Molecular barriers to biomaterial thrombosis by modification of surface proteins with polyethylene glycol

Molecular barriers to biomaterial thrombosis by modification of surface proteins with polyethylene glycol
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DOI:
10.1016/s0142-9612(98)00098-2
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发表时间:
1998-10-01
期刊:
影响因子:
14
通讯作者:
Wagner, WR
Wagner, WR
中科院分区:
工程技术1区
文献类型:
--
作者:
Deible, CR;Petrosko, P;Wagner, WR

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对于心血管生物材料,血栓形成、血栓栓塞和血管移植闭塞被认为是由含有血小板粘附配体的蛋白质的吸附引起的。聚乙二醇二异氰酸酯(PEG-二异氰酸酯,3400 MW)可能与蛋白质胺发生反应,在生物材料上吸附的蛋白质上形成分子屏障,从而掩盖粘附配体并防止急性表面血栓形成。为了测试这一概念,PE、PTFE 和玻璃微导管预先吸附有纤维蛋白原,并用 PEG-二异氰酸酯、非反应性 PEG-二羟基进行处理,或保持不处理。将 In-111 标记的血小板在人全血中灌注 1 分钟(壁剪切速率 = 312 s(-1))后,经过 PEG-二异氰酸酯处理的表面比未处理的表面减少了 96%(PE)、97%(PTFE)和 94%(玻璃)的血小板沉积。与 PEG-二羟基处理相比,PEG-二异氰酸酯处理也出现类似的减少。血液接触前 1 小时低剪切血浆灌注不会降低 PEG-二异氰酸酯的抑制作用。 PEG-二异氰酸酯处理也减少了血小板在胶原涂层玻璃盖玻片上的粘附和血小板在预凝涤纶上的沉积(分别为 93% 和 91%)。因此,蛋白质反应性 PEG 可用于在表面相关蛋白质上形成分子屏障,以抑制心血管生物材料上的急性血栓形成。 (C) 1998 年由爱思唯尔科学有限公司出版。保留所有权利。
For cardiovascular biomaterials, thrombosis, thromboembolism and vascular graft occlusion are believed to be precipitated by the adsorption of proteins containing adhesive ligands for platelets. Polyethylene-glycol-diisocyanate (PEG-diisocyanate, 3400 MW) may potentially react with protein amines to form molecular barriers on adsorbed proteins on biomaterials, thereby masking adhesive ligands and preventing acute surface thrombosis. To test this notion, PE, PTFE, and glass microconduits were pre-adsorbed with fibrinogen and treated with PEG-diisocyanate, non-reactive PEG-dihydroxyl, or remained untreated. Following perfusion of In-111-labeled platelets in whole human blood for 1 min (wall shear rate = 312 s(-1)), PEG-diisocyanate treated surfaces experienced 96% (PE), 97% (PTFE) and 94% (glass) less platelet deposition than untreated surfaces. Similar reductions were seen for PEG-diisocyanate versus PEG-dihydroxyl treatment. Low shear perfusions of plasma for 1 h prior to blood contact did not reduce the inhibitory effect of PEG-diisocyanate. Platelet adhesion onto collagen-coated glass coverslips and platelet deposition onto preclotted Dacron were also reduced by treatment with PEG-diisocyanate(93 and 91%, respectively). Protein-reactive PEG may thus have utility in forming molecular barriers on surface-associated proteins to inhibit acute thrombosis on cardiovascular biomaterials. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.