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用于肾脏替代治疗的平行板配置硅纳米孔膜的初步扩散清除率

Preliminary Diffusive Clearance of Silicon Nanopore Membranes in a Parallel Plate Configuration for Renal Replacement Therapy.

作者信息

Kim Steven, Heller James, Iqbal Zohora, Kant Rishi, Kim Eun Jung, Durack Jeremy, Saeed Maythem, Do Loi, Hetts Steven, Wilson Mark, Brakeman Paul, Fissell William H, Roy Shuvo

机构信息

From the *Department of Bioengineering and Therapeutic Sciences, †Division of Nephrology, University of California San Francisco, San Francisco, California; ‡Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California; §UCSF Imaging Center at China Basin, San Francisco, California; ¶Division of Pediatric Nephrology, University of California San Francisco, San Francisco, California; and ‖Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, Tennessee.

出版信息

ASAIO J. 2016 Mar-Apr;62(2):169-75. doi: 10.1097/MAT.0000000000000311.

Abstract

Silicon nanopore membranes (SNMs) with compact geometry and uniform pore size distribution have demonstrated a remarkable capacity for hemofiltration. These advantages could potentially be used for hemodialysis. Here, we present an initial evaluation of the SNM's mechanical robustness, diffusive clearance, and hemocompatibility in a parallel plate configuration. Mechanical robustness of the SNM was demonstrated by exposing membranes to high flows (200 ml/min) and pressures (1,448 mm Hg). Diffusive clearance was performed in an albumin solution and whole blood with blood and dialysate flow rates of 25 ml/min. Hemocompatibility was evaluated using scanning electron microscopy and immunohistochemistry after 4 hours in an extracorporeal porcine model. The pressure drop across the flow cell was 4.6 mm Hg at 200 ml/min. Mechanical testing showed that SNM could withstand up to 775.7 mm Hg without fracture. Urea clearance did not show an appreciable decline in blood versus albumin solution. Extracorporeal studies showed blood was successfully driven via the arterial-venous pressure differential without thrombus formation. Bare silicon showed increased cell adhesion with a 4.1-fold increase and 1.8-fold increase over polyethylene glycol (PEG)-coated surfaces for tissue plasminogen factor (t-PA) and platelet adhesion (CD41), respectively. These initial results warrant further design and development of a fully scaled SNM-based parallel plate dialyzer for renal replacement therapy.

摘要

具有紧凑结构和均匀孔径分布的硅纳米孔膜(SNMs)已显示出显著的血液滤过能力。这些优势有可能用于血液透析。在此,我们对平行板配置下的SNM的机械稳健性、扩散清除率和血液相容性进行了初步评估。通过将膜暴露于高流量(200毫升/分钟)和压力(1448毫米汞柱)来证明SNM的机械稳健性。在白蛋白溶液和全血中进行扩散清除率实验,血液和透析液流速均为25毫升/分钟。在体外猪模型中4小时后,使用扫描电子显微镜和免疫组织化学评估血液相容性。在200毫升/分钟时,流通池两端的压降为4.6毫米汞柱。机械测试表明,SNM可承受高达775.7毫米汞柱而不破裂。与白蛋白溶液相比,血液中的尿素清除率没有明显下降。体外研究表明,血液通过动静脉压差成功驱动,未形成血栓。裸硅表面的细胞黏附增加,组织纤溶酶原因子(t-PA)和血小板黏附(CD41)分别比聚乙二醇(PEG)涂层表面增加了4.1倍和1.8倍。这些初步结果为进一步设计和开发用于肾脏替代治疗的全尺寸基于SNM的平行板透析器提供了依据。

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