中国组织工程研究

中国组织工程研究 ›› 2011, Vol. 15 ›› Issue (34): 6368-6374.doi: 10.3969/j.issn.1673-8225.2011.34.024

• 材料生物相容性 material biocompatibility • 上一篇    下一篇

新型可完全降解材料聚外消旋乳酸-三亚甲基碳酸酯聚合物体内降解行为和组织相容性

郭清奎1，吕志前1，张  袆1，李速明2，杨  建2   

  1. 1上海交通大学附属上海市第六人民医院胸心外科，上海市 200233
    2复旦大学材料科学系，上海市  200235
  • 收稿日期:2010-12-02 修回日期:2011-01-28 出版日期:2011-08-20 发布日期:2011-08-20
  • 通讯作者: 吕志前，教授，主任医师，博士生导师，上海交通大学附属上海市第六人民医院胸心外科，上海市 200233 luzhiqian@163.com
  • 作者简介:郭清奎☆，男，1978年生，安徽省涡阳县人，汉族，上海交通大学医学院在读博士，主治医师，主要从事胸心血管外科，研究方向为冠心病。 gqk1978@126.com
  • 基金资助:

    上海市科委项目(074107061)，项目名称：采用可降解生物材料研发新型冠状动脉涂层支架。

In vivo degradation behavior and histocompatibility of a novel fully biodegradable material: Poly trimethylene carbonate-Co-D, L-Lactide

Guo Qing-kui1, Lü Zhi-qian1, Zhang Yi1, Li Su-ming2, Yang Jian2   

  1. 1Department of Cardio-thoracic Surgery, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai  200233, China
    2Department of Materials Science, Fudan University, Shanghai  200235, China
  • Received:2010-12-02 Revised:2011-01-28 Online:2011-08-20 Published:2011-08-20
  • Contact: Lü Zhi-qian, Professor, Chief physician, Doctoral supervisor, Department of Cardio-thoracic Surgery, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai 200233, China luzhiqian@163.com
  • About author:Guo Qing-kui☆, Studying for doctorate, Attending physician, Department of Cardio-thoracic Surgery, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai 200233, China gqk1978@126.com
  • Supported by:

    the Science and Technology Commission Item of Shanghai, No. 074107061*

PDF

316

被引次数

8

摘要：

背景：目前应用于临床的金属裸支架、金属药物洗脱支架、合金支架等置入心血管后会导致局部血管内膜增生、血栓形成，增加心血管不良事件发生率。因此，应用高分子聚合物材料研发和制备完全生物可降解血管支架逐渐成为研究热点。
目的：观察新型完全生物可降解材料聚外消旋乳酸-三亚甲基碳酸酯(PDLLA/TMC)(50/50)聚合物在机体内的降解行为和组织相容性。 
方法：以课题组前期合成并研究的聚合物PDLLA/TMC(50/50)为实验对象，聚左旋乳酸-三亚甲基碳酸酯(PLLA/TMC)(50/50)和聚乳酸(PLLA)为对照，分别将其薄膜片植入144只6月龄Wistar大鼠，在不同的时间点，采用体积排除色谱、凝胶渗透色谱、核磁共振、环境扫描电镜研究其体内降解行为，并通过光镜下镜检及周围炎性细胞计数量化评价其组织相容性。
结果与结论：在植入机体前60 d，3组材料的失重率并没有太大的区别，降解速率均相对平稳缓慢，PDLLA/TMC的降解速率略快于其他两组聚合物材料，60 d后PDLLA/TMC的降解速率明显加快，其失重率显著高于另外两种聚合物材料，180 d后PDLLA/TMC大部分被降解，其余两种聚合物降解很少。3种聚合物材料包埋于生物体内即开始出现相对分子质量下降，初期下降速率较快，而后逐渐趋缓。3种材料的表面结构随着降解时间的延长，由初期的较为光滑整齐变为后期的皱褶、扭曲、紊乱、凹陷和孔洞，且PDLLA/TMC材料表面变化较明显。PDLLA/TMC和PLLA/TMC与PLLA比较，各个时间点均有相对较低的炎症细胞计数，差异均有显著性意义(P < 0.05)；而PDLLA/TMC与PLLA/TMC比较，各个时间节点上的炎性细胞计数差异均无显著性意义(P > 0.05)。证实PDLLA/TMC聚合物是一种新型的完全生物可降解材料，具有良好的降解性能和组织相容性。

关键词: 生物可降解, 聚合物, 血管内支架, 组织相容性, 聚外消旋乳酸-三亚甲基碳酸酯

Abstract:

BACKGROUND: Implantation of current used bare metal stent, metal drug-eluting stent, or alloy stent would result in local intimal hyperplasia, thrombosis and increase incidence of adverse cardiovascular event. Therefore, the development and preparation of high molecular polymer biodegradable stent has aroused increasing attention.
OBJECTIVE: To study the behavior and histocompatibility of novel fully biodegradable material of poly trimethylene carbonate-co-d, l-lactide (PDLLA/TMC) in vivo. 
METHODS: The early-stage synthetized materials of PDLLA/TMC (50/50) were used in the experiment group and the PLLA/TMC (50/50) and PLLA in the control. The patches of each kind of the three polymers above were implanted into the subcutaneous tissue of the 144 Wistar mouse with equal gender, six months old. The polymers patches and their surrounding tissues were taken out and weighed and sliced for hematoxylin-esoin staining at the phases of different test time. Their biodegradable behaviors    in vivo were tested by the methods of size exclusion chromatography (SEC), gel permeation chromatography (GPC), nuclear magnetic resonance (NMR) and environmental scanning electron microscope (ESEM), and their histocompatibility was evaluated by inflammation cells counting in quantity with light microscope.
RESULTS AND CONCLUSION: In the first 60 days of implantation, there was no significant difference in the percentage of mass loss among the three groups, and their velocity of degradation was relatively slow, though it was slightly faster in the PDLLA/TMC than in the PLLA/TMC and PLLA. During the 60 days to 180 days, PDLA/TMC degradation velocity accelerated obviously, and its percentage of mass loss was much higher than the other two polymers. At 180 days, most of the PDLLA/TMC degraded while the PLLA/TMC and PLLA degraded less. When the three polymers were implanted into the mouse body, at first their molecular declined rapidly, then the decline went into a slow stage gradually. With the time extended, their smooth and orderly superficial structure transformed into ruffle, twist, turbulent, full of hole and hollow, which was rather obvious in the polymer of PDLLA/TMC. Also, there were relative lower inflammation cells counting in the PDLLA/TMC and PLLA/TMC group at the phase of different test time, compared to the PLLA group the differences had statistic significance (P < 0.05), but there was no statistic significance between the PDLLA/TMC and PLLA/TMC group (P > 0.05). The polymer of PDLLA/TMC, which has favorable degradation performance and histocopatibility, is a novel fully biodegradable material and capable of manufacturing the implanted cardiovascular stent.

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