First Implantation of Silicon Nanopore Membrane Hemofilters.
First Implantation of Silicon Nanopore Membrane Hemofilters.
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DOI：
10.1097/mat.0000000000000367
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发表时间：
2016-07
期刊：
影响因子：
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通讯作者：
Fissell WH
中科院分区：
文献类型：
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作者：
Kensinger C;Karp S;Kant R;Chui BW;Goldman K;Yeager T;Gould ER;Buck A;Laneve DC;Groszek JJ;Roy S;Fissell WH
用于治疗肾衰竭的可拆卸血液滤过器主要取决于膜的传输特性以及膜、滤芯和血液导管的生物相容性。一种具有狭缝状孔的新型膜优化了渗透性和选择性之间的权衡，使植入治疗成为可能。通过考虑化学相互作用的亚纳米尺度和血液流体动力学的毫米尺度的生物相容性，实现了植入的平行板血液滤过器的持续（3-8）天功能，具有最低限度的抗凝作用。用聚乙二醇对具有5-8 nm 2微米狭缝形孔的总共400 nm厚的多晶硅平板膜进行表面改性。基于血流的计算流体动力学预测，对血液滤过器滤芯的几何形状进行了优化。在一项非对照初步研究中，将硅滤器植入6只A级犬中。通过与主动脉和下腔静脉的吻合将滤芯连接到心血管系统，并将滤液引流到位于腹膜中的收集袋中。每天两次给予止痛药和乙酰水杨酸，直至在术后第3天（n = 2）、第4天（n = 2）、第5天（n = 1）和第8天（n = 1）收集血液滤过器。无血液滤过器血栓形成。处理5天和8天的动物在硅纳米孔膜中有显微镜下的断裂，并且在取出时收集袋中有20-50 ml渗出液（白蛋白筛分系数0.5 - 0.7）。较短的实验持续时间（3-4天）导致的滤过容量与基于平均动脉压和膜透水性的预测相似，并且与植入前测量结果相似（Δ 0.2 - 0.3）。总之，对血液-材料相互作用的详细机制和材料科学关注允许植入的血液滤过器抵抗血栓形成。需要额外的测试来确定最佳的膜特性，并确定长期植入的限制因素。
An implantablehemofilter for the treatment of kidney failure depends critically on the transport characteristics of the membrane and the biocompatibility of the membrane, cartridge, and blood conduits. A novel membrane with slit-shaped pores optimizes the trade-off between permeability and selectivity, enabling implanted therapy. Sustained (3–8) day function of an implanted parallel-plate hemofilter with minimal anticoagulation was achieved by considering biocompatibility at the subnanometer scale of chemical interactions and the millimeter scale of blood fluid dynamics. A total of 400 nm-thick polysilicon flat sheet membranes with 5–8 nm 2 micron slit-shaped pores were surface-modified with polyethylene glycol. Hemofilter cartridge geometries were refined based on computational fluid dynamics predictions of blood flow. In an uncontrolled pilot study, silicon filters were implanted in six class A dogs. Cartridges were connected to the cardiovascular system by anastamoses to the aorta and inferior vena cava and filtrate was drained to collection pouches positioned in the peritoneum. Pain medicine and acetylsalicylic acid were administered twice daily until the hemofilters were harvested on postoperative days 3 (n = 2), 4 (n = 2), 5 (n = 1), and 8 (n = 1). No hemofilters were thrombosed. Animals treated for 5 and 8 days had microscopic fractures in the silicon nanopore membranes and 20–50 ml of transudative (albumin sieving coefficient 0.5 – 0.7) fluid in the collection pouches at the time of explant. Shorter experimental durations (3–4 days) resulted in filtration volumes similar to predictions based on mean arterial pressures and membrane hydraulic permeability and (∼ 0.2 – 0.3), similar to preimplantation measurements. In conclusion, a detailed mechanistic and materials science attention to blood–material interactions allows implanted hemofilters to resist thrombosis. Additional testing is needed to determine optimal membrane characteristics and identify limiting factors in long-term implantation.