Dual Layer Mixed Matrix Hollow Fiber Membranes for Outside-In Filtration of Human Blood Plasma

O. T. Beek, M. Gelder, C. Lokhorst, Diënty H. M. Hazenbrink, B. H. Lentferink, K. Gerritsen, D. Stamatialis
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Abstract

Hemodialysis mainly removes small water-soluble uremic toxins but cannot effectively remove middle molecules and protein-bound uremic toxins. Besides, the therapy is intermittent leading to fluctuating blood values and fluid status which adversely impacts patients’ health. Prolonged hemodialysis could improve the removal of toxins and the development of portable and wearable artificial kidneys could offer more flexibility in the dialysis scheme. This would enhance patients’ overall health, autonomy, mobility and flexibility, allowing patients to participate in social and economic life. However, during prolonged hemodialysis, blood clots could obstruct the fiber lumen, resulting in a decrease of the effective membrane surface area available for toxin removal. The outside-in filtration (OIF) mode, wherein blood flows through the inter-fiber space instead of through the fiber lumina, has been applied widely in blood oxygenators to prevent fiber clotting, but not in hemodialysis. In this study, we present for the first time the development of a mixed matrix membrane (MMM) for OIF of human blood plasma. This MMM combines diffusion and adsorption and consists of a polymeric membrane matrix with activated carbon (AC) particles on the inside layer, and a polymeric particle-free layer on the outer fiber layer. Our results show that in vitro MMM fibers for OIF demonstrate superior removal of the protein-bound uremic toxins, indoxyl sulfate and hippuric acid, compared to both earlier MMM fibers designed for inside-out filtration mode and commercial high-flux fibers.
双层混合基质中空纤维膜用于人血浆的内外过滤
血液透析主要去除水溶性尿毒症毒素,但不能有效去除中间分子和蛋白质结合的尿毒症毒素。此外,治疗是间歇性的,导致血液值和液体状态波动,对患者的健康产生不利影响。长时间的血液透析可以改善毒素的清除,便携式和可穿戴人工肾脏的开发可以在透析方案中提供更大的灵活性。这将增强患者的整体健康、自主性、机动性和灵活性,使患者能够参与社会和经济生活。然而,在长时间的血液透析过程中,血凝块会阻塞纤维管腔,导致可用于毒素去除的有效膜表面积减少。外向内过滤(OIF)模式,即血液通过纤维间空间而不是通过纤维腔流动,已广泛应用于血液氧合器中以防止纤维凝血,但在血液透析中尚未得到应用。在这项研究中,我们首次提出了用于人血浆OIF的混合基质膜(MMM)的开发。这种MMM结合了扩散和吸附,由内层带有活性炭(AC)颗粒的聚合膜基质和外层纤维层的无聚合物颗粒层组成。我们的研究结果表明,与早期设计用于内向外过滤模式的MMM纤维和商用高通量纤维相比,体外用于OIF的MMM纤维具有更好的去除蛋白质结合的尿毒症毒素、硫酸吲哚酚和马尿酸的能力。
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