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聚(ω-甲氧基烷基丙烯酸酯):具有可调节蛋白质吸附性能的非血栓性聚合物家族。

Poly(ω-methoxyalkyl acrylate)s: Nonthrombogenic Polymer Family with Tunable Protein Adsorption.

机构信息

Institute for Materials Chemistry and Engineering, Kyushu University , CE41 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan.

Department of Biochemical Engineering, Graduate School of Science and Engineering, Yamagata University , 4-3-16 Jonan, Yonezawa, Yamagata 992-8510, Japan.

出版信息

Biomacromolecules. 2017 Dec 11;18(12):4214-4223. doi: 10.1021/acs.biomac.7b01247. Epub 2017 Nov 28.

Abstract

A series of polyacrylates with different n-alkyl side chain lengths (1 to 6, and 12 carbons) and a ω-methoxy terminal group (poly(ω-methoxyalkyl acrylate): PMCxA) were prepared to study their nonthrombogenicity using human platelet adhesion, micro bicinchoninic acid (micro BCA) protein assay, and enzyme-linked immunosorbent assay (ELISA) tests. In all cases, human platelet adhesion was suppressed on the PMCxA-coated substrates, and the number of human platelets adhered to the PMC3A (poly(3-methoxypropyl acrylate))-coated surface was comparable to that of commercialized nonthrombogenic coating agent poly(2-methoxyethyl acrylate) (PMEA, equal to PMC2A). The amount of protein adsorbed onto the PMCxA was investigated by micro BCA using bovine serum albumin (BSA) and human fibrinogen (hFbn), revealing that PMC3A exhibited significantly high resistance to nonspecific BSA adsorption. Additionally, the amount of hFbn adsorbed onto the PMC3A was suppressed to the same extent as PMEA. The exposure degree of platelet adhesion sites in adsorbed hFbn was evaluated using an ELISA test, and the degree on the PMCxA with three to six methylene carbons was comparable to the PMEA. The hydration water structure in the hydrated PMCxA was also characterized using differential scanning calorimetry (DSC). The amount of intermediate water, which is the hydration water molecules that moderately interact with the polymer matrix, was maximum in the PMEA with two methylene run lengths, whereas the amount decreased by increasing the number of methyelnes in the side chain. The amount of adsorbed protein increased with a decrease in the amount of intermediate water, suggesting that the protein adsorption amount is tunable by simply changing the number of methylene carbons in the side chain. The present study revealed that poly(ω-methoxyalkyl acrylate)s are useful for blood-contacting medical devices, and PMC3A is the best mode of PMCxA to apply as an antiprotein adsorption coating agent.

摘要

一系列具有不同 n-烷基侧链长度(1 至 6 个和 12 个碳原子)和 ω-甲氧基端基的聚丙烯酸酯(聚(ω-甲氧基烷基丙烯酸酯):PMCxA)被制备出来,以使用人血小板黏附、微量双缩脲(micro BCA)蛋白测定和酶联免疫吸附测定(ELISA)试验来研究它们的抗血栓性。在所有情况下,人血小板在 PMCxA 涂层基底上的黏附均受到抑制,并且黏附在 PMC3A(聚(3-甲氧基丙基丙烯酸酯))涂层表面上的人血小板数量与商业化的非血栓形成涂层剂聚(2-甲氧基乙基丙烯酸酯)(PMEA,相当于 PMC2A)相当。通过使用牛血清白蛋白(BSA)和人纤维蛋白原(hFbn)的微量 BCA 研究吸附到 PMCxA 上的蛋白质量,发现 PMC3A 表现出对非特异性 BSA 吸附的显著高抵抗力。此外,吸附到 PMC3A 上的 hFbn 量也被抑制到与 PMEA 相同的程度。使用 ELISA 试验评估吸附的 hFbn 中血小板黏附部位的暴露程度,并且在具有三个至六个亚甲基的 PMCxA 上的暴露程度与 PMEA 相当。使用差示扫描量热法(DSC)还对水合 PMCxA 中的水合水结构进行了表征。中等程度与聚合物基质相互作用的水化水分子的中间水量在具有两个亚甲基长度的 PMEA 中达到最大值,而随着侧链中亚甲基数量的增加,中间水量减少。吸附蛋白的量随着中间水量的减少而增加,这表明通过简单地改变侧链中的亚甲基碳原子数,可调节蛋白质的吸附量。本研究表明,聚(ω-甲氧基烷基丙烯酸酯)可用于与血液接触的医疗器械,并且 PMC3A 是作为抗蛋白质吸附涂层剂应用的 PMCxA 的最佳模式。

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