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受贻贝启发的肝素固定化纤维素凝胶珠用于从全血中选择性去除低密度脂蛋白

A mussel-inspired approach towards heparin-immobilized cellulose gel beads for selective removal of low density lipoprotein from whole blood.

机构信息

Department of Nephrology, West China Hospital of Sichuan University, Chengdu, 610041, China.

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

出版信息

Carbohydr Polym. 2018 Dec 15;202:116-124. doi: 10.1016/j.carbpol.2018.08.118. Epub 2018 Aug 29.

Abstract

In this study, we report a mussel-inspired approach to fabricate heparin-immobilized cellulose (HeTaCe) gel beads with self-anticoagulative and biocompatible properties which can selectively remove low density lipoprotein (LDL) from whole blood directly. First, a phase inversion technique was applied to prepare cellulose gel beads. Then the as-prepared gel beads were dipped into a mixed solution of heparin and tannic acid in phosphate buffered saline (PBS, pH 8.5) to obtain HeTaCe gel beads. Blood compatibility experiments indicated that the HeTaCe gel beads could suppress complement activation as well as contact activation and prolong the clotting times to the upper detect limits (activated partial thromboplastin time >600 s and thrombin time >180 s) of the automated blood coagulation analyzer. An ideal adsorption capacity of LDL in vitro was achieved by the HeTaCe gel beads with an amount of 79.1 mg/g. Besides, dynamic column adsorption test further demonstrated a selective adsorption of LDL without a significant reduction of high density lipoprotein (HDL) in a simulative hemoperfusion system. It is believed that the HeTaCe gel beads will be quite appealing to future clinical practice aiming at lowering LDL and improving the outcomes of patients with high cardiovascular risk.

摘要

在这项研究中,我们报告了一种受贻贝启发的方法,制备具有自抗凝和生物相容性的肝素固定化纤维素(HeTaCe)凝胶珠,可直接从全血中选择性去除低密度脂蛋白(LDL)。首先,采用相转化技术制备纤维素凝胶珠。然后,将所得凝胶珠浸入肝素和鞣酸在磷酸盐缓冲盐水(PBS,pH8.5)中的混合溶液中,得到 HeTaCe 凝胶珠。血液相容性实验表明,HeTaCe 凝胶珠可以抑制补体激活和接触激活,并将凝固时间延长至自动血液凝固分析仪的上限(活化部分凝血活酶时间>600s 和凝血酶时间>180s)。HeTaCe 凝胶珠在体外具有 79.1mg/g 的 LDL 理想吸附容量。此外,动态柱吸附试验进一步证明了 LDL 的选择性吸附,而在模拟血液灌流系统中高密度脂蛋白(HDL)没有明显减少。我们相信,HeTaCe 凝胶珠在未来的临床实践中具有很大的吸引力,旨在降低 LDL 并改善高心血管风险患者的预后。

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