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通过基于环糊精的超分子的层层组装在聚合物膜上形成肝素模拟多层涂层。

Heparin-mimicking multilayer coating on polymeric membrane via LbL assembly of cyclodextrin-based supramolecules.

机构信息

College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University , Chengdu 610065, China.

出版信息

ACS Appl Mater Interfaces. 2014 Dec 10;6(23):21603-14. doi: 10.1021/am506249r. Epub 2014 Nov 19.

Abstract

In this study, multifunctional and heparin-mimicking star-shaped supramolecules-deposited 3D porous multilayer films with improved biocompatibility were fabricated via a layer-by-layer (LbL) self-assembly method on polymeric membrane substrates. Star-shaped heparin-mimicking polyanions (including poly(styrenesulfonate-co-sodium acrylate; Star-PSS-AANa) and poly(styrenesulfonate-co-poly(ethylene glycol)methyl ether methacrylate; Star-PSS-EGMA)) and polycations (poly(methyl chloride-quaternized 2-(dimethylamino)ethyl methacrylate; Star-PMeDMA) were first synthesized by atom transfer radical polymerization (ATRP) from β-cyclodextrin (β-CD) based cores. Then assembly of 3D porous multilayers onto polymeric membrane surfaces was carried out by alternating deposition of the polyanions and polycations via electrostatic interaction. The surface morphology and composition, water contact angle, blood activation, and thrombotic potential as well as cell viability for the coated heparin-mimicking films were systematically investigated. The results of surface ATR-FTIR spectra and XPS spectra verified successful deposition of the star-shaped supramolecules onto the biomedical membrane surfaces; scanning electron microscopy (SEM) and atomic force microscopy (AFM) observations revealed that the modified substrate had 3D porous surface morphology, which might have a great biological influence on the biointerface. Furthermore, systematic in vitro investigation of protein adsorption, platelet adhesion, human platelet factor 4 (PF4, indicates platelet activation), activate partial thromboplastin time (APTT), thrombin time (TT), coagulation activation (thrombin-antithrombin III complex (TAT, indicates blood coagulant)), and blood-related complement activation (C3a and C5a, indicates inflammation potential) confirmed that the heparin-mimicking multilayer coated membranes exhibited ultralow blood component activations and excellent hemocompatibility. Meanwhile, after surface coating, endothelial cell viability was also promoted, which indicated that the heparin-mimicking multilayer coating might extend the application fields of polymeric membranes in biomedical fields.

摘要

在这项研究中,通过层层(LbL)自组装方法,在聚合物膜基底上制备了多功能且具有肝素模拟作用的星形超分子沉积 3D 多孔多层膜,提高了生物相容性。星形肝素模拟聚阴离子(包括聚(苯乙烯磺酸盐-co-丙烯酸钠;Star-PSS-AANa)和聚(苯乙烯磺酸盐-co-聚(乙二醇)甲醚甲基丙烯酸酯;Star-PSS-EGMA)和聚阳离子(聚(氯甲基季铵化 2-(二甲氨基)乙基甲基丙烯酸酯;Star-PMeDMA))首先通过原子转移自由基聚合(ATRP)从β-环糊精(β-CD)为核心合成。然后,通过静电相互作用交替沉积聚阴离子和聚阳离子,将 3D 多孔多层膜组装到聚合物膜表面上。系统研究了涂层肝素模拟膜的表面形态和组成、水接触角、血液激活、血栓形成潜力以及细胞活力。表面 ATR-FTIR 光谱和 XPS 光谱的结果证明了星形超分子成功沉积在生物医学膜表面上;扫描电子显微镜(SEM)和原子力显微镜(AFM)观察表明,修饰后的基底具有 3D 多孔表面形态,这可能对生物界面产生很大的生物学影响。此外,系统的体外蛋白质吸附、血小板黏附、人血小板因子 4(PF4,表明血小板激活)、激活部分凝血活酶时间(APTT)、凝血酶时间(TT)、凝血激活(凝血酶-抗凝血酶 III 复合物(TAT,表明凝血剂))和血液相关补体激活(C3a 和 C5a,表明炎症潜力)的研究证实,肝素模拟多层涂层膜表现出超低的血液成分激活和优异的血液相容性。同时,表面涂层后,内皮细胞活力也得到了促进,这表明肝素模拟多层涂层可能扩展聚合物膜在生物医学领域的应用领域。

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