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Polycaprolactone vascular graft with epigallocatechin gallate embedded sandwiched layer-by-layer functionalization for enhanced antithrombogenicity and anti-inflammation.
Journal of Controlled Release ( IF 10.5 ) Pub Date : 2020-01-23 , DOI: 10.1016/j.jconrel.2020.01.043
Yanan Wang 1 , Boxuan Ma 1 , Anlin Yin 1 , Bo Zhang 1 , Rifang Luo 1 , Junqiang Pan 2 , Yunbing Wang 1
Affiliation  

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.

中文翻译:

具有表没食子儿茶素没食子酸酯的聚己内酯血管移植物嵌入了一层层的夹层功能,以增强抗血栓形成性和抗炎性。

经层层(LBL)涂层修饰的小直径人工血管移植物有望减少由血栓形成和炎症引起的衰竭,但是涂层和有效载荷的不希望的稳定性和生物活性问题通常会限制其长期功效。在此,受儿茶酚/胆甾醇表面化学的启发,使用由聚乙烯亚胺(PEI)和肝素制成的夹层逐层涂层,并嵌入表没食子儿茶素没食子酸酯(EGCG)-地塞米松组合物来修饰电纺聚己内酯(PCL)血管移植物。多酚包埋使涂层在各涂层组分之间具有丰富的分子间相互作用,这主要是由于π-π堆积,弱的分子间交联和富集的氢键所致;这进一步提高了涂层的稳定性,还支持了有效载荷的持续释放,例如聚电解质和药物。与传统的LBL涂层相比,EGCG包埋的LBL涂层中肝素和地塞米松的负载量增加了一倍,并且药物释放可以显着延长,而不会出现严重的初期破裂。体外和离体试验表明,修饰的PCL血管移植物将解决令人印象深刻的延长的抗血小板粘附/激活和抗纤维蛋白原变性的能力。同时,就抑制巨噬细胞活化而言,地塞米松负载赋予夹层的LBL涂层温和的组织反应。
更新日期:2020-01-23
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