National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University , Nanjing, 210023, P.R. China.
Department of Vascular Surgery, Nanjing Drum Tower Hospital, The Affliated Hospital of Nanjing University Medical School , Nanjing, 210008, P.R. China.
Langmuir. 2017 Nov 21;33(46):13430-13437. doi: 10.1021/acs.langmuir.7b03064. Epub 2017 Nov 8.
A new strategy for preparation of blood-contact materials, with their short-term anticoagulation depending on zwitterionic structure and long-term hemocompatibility based on endothelialization, was proposed, performed, and proved. The copolymer made of sulfonamide zwitterionic and acrylic acid was designed and synthesized, and grafted to the surface of the bare metal coronary stent. Then, the vascular endothelial cadherin (VE-Cad), one of the specific antibodies of endothelial progenitor cells (EPCs), was fixed onto the copolymer chain. Finally, it is proved by in vitro blood tests that the coronary stent decorated with VE-Cad loaded-amphoteric copolymer displayed good platelet anti-adhesion characteristic. This anti-adhesion characteristic was attributed to the zwitterionic structure and the biofunctionality of specifically capturing EPCs confirmed by the results that the antibody-decorated coronary stent was trapped with EPCs. Finally, the in vivo implantation experiments of the antibody-decorated coronary stent in rabbit for 4 weeks were carried out. Results indicated that the endothelium and smooth surface of the antibody-loaded stent was found to be due to the covered effect of EPCs, without obvious intimal hyperplasia. The strategy we proposed has great potential in the design and preparation of blood-contact biomedical materials and devices.
提出了一种新的血液接触材料制备策略，其短期抗凝作用依赖于两性离子结构，长期的血液相容性则基于内皮化。该策略已经被设计、执行并验证。设计并合成了由磺酸甜菜碱两性离子和丙烯酸组成的共聚物，并将其接枝到裸金属冠状动脉支架的表面。然后，将血管内皮钙黏蛋白（VE-Cad），一种内皮祖细胞（EPC）的特异性抗体，固定在共聚物链上。最后，通过体外血液测试证明，负载 VE-Cad 的两性离子共聚物修饰的冠状动脉支架具有良好的血小板抗黏附特性。这种抗黏附特性归因于两性离子结构和通过结果证实的特异性捕获 EPC 的生物功能，即抗体修饰的冠状动脉支架被 EPC 捕获。最后，对抗体修饰的冠状动脉支架在兔体内植入 4 周进行了体内植入实验。结果表明，由于 EPC 的覆盖作用，发现载抗体支架的内皮和光滑表面没有明显的内膜增生。我们提出的策略在血液接触生物医学材料和装置的设计和制备方面具有巨大的潜力。
