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将阿加曲班和 mPEG-NH 固定在聚醚砜膜表面,制备有效的抗血栓生物界面。

Immobilizing argatroban and mPEG-NH on a polyethersulfone membrane surface to prepare an effective nonthrombogenic biointerface.

机构信息

a Department of Nephrology , Xiangya Hospital of Central South University , Changsha , Hunan , China.

出版信息

J Biomater Sci Polym Ed. 2019 Jun;30(8):608-628. doi: 10.1080/09205063.2019.1595891. Epub 2019 Apr 4.

Abstract

Systemic anticoagulation is not suitable for hemodialysis (HD) patients with a high risk of bleeding in the clinic. An HD membrane that provides a localized anticoagulation membrane surface may be a promising strategy to solve this intractable problem for HD patients. Herein, we modified a nonthrombogenic polyethersulfone (PES) dialyzer membrane by grafting argatroban (AG) and methoxy polyethylene glycol amine (mPEG-NH) via a polydopamine (PDA) strategy. The PES substrates were immersed in an alkaline dopamine solution for 24 h, and then, AG and mPEG-NH were sequentially grafted covalently onto the resultant membrane. Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy (XPS) were utilized to confirm the successful introduction of PDA and the immobilization of AG and mPEG-NH. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) were used to observe the surface structure and morphology after the surface modification. The excellent antithrombotic abilities of the modified membrane were demonstrated by the suppression of platelet adhesion and activation, prolongation of clotting times, and inhibition of thrombin generation and complement activation. This work describes an efficient and convenient method to immobilize AG and mPEG-NH to create a nonthrombogenic biointerface for blood-contacting devices such as HD membranes.

摘要

在临床中,对于存在高出血风险的血液透析(HD)患者,全身抗凝并不适用。一种能够提供局部抗凝膜表面的 HD 膜可能是解决 HD 患者这一棘手问题的有前景的策略。在此,我们通过多巴胺(PDA)策略将精氨酸加压素(AG)和甲氧基聚乙二醇胺(mPEG-NH)接枝到非血栓性聚醚砜(PES)透析器膜上来对其进行修饰。PES 基底在碱性多巴胺溶液中浸泡 24 小时,然后将 AG 和 mPEG-NH 依次通过共价键接枝到所得膜上。衰减全反射-傅里叶变换红外光谱(ATR-FTIR)和 X 射线光电子能谱(XPS)用于确认 PDA 的成功引入和 AG 和 mPEG-NH 的固定。扫描电子显微镜(SEM)和原子力显微镜(AFM)用于观察表面改性后的表面结构和形态。修饰膜具有出色的抗血栓形成能力,表现为抑制血小板黏附与激活、延长凝血时间、抑制凝血酶生成和补体激活。本工作描述了一种有效且方便的方法,用于将 AG 和 mPEG-NH 固定到用于血液接触设备(如 HD 膜)的非血栓性生物界面上。

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