IMMOBILIZATION OF POLY(ETHYLENE GLYCOL) ONTO A POLY(VINYL ALCOHOL) HYDROGEL .2. EVALUATION OF THROMBOGENICITY

IMMOBILIZATION OF POLY(ETHYLENE GLYCOL) ONTO A POLY(VINYL ALCOHOL) HYDROGEL .2. EVALUATION OF THROMBOGENICITY
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DOI:
10.1002/jbm.820271105
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发表时间:
1993-11-01
期刊:
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH
影响因子:
--
通讯作者:
SEFTON, MV
SEFTON, MV
中科院分区:
其他
文献类型:
--
作者:
LLANOS, GR;SEFTON, MV

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固定化聚乙二醇(PEG)减少了聚乙烯醇(PVA)水凝胶吸附牛血清白蛋白(BSA)的量,但不降低水凝胶表面的血小板反应性。PEG,分子量(MW)2000或5000,具有或不具有单甲氧基端基,通过环状缩醛或氨基甲酸酯官能团与戊二醛交联的PVA共价结合,表面覆盖率为70%(通过X射线光电子能谱[XPS]测量)。通过环状缩醛固定单甲氧基-PEG将BSA对PVA的吸附从11 +/- 2 nmol/m2分别减少到3.9 +/- 0.3 nmol/m2和3.3 +/- 0.3 nmol/m2(MW 2000和5000)。类似地,氨基甲酸酯结合的PEG将吸附降低至3.5 +/- 1.6 nmol/m2(对于MW 2000)和5.4 +/- 1.0 nmol/m2(对于MW 5000)。PVA的全血凝固时间(使用钱德勒环)不受共价连接的PEG的影响,尽管使用荧光底物测量的表面处凝血酶产生的初始速率略微降低;与PVA的5.6 +/-1.0cm/sec相比,MW 2000和5000分别获得4.2 +/-0.1cm/sec和3.5 +/-0.1cm/sec的速率常数。使用犬动静脉分流的离体评价显示,在4天后,具有或不具有结合PEG的水凝胶使循环血小板水平降低35-70%。血小板环氧合酶活性测定的血小板破坏的初始分数率,表明环缩醛或氨基甲酸酯结合的PEG的分子量对PVA产生的血小板消耗没有影响。根据这些结果,可能需要进一步评价PEG假说,至少是因为它与血小板相互作用有关。 (C)John Wiley & Sons,Inc.
Immobilized polyethylene glycol (PEG) reduced the amount of bovine serum albumin (BSA) adsorbed on polyvinyl alcohol (PVA) hydrogel, but did not reduce the platelet reactivity of the hydrogel surface. PEG, molecular weight (MW) 2000 or 5000, with or without a monomethoxy end group, was covalently bound to glutaraldehyde-crosslinked PVA either through a cyclic acetal or an urethane functional group with a surface coverage of 70% (as measured by x-ray photoelectron spectroscopy [XPS]). Immobilization of monomethoxy-PEG via a cyclic acetal reduced BSA adsorption to PVA from 11 +/- 2 nmol/m2 to 3.9 +/- 0.3 nmol/m2 and 3.3 +/- 0.3 nmol/m2 for MW 2000 and 5000, respectively. Similarly, urethane bound PEG reduced adsorption to 3.5 +/- 1.6 nmol/m2 for MW 2000 and 5.4 +/- 1.0 nmol/m2 for MW 5000. Whole blood clotting times of PVA (using a Chandler loop) were not affected by covalently linked PEG, although the initial rate of thrombin generation at the surface, measured using a fluorogenic substrate, was marginally reduced; a rate constant of 4.2 +/- 0.1 cm/sec and 3.5 +/- 0.1 cm/sec were obtained for MW 2000 and 5000, respectively, compared to 5.6 +/- 1.0 cm/sec for PVA. Ex vivo evaluation using a canine arteriovenous shunt revealed that the hydrogel, with or without bound PEG, reduced circulating platelet levels by 35-70% after 4 days. The initial fractional rate of platelet destruction determined from measurement of platelet cyclooxygenase activity, indicated that cyclic acetal or urethane bound PEG of either molecular weight had no effect on platelet consumption produced by PVA. The PEG hypothesis at least as it relates to platelet interactions may need to be evaluated further in the light of these results. (C) 1993 John Wiley & Sons, Inc.