Geremia I, Pavlenko D, Maksymow K, Rüth M, Lemke H D, Stamatialis D
(Bio)artificial organs, Department of Biomaterials Science and Technology, TechMed Centre, Faculty of Science and Technology, University of Twente, P.O. Box 217, 7500 AE Enschede, the Netherlands.
eXcorLab GmbH, Industrie Center Obernburg, Obernburg, Germany.
Acta Biomater. 2020 Jul 15;111:118-128. doi: 10.1016/j.actbio.2020.05.016. Epub 2020 May 21.
The patients with end stage kidney disease need haemodialysis therapies, using an artificial kidney. Nevertheless, the current therapies cannot remove a broad range of uremic toxins compared to the natural kidney. Adsorption therapies, using sorbent-based columns, can improve the clearance of uremic toxins, but the sorbent particles often require polymeric coatings to improve their haemocompatibility leading to mass transfer limitations and to lowering of their performance. Earlier, we have developed a dual layer Mixed Matrix fiber Membrane (MMM) based on polyethersulfone/polyvinylpyrrolidone (PES/PVP) polymer blends. There, the sorbent activated carbon particles are embedded in the outer membrane layer for achieving higher removal whereas the inner blood contacting selective membrane layer should achieve optimal blood compatibility. In this work, we evaluate in detail the haemocompatibility of the MMM following the norm ISO 10993-4. We study two generations of MMM having different dimensions and transport characteristics; one with low flux and no albumin leakage and another with high flux but some albumin leakage. The results are compared to those of home-made PES/PVP single layer hollow fiber and to various control fibers already applied in the clinic. Our results show that the low flux MMM successfully avoids contact of blood with the activated carbon and has good haemocompatibility, comparable to membranes currently used in the clinic. STATEMENT OF SIGNIFICANCE: Haemodialysis is a life-sustaining extracorporeal treatment for renal disease, however a broad range of uremic toxins cannot still be removed. In our previous works we showed that a double layer Mixed Matrix Membrane (MMM) composed of polyethersulfone/polyvinylpyrrolidone and activated carbon can achieve higher removal of uremic toxics compared to commercial haemodialysers. In this work we evaluate the haemocompatibility profile of the MMM in order to facilitate its clinical implementation. The lumen particle-free layer of the MMM successfully avoids the contact of blood with the poorly blood-compatible activated carbon. Moreover, thanks to the high amount of polyvinylpyrrolidone and to the smoothness of the lumen layer, the MMM has very good haemocompatibility, comparable to membranes currently used in the clinic.
终末期肾病患者需要使用人工肾进行血液透析治疗。然而，与天然肾脏相比，目前的治疗方法无法清除多种尿毒症毒素。使用基于吸附剂的柱的吸附疗法可以提高尿毒症毒素的清除率，但吸附剂颗粒通常需要聚合物涂层来改善其血液相容性，这会导致传质限制并降低其性能。早些时候，我们开发了一种基于聚醚砜/聚乙烯吡咯烷酮（PES/PVP）聚合物共混物的双层混合基质纤维膜（MMM）。在那里，吸附剂活性炭颗粒嵌入外膜层以实现更高的去除率，而内部与血液接触的选择性膜层应实现最佳的血液相容性。在这项工作中，我们按照ISO 10993-4标准详细评估了MMM的血液相容性。我们研究了两代具有不同尺寸和传输特性的MMM；一代通量低且无白蛋白渗漏，另一代通量高但有一些白蛋白渗漏。将结果与自制的PES/PVP单层中空纤维以及临床中已应用的各种对照纤维的结果进行比较。我们的结果表明，低通量MMM成功避免了血液与活性炭接触，具有良好的血液相容性，与目前临床使用的膜相当。
血液透析是一种维持肾病患者生命的体外治疗方法，然而仍有多种尿毒症毒素无法清除。在我们之前的工作中，我们表明由聚醚砜/聚乙烯吡咯烷酮和活性炭组成的双层混合基质膜（MMM）与商业血液透析器相比，可以实现更高的尿毒症毒素去除率。在这项工作中，我们评估了MMM的血液相容性，以便于其临床应用。MMM的内腔无颗粒层成功避免了血液与血液相容性差的活性炭接触。此外，由于大量的聚乙烯吡咯烷酮和内腔层的光滑度，MMM具有非常好的血液相容性，与目前临床使用的膜相当。
