证实过氧化物酶增殖体受体γ激动剂罗格列酮在体外可抑制平滑肌细胞增生及迁移,可减少血管损伤处内膜增生。 目的：进一步验证过氧化物酶增殖体受体γ激动剂罗格列酮对CD34抗体修饰脱细胞血管支架体内移植后平滑肌细胞生长及内膜增生的影响。 方法：获取新鲜兔颈动脉,应用光化学偶联法将CD34抗体固定到去细胞光氧化的血管支架上,构建抗体修饰的组织工程血管。将制备的血管分别移植于实验兔的颈动脉上,其中对照组予以移植单纯光氧化处理的脱细胞血管,CD34组予以CD34抗体预载的血管,罗格列酮组移植CD34抗体预载的血管并予喂养罗格列酮。 结果与结论：移植后10 d：对照组移植血管内皮样细胞数量稀少,CD34组和罗格列酮组可见较多的内皮样细胞覆盖;CD34组血管内膜较罗格列酮组厚,α-SMA染色显示CD34组血管平滑肌细胞数量较后者为多,其差异有显著性意义。移植后30 d：CD34组和罗格列酮组血管内皮样细胞基本覆盖管腔全层,对照组内皮样细胞数量仍较少;另外,CD34组血管内膜及管壁中可见大量的平滑肌样细胞及细胞外基质沉积,而罗格列酮组血管结构中平滑肌样细胞数量相对较少,内膜增生亦较轻。提示CD34修饰脱细胞血管支架可促进其内皮细胞的增生,罗格列酮可抑制血管支架中平滑肌细胞的增殖,减少内膜增生。     

不同生物材料构建血管支架的组织相容性

背景：组织工程支架已成为近年来研究的热点,不同材料构建的组织工程血管支架的特点各异,植入后的生物相容性、感染、再狭窄是临床上面临的难点与重要研究课题。 目的：文章综述了不同材料构建的组织工程血管支架的特点和生物相容性等的研究进展,以便寻找临床最佳的生物材料支架。 方法：应用计算机检索CNKI和PubMed数据库中2002-01/2010-12关于细菌生物膜耐药机制的文章,在标题和摘要中以“组织工程,血管支架,相容性,感染,再狭窄”或“Tissue engineering,stents,compatibility,infection,restenosis ”为检索词进行检索。选择文章内容与血管支架的特点和生物相容性相关,同一领域文献则选择近期发表或发表在权威杂志文章。初检得到285篇文献,根据纳入标准选择23篇文章进行综述。 结果与结论：天然材料包含有生物信息(如特殊的氨基酸序列),可促进细胞吸附或使细胞保留分化功能,人工合成材料的优点是它们的强度、降解速度、微结构和渗透性均可在生产过程中进行控制;若生物材料和高分子可降解材料相结合,将两者按照一定的方法组合构建成一种复合基质,发挥两者各自的优势,便能更好地满足血管组织工程的要求,构建出性能良好的组织工程化血管。     

Mesenchymal stem cell seeding promotes reendothelialization of the endovascular stent

This study is designed to make a novel cell seeding stent and to evaluate reendothelialization and anti-restenosis after the stent implantation. In comparison with cell seeding stents utilized in previous studies, Mesenchymal stem cells (MSCs) have advantages on promoting of issue repair. Thus it was employed to improve the reendothelialization effects of endovascular stent in present work. MSCs were isolated by density gradient centrifugation and determined as CD29(+) CD44(+) CD34(-) cells by immunofluorescence and immunocytochemistry; gluten and polylysine coated stents were prepared by ultrasonic atomization spray, and MSCs seeded stents were made through rotation culture according to the optimized conditions that were determined in previous studies. The results from animal experiments, in which male New Zealand white rabbits were used, show that the reendothelialization of MSCs coated stents can be completed within one month; in comparison with 316L stainless steel stents (316L SS stents) and gluten and polylysine coated stents, the intimal hyperplasia and in-stent restenosis are significantly inhibited by MSCs coated stents. Endovascular stent seeded with MSCs promotes reendothelialization and inhibits the intimal hyperplasia and in-stent restenosis compared with the 316L SS stents and the gluten and polylysine coated stents.     

