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中心静脉导管蛋白吸附与水灌注表面保护机制之间的关系

Relationship Between Central Venous Catheter Protein Adsorption and Water Infused Surface Protection Mechanisms.

作者信息

Sutherland David W, Blanks Zachary D, Zhang Xin, Charest Joseph L

机构信息

Department of Mechanical Engineering, Boston University, Boston, MA, USA.

Biomedical Microsystems, Draper, Cambridge, MA, USA.

出版信息

Artif Organs. 2018 Nov;42(11):E369-E379. doi: 10.1111/aor.13274. Epub 2018 Aug 23.

Abstract

Central venous catheters (CVCs) are implanted in the majority of dialysis patients despite increased patient risk due to thrombotic occlusion and biofilm formation. Current solutions remain ineffective at preventing these complications and treatment options are limited and often harmful. We present further analysis of the previously proposed water infused surface protection (WISP) technology, an active method to reduce protein adsorption and effectively disrupt adsorbed protein sheaths on the inner surface of CVCs. A WISP CVC is modeled by a hollow fiber membrane (HFM) in a benchtop device which continuously infuses a saline solution across the membrane wall into the blood flow, creating a blood-free boundary layer at the lumen surface. Total protein adsorption is measured under various experimental conditions to further test WISP performance. The WISP device shows reduced protein adsorption as blood and WISP flow rates increase (P < 0.040) with up to a 96% reduction in adsorption over the no WISP condition. When heparin is added to the WISP flow, protein adsorption (0.097[+0.035/-0.055] µg/mm ) is reduced when compared to both bolus administration and nondoped WISP, 0.406(+0.056/-0.065) µg/mm (P = 0.001) and 0.191 (+0.076/-0.126) (P = 0.029), respectively. Additionally, when heparinized WISP is applied to a preadsorbed protein layer, 0.375(+0.114/-0.164) µg/mm , it displays the ability to reduce the previously-adsorbed protein, 0.186(+0.058/-0.084) µg/mm (P = 0.0012), suggesting aptitude for intermittent treatments. The WISP technology not only shows the ability to reduce protein adsorption, but also the ability to remove preadsorbed material by effectively delivering drugs to the point of adsorption; functionalities that could greatly improve clinical outcomes.

摘要

尽管由于血栓形成闭塞和生物膜形成会增加患者风险,但大多数透析患者仍植入了中心静脉导管(CVC)。目前的解决方案在预防这些并发症方面仍然无效,治疗选择有限且往往有害。我们对先前提出的注水表面保护(WISP)技术进行了进一步分析,这是一种减少蛋白质吸附并有效破坏CVC内表面吸附蛋白鞘的主动方法。在台式设备中,用中空纤维膜(HFM)对WISP CVC进行建模,该设备将盐溶液持续穿过膜壁注入血流中,在管腔表面形成无血边界层。在各种实验条件下测量总蛋白质吸附,以进一步测试WISP性能。随着血液和WISP流速增加,WISP装置显示出蛋白质吸附减少(P < 0.040),与无WISP条件相比,吸附减少高达96%。当向WISP流中添加肝素时,与推注给药和未掺杂WISP相比,蛋白质吸附(0.097[+0.035/-0.055]μg/mm)降低,分别为0.406(+0.056/-0.065)μg/mm(P = 0.001)和0.191(+0.076/-0.126)(P = 0.029)。此外,当将肝素化WISP应用于预吸附的蛋白质层(0.375[+0.114/-0.164]μg/mm)时,它显示出减少先前吸附蛋白质的能力,为0.186(+0.058/-0.084)μg/mm(P = 0.0012),表明适用于间歇性治疗。WISP技术不仅显示出减少蛋白质吸附的能力,还显示出通过有效地将药物输送到吸附点来去除预吸附物质的能力;这些功能可以大大改善临床结果。

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