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载没食子儿茶素没食子酸酯夹层层层功能化的聚己内酯血管移植物用于增强抗血栓形成和抗炎作用。

Polycaprolactone vascular graft with epigallocatechin gallate embedded sandwiched layer-by-layer functionalization for enhanced antithrombogenicity and anti-inflammation.

机构信息

National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan 610065, China.

National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan 610065, China.

出版信息

J Control Release. 2020 Apr 10;320:226-238. doi: 10.1016/j.jconrel.2020.01.043. Epub 2020 Jan 23.

DOI:10.1016/j.jconrel.2020.01.043
PMID:31982435
Abstract

Small-diameter artificial vascular grafts modified with layer-by-layer (LBL) coating show promise in reducing the failure caused by thrombosis and inflammation, but undesirable stability and bioactivity issues of the coating and payload usually limits their long-term efficacy. Herein, inspired by catechol/gallol surface chemistry, a sandwiched layer-by-layer coating constructed by polyethyleneimine (PEI) and heparin with the embedding of epigallocatechin gallate (EGCG)-dexamethasone combination was used to modify the electrospun polycaprolactone (PCL) vascular grafts. Polyphenol embedding endowed the coating with abundant intermolecular interactions between each coating components, mainly contributed by the π-π stacking, weak intermolecular cross-linking and enriched hydrogen bonding, which further enhanced the coating stability and also supported the sustained release of the payloads, like polyelectrolytes and drugs. Compared with the conventional LBL coating, the loading amounts of heparin and dexamethasone in the EGCG embedded LBL coatings doubled and the drug release could be significantly prolonged without serious initial burst. The in vitro and ex vivo assays indicated that the modified PCL vascular grafts would address impressive prolonged anti-platelet adhesion/activation and anti-fibrinogen denaturation ability. Meanwhile, the dexamethasone loading entrusted the sandwiched LBL coating with mild tissue response, in terms of inhibiting the macrophage activation. These results strongly demonstrated that the sandwiched LBL coating with EGCG embedding was an effective method to improve the patency rates of PCL small artificial vascular grafts, which could also be extended to other blood-contacting materials.

摘要

采用层层(LBL)涂层修饰小直径人工血管移植物,有望降低血栓和炎症引起的失效,但涂层和载药的不理想稳定性和生物活性问题通常限制了其长期疗效。受儿茶酚/没食子酸表面化学的启发,本文使用聚乙烯亚胺(PEI)和肝素构建夹层 LBL 涂层,并嵌入表没食子儿茶素没食子酸酯(EGCG)-地塞米松复合物,来修饰静电纺丝聚己内酯(PCL)血管移植物。多酚嵌入赋予了涂层各涂层成分之间丰富的分子间相互作用,主要归因于π-π堆积、弱分子间交联和丰富的氢键,这进一步增强了涂层的稳定性,同时支持了载药的持续释放,如聚电解质和药物。与传统的 LBL 涂层相比,EGCG 嵌入 LBL 涂层中肝素和地塞米松的载药量增加了一倍,药物释放可以显著延长,而没有严重的初始突释。体外和体内实验表明,修饰后的 PCL 血管移植物具有显著延长抗血小板黏附/激活和抗纤维蛋白原变性能力。同时,地塞米松的负载赋予夹层 LBL 涂层以温和的组织反应,抑制巨噬细胞的激活。这些结果有力地证明了 EGCG 嵌入的夹层 LBL 涂层是提高 PCL 小口径人工血管移植物通畅率的有效方法,该方法也可扩展到其他与血液接触的材料。

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