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肝素-阿司匹林复合改性小口径 PCL/PU 血管移植物预防急性血栓形成。

Small-diameter PCL/PU vascular graft modified with heparin-aspirin compound for preventing the occurrence of acute thrombosis.

机构信息

Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.

Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, PR China; CAS Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, PR China.

出版信息

Int J Biol Macromol. 2023 Sep 30;249:126058. doi: 10.1016/j.ijbiomac.2023.126058. Epub 2023 Jul 29.

Abstract

The occurrence of acute thrombosis, directly related to platelet aggregation and coagulant system, is a considerable reason for the failure of small-diameter vascular grafts. Heparin is commonly used as a functional molecule for graft modification due to the strong anticoagulant effect. Unfortunately, heparin cannot directly resist the adhesion and aggregation of platelets. Therefore, we have prepared a heparin-aspirin compound by coupling heparin with aspirin, an antiplatelet drug, and covalently grafted it onto the surface of polycaprolactone/polyurethane composite tube. In this way, the graft not only showed a dual function of both anticoagulation and antiplatelet, but also effectively avoided the rapid drug release and excessive toxicity to other organs caused by simple blending the medicine with material matrix. The compound retained the original function of heparin, showing good hydrophilicity and biocompatibility, which could promote the adhesion and proliferation of endothelial cells (ECs) and facilitate the process of tissue regeneration. What's more, the compound showed more effective than heparin in reducing platelet activation and preventing thrombosis. The graft modified by this compound maintained completely unobstructed for one month of implantation, while severe obstruction or stenosis occurred in PCL/PU and PCL/PU-Hep lumen at the first week, verifying the effect of the compound on preventing acute thrombosis. In general, this study proposed a designing method for small-diameter vascular graft which could prevent acute thrombosis and promote intimal construction.

摘要

急性血栓的发生与血小板聚集和凝血系统直接相关,是小直径血管移植物失效的一个重要原因。肝素由于具有很强的抗凝作用,通常被用作移植物修饰的功能分子。然而,肝素并不能直接抵抗血小板的黏附和聚集。因此,我们通过将肝素与抗血小板药物阿司匹林偶联,制备了肝素-阿司匹林化合物,并将其共价接枝到聚己内酯/聚氨基甲酸酯复合管的表面。这样,接枝不仅表现出抗凝和抗血小板的双重功能,而且有效地避免了药物与材料基质简单混合所导致的快速药物释放和对其他器官的过度毒性。该化合物保留了肝素的原有功能,表现出良好的亲水性和生物相容性,能够促进内皮细胞(ECs)的黏附和增殖,促进组织再生。此外,该化合物在减少血小板激活和预防血栓形成方面比肝素更有效。用该化合物修饰的移植物在植入后一个月内保持完全通畅,而在 PCL/PU 和 PCL/PU-Hep 管腔中,在第一周就出现了严重的阻塞或狭窄,验证了该化合物在预防急性血栓形成方面的效果。总的来说,本研究提出了一种预防急性血栓形成和促进内膜构建的小直径血管移植物设计方法。

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