中国组织工程研究

中国组织工程研究 ›› 2022, Vol. 26 ›› Issue (22): 3474-3479.doi: 10.12307/2022.273

• 复合支架材料 composite scaffold materials • 上一篇    下一篇

胸主动脉共用覆膜和裸支架系统体内血栓形成的评价

马  静1，2，郑利萍1，2，孙  吉1，2，杨晓琴1，2，蒲林云1，2，袁  暾1，2，梁  洁1，2   

  1. 1四川大学国家生物医学材料工程技术研究中心，四川省成都市   610064；2四川医疗器械生物材料和制品检验中心，四川省成都市   610064
  • 收稿日期:2020-12-03 修回日期:2021-01-16 接受日期:2021-06-02 出版日期:2022-08-08 发布日期:2022-01-12
  • 通讯作者: 梁洁，教授，高级工程师，四川大学国家生物医学材料工程技术研究中心，四川省成都市 610064；四川医疗器械生物材料和制品检验中心，四川省成都市 610064
  • 作者简介:马静，女，1988年生，四川省成都市人，回族，2014年西南民族大学毕业，硕士，工程师，主要从事医疗器械生物安全性评价研究。 郑利萍，女，1986年生，四川省南充市人，汉族，2019年四川大学毕业，工程师，主要从事医疗器械生物安全性评价研究。
  • 基金资助:
    国家重点研发计划(2018YFC1106800)，课题负责人：梁洁；四川省重点研发项目(2020YFS0462)，项目负责人：袁暾

Evaluation of thrombosis in thoracic aortic stent system with covered stent and bare stent

Ma Jing1, 2, Zheng Liping1, 2, Sun Ji1, 2, Yang Xiaoqin1, 2, Pu Linyun1, 2, Yuan Tun1, 2, Liang Jie1, 2   

  1. 1National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, Sichuan Province, China; 2Sichuan Testing Center for Biomaterials and Medical Devices, Chengdu 610064, Sichuan Province, China
  • Received:2020-12-03 Revised:2021-01-16 Accepted:2021-06-02 Online:2022-08-08 Published:2022-01-12
  • Contact: Liang Jie, Professor, Senior engineer, National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, Sichuan Province, China; Sichuan Testing Center for Biomaterials and Medical Devices, Chengdu 610064, Sichuan Province, China
  • About author:Ma Jing, Master, Engineer, National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, Sichuan Province, China; Sichuan Testing Center for Biomaterials and Medical Devices, Chengdu 610064, Sichuan Province, China Zheng Liping, Engineer, National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, Sichuan Province, China; Sichuan Testing Center for Biomaterials and Medical Devices, Chengdu 610064, Sichuan Province, China Ma Jing and Zheng Liping contributed equally to this paper.
  • Supported by:
    the National Key Research and Development Program, No. 2018YFC1106800 (to LJ); Sichuan Province Key Research and Development Project, No. 2020YFS0462 (to YT)

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摘要：

文题释义：
胸主动脉支架系统：该系统用于治疗Stanford B 型主动脉夹层，由胸主动脉覆膜支架和胸主动脉金属裸支架构成。支架平台材料多采用镍钛诺合金，覆膜材料多采用聚酯类和膨体聚四氟乙烯，支架的输送系统一般采用同轴式，通过支架自扩张方式来释放支架。
体内血栓形成：血栓形成实验是判定器械血液相容性的重要方法，特别是针对植入类器械。血栓形成过程主要在体内或半体内条件下发生，在流动或静止的血管或器械区域由凝血、血小板和白细胞激活产生。而体内血栓实验更接近临床最终用途，能更好地预测与评估该类器械的临床风险。一般来说，体内血栓形成实验通过模拟操作后的器械表面血栓情况、末端器官的血栓情况等结果来分析评价血栓的形成过程及程度，预测器械在使用过程中的风险。