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.     

Growth inhibition of cultured smooth muscle cells by corrosion products of 316 L stainless steel wire

The potential cytotoxicity on vascular smooth muscle cells of corrosion products from 316 L stainless steel, one of most popular biomaterials of intravascular stents, has not been highlighted. In this investigation, 316 L stainless steel wires were corroded in Dulbecco's modified eagle's medium with applied constant electrochemical breakdown voltage, and the supernatant and precipitates of corrosion products were prepared as culture media. The effects of different concentrations of corrosion products on the growth of rat aortic smooth muscle cells were conducted with the [3H]-thymidine uptake test and cell cycle sorter. Both the supernatant and precipitates of corrosion products were toxic to the primary culture of smooth muscle cells. The growth inhibition was correlated well with the increased nickel ions in the corrosion products when nickel concentration was above 11.7 ppm. The corrosion products also changed cell morphology and induced cell necrosis. The cell growth inhibition occurred at the G0/G1 to S transition phase. Similar to our recent study of nitinol stent wire, the present investigation also demonstrated the cytotoxicity of corrosion products of 316 L stainless steel stent wire on smooth muscle cells, which might affect the poststenting vascular response.     

Long-term engraftment of bone marrow-derived cells in the intimal hyperplasia lesion of autologous vein grafts

Intimal hyperplasia of autologous vein grafts is a critical problem affecting the long-term patency of many types of vascular reconstruction. Within intimal hyperplasia lesions, smooth muscle cells are a major component, playing an essential role in the pathological process. Given that bone marrow-derived cells may differentiate into smooth muscle cells in the neointima of injured arteries, we hypothesized that the bone marrow may serve as a source for some of the smooth muscle cells within intimal hyperplasia lesions of vein grafts. To test this hypothesis, we used an established mouse model for intimal hyperplasia in wild-type mice that had been transplanted with bone marrow from a green fluorescent protein (GFP+/+) transgenic mouse. High-resolution confocal microscopy analysis performed 2 and 8 weeks after grafting demonstrated expression of GFP in 5.4 +/- 0.8% and 11.9 +/- 2.3%, respectively, of smooth muscle cells within intimal hyperplasia lesions. By 16 weeks, GFP expression in smooth muscle cells was not detected by immunohistochemistry; however, real-time PCR revealed that 20.2 +/- 1.7% of the smooth muscle cells captured from the neointima lesion by laser capture microdissection at 16 weeks contained GFP DNA. Our results suggest that bone marrow-derived cells differentiated into smooth muscle cells within the intimal lesion and may provide a novel clinical approach for decreasing intimal hyperplasia in vein grafts.     

Polytetrafluoroethylene-covered stents in the venous and arterial system: angiographic and pathologic findings in a swine model

BACKGROUND: Although polytetrafluoroethylene (PTFE) is now used as a covering in a wide variety of vascular stents, little is known about the resultant pathologic and angiographic changes in the arterial and venous system after stent deployment. METHODS: Atrium PTFE-covered stents were deployed in the abdominal aorta and the inferior vena cava (IVC) of two Yorkshire pigs. Angiograms were performed after deployment and at recatheterization. A complete histopathological exam was performed after sacrifice, and angiographic and histology findings were then compared between the two types of blood vessels. RESULTS: The arterial stents demonstrated no stenosis on angiography and minimal in-stent intimal proliferation by histopathology. A uniform layer of neointima coated the inside of the stent by 1 month with no obvious thrombus formation. In contrast, the venous stents demonstrated angiographic evidence of significant in-stent stenosis of variable degrees and the histology showed increased intimal hyperplasia with fibrin deposition. PTFE from both the arterial and venous stents had variable amounts of tissue ingrowth with cells observed to be growing into and through the PTFE fibers. CONCLUSIONS: Atrium PTFE-covered stents have excellent short-term angiography and histopathology in the arterial system, while stents in the venous system developed rapid in-stent intimal hyperplasia. PTFE fibers from both types of vasculature permitted cells to grow through and within them.     

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.     

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。