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由 1,3-三亚甲基碳酸酯、丙交酯和己内酯制备的生物可吸收均聚物和共聚物的血液相容性和细胞相容性。

Haemo- and cytocompatibility of bioresorbable homo- and copolymers prepared from 1,3-trimethylene carbonate, lactides, and epsilon-caprolactone.

机构信息

Department of Materials Science, Fudan University, Shanghai 200433, China.

出版信息

J Biomed Mater Res A. 2010 Aug;94(2):396-407. doi: 10.1002/jbm.a.32677.

DOI:10.1002/jbm.a.32677
PMID:20186738
Abstract

A series of bioresorbable polymers were prepared by ring-opening polymerization of L-lactide (LLA), DL-lactide (DLLA), epsilon-caprolactone (CL) and 1,3-trimethylene carbonate (TMC), using low toxic zinc lactate as catalyst. The various PLLA, PTMC, PCL homopolymers, and PLLA-TMC, PDLLA-TMC, PCL-TMC copolymers with 50/50 molar ratios were characterized by using analytical techniques such as proton nuclear magnetic resonance, gel permeation chromatography, tensiometer, and differential scanning calorimetry. The haemo- and cyto-compatibility were investigated in order to evaluate the potential of the polymers as coating material in drug eluting stents. Haemolysis tests show that all the homo- and copolymers present very low haemolytic ratios, indicating good haemolytic properties. Adhesion and activation of platelets were observed on the surface of PLLA, PCL, PLLA-TMC, and PDLLA-TMC films, while less platelets and lower activation were found on PTMC. The most interesting results were obtained with PCL-TMC which exhibited the lowest degree of activation with few adhered platelets, in agreement with its outstanding anticoagulant properties. Both indirect and direct cytocompatibility studies were performed on the polymers. The relative growth ratio data obtained from the liquid extracts during the 6-day cell culture period indicate that all the polymers present very low cytotoxicity. Microscopic observations demonstrate adhesion, spreading and proliferation of human umbilical vein endothelial cells ECV304. Therefore, it is concluded that these bioresorbable polymers, in particular PCL-TMC, are promising candidate materials as drug loading coating material in drug eluting stents.

摘要

一系列可生物降解聚合物是通过 L-丙交酯(LLA)、DL-丙交酯(DLLA)、ε-己内酯(CL)和 1,3-三亚甲基碳酸酯(TMC)的开环聚合,使用低毒乳酸锌作为催化剂制备的。通过质子核磁共振、凝胶渗透色谱、张力仪和差示扫描量热法等分析技术对各种 PLLA、PTMC、PCL 均聚物以及摩尔比为 50/50 的 PLLA-TMC、PDLLA-TMC、PCL-TMC 共聚物进行了表征。为了评估聚合物作为药物洗脱支架涂层材料的潜力,对其血液相容性和细胞相容性进行了研究。溶血试验表明,所有的均聚物和共聚物的溶血率都非常低,表明溶血性能良好。在 PLLA、PCL、PLLA-TMC 和 PDLLA-TMC 薄膜表面观察到血小板的黏附和活化,而在 PTMC 表面发现的血小板较少且活化程度较低。最有趣的结果是在 PCL-TMC 上获得的,其具有最低的活化程度和少量黏附的血小板,这与其出色的抗凝性能一致。对聚合物进行了间接和直接细胞相容性研究。在 6 天细胞培养期间从液体提取物中获得的相对生长比数据表明,所有聚合物的细胞毒性都非常低。显微镜观察表明,人脐静脉内皮细胞 ECV304 黏附、铺展和增殖。因此,可以得出结论,这些可生物降解聚合物,特别是 PCL-TMC,是作为药物洗脱支架药物负载涂层的有前途的候选材料。

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