背景：胸主动脉支架系统类器械一般由覆膜支架和金属裸支架及相应的输送系统构成，由于此类器械结构的复杂性，导致临床上可能带来更多关于血栓安全性的担忧。
目的：为覆膜支架和裸支架联合使用的植入血管类器械上市前安全性评价的设计和结果分析提供更完整的思路。
方法：选取3只实验猪，均植入胸主动脉支架系统，该系统包括胸主动脉支架系统输送器、胸主动脉支架系统覆膜支架、胸主动脉支架系统裸支架三部分，将覆膜支架植入实验动物的降主动脉段，并导入胸主动脉裸支架衔接于胸主动脉覆膜支架的远端，术中，对回撤至体外的输送器部分观察其表面血栓形成情况。术后7 d，取胸主动脉支架系统覆膜支架、裸支架与输送器部分，进行扫描电镜观察；取胸主动脉支架系统裸支架和覆膜支架接触部位血管，进行组织学观察。
结果与结论：①大体观察显示，实验动物重要脏器未见血栓形成和血栓相关病变，植入部位血管的管腔中未见血栓性闭塞。②扫描电镜显示，覆膜支架系统输送器与裸支架系统输送器表面均可见几微米至上百微米大小的血栓分布，覆膜支架、裸支架表面及与支架接触的血管表面均可见几微米至几百微米大小的血栓分布。③组织学观察显示，覆膜支架接触部位血管内膜增生，新生组织大多由纤维蛋白网络大量红细胞构成，组织内部有炎性细胞浸润，少量新生组织边缘可见炎性细胞聚集，新生组织中局部有新生小血管形成；裸支架接触部位血管内膜增生，新生组织多由坏死的细胞构成，局部有聚集的炎性细胞。④结果表明，覆膜支架和裸支架联合使用的植入类器械植入后对血管产生的影响因组成不同而不同，需要考虑支架本身组成的特殊性，结合其临床使用方式，针对各组成部分进行分别评价分析。

https://orcid.org/0000-0003-2514-1275 (马静) 

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

关键词: 胸主动脉支架系统, 植入血管器械, 体内血栓形成, 覆膜支架, 裸支架, 输送系统

Abstract: BACKGROUND: The thoracic aortic stent system instruments generally consist of covered stent, bare metal stent and corresponding delivery system. They may trigger more concerns about the safety of thrombosis in clinical practice by reason of the complexity in structure of such instruments. 
OBJECTIVE: To provide a more rational idea for the design and analysis of premarket safety evaluation of such implantable vascular devices combined with covered stent and bare stent.
METHODS: Three experimental pigs were selected and implanted with the thoracic aortic stent system. The system includes the thoracic aortic stent system transporter, covered stent and bare stent. The coated stent was inserted into the descending aorta of the experimental pig, and the bare stent was subsequently led in to concatenate the distal end of the covered stent. During the operation, the surface thrombosis of the extracorporeal part of the transporter was observed. Seven days after the surgery, the covered stent, transporter and bare stent were taken out to perform scanning electron microscopy. Meanwhile, the vessels contacted the bare stent and coated stent were separated to process histological observation.
RESULTS AND CONCLUSION: (1) Gross observation displayed that no thrombosis or thrombosis-related lesions were observed in the important organs of the experimental pigs, and no thrombotic occlusion was observed in the lumen of the blood vessels at the implantation site. (2) Scanning electron microscopy showed that thrombosis of several microns to hundreds of microns could be seen on the surface of the transporter of the coated stent system and the bare stent system, and thrombosis of several microns to hundreds of microns could be seen on the surface of the coated stent, bare stent and the vascular surface contacted with the stent. (3) Histological observation showed intimal hyperplasia at the contact site of the coated stent. Most of the new tissue was composed of fibrin network and a large number of red blood cells. Simultaneously, inflammatory cells were infiltrated inside the tissue, and inflammatory cell aggregation was observed at the edge of a few new tissues, and new small vessels were formed locally in the new tissues. Furthermore, the intima of the vessels at the contact site of the bare stent was proliferated, and the new tissue was mostly composed of necrotic cells, with local aggregation of inflammatory cells. (4) The results revealed that the influence of the implantable instruments used in combination with coated stents and bare stents on the blood vessels after implantation varied with different components. Consequently, it was required to consider the particularity of the composition of the stent itself and evaluate and analyze each component in combination with the way of its clinical usage.

Key words: thoracic aortic stent system, implantable vascular device, thrombosis in vivo, stent graft, bare stent, delivery system

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