Department of Materials Engineering , Ming Chi University of Technology , Taishan, New Taipei City 24301 , Taiwan.
Department of Chemical and Materials Engineering , Chang Gung University , Guishan , Taoyuan 33302 , Taiwan.
ACS Appl Mater Interfaces. 2019 Nov 27;11(47):43843-43856. doi: 10.1021/acsami.9b14351. Epub 2019 Nov 12.
Protein-bound uremic toxins (PBUTs) can cause noxious effects in patients suffering from renal failure as a result of inhibiting the transport of proteins and inducing their structural modification. They are difficult to remove through standard hemodialysis (HD) treatment. Herein, we report an organic bioelectronic HD device system for the effective removal of PBUTs through electrically triggered dissociation of protein-toxin complexes. To prepare this system, we employed electrospinning to fabricate electrically conductive quaternary composite nanofiber mats-comprising multiwalled carbon nanotubes (MWCNTs), poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS), poly(ethylene oxide) (PEO), and (3-glycidyloxypropyl)trimethoxysilane (GOPS)-on conventional polyethersulfone (PES) dialysis membranes. These composite nanofiber platforms exhibited (i) long-term water resistance (due to cross-linking among PSS, PEO, and GOPS), (ii) high adhesion strength on the PES membrane (due to GOPS functioning as an adhesion promoter), (iii) enhanced electrical properties [due to the MWCNTs and PEDOT:PSS promoting effective electrical stimulation (ES) operation in devices containing bioelectronic interfaces (BEI)], and (iv) good anticoagulant ability and negligible hemolysis of red blood cells. We employed this organic BEI electronic system as a novel single-membrane HD device to study the removal efficiency of four kinds of uremic toxins [-cresol (PC), indoxyl sulfate, and hippuric acid as PBUTs; creatinine as a non-PBUT] as well as the effects of ES on lowering the protein binding ratio. Our organic BEI devices provided a high rate of removal of PC with low protein loss after 4 h of a simulated dialysis process. It also functioned with low complement activation, low contact activation levels, and lower amounts of platelet adsorption, suggesting great suitability for use in developing next-generation bioelectronic medicines for HD.
蛋白结合性尿毒症毒素(PBUTs)可通过抑制蛋白转运并诱导其结构修饰,对肾衰竭患者产生有害影响。它们很难通过标准血液透析(HD)治疗去除。在此,我们报告了一种有机生物电子 HD 设备系统,可通过电触发蛋白-毒素复合物的解离来有效去除 PBUTs。为了制备该系统,我们采用静电纺丝技术制备了导电的季铵复合纳米纤维垫,包含多壁碳纳米管(MWCNTs)、聚(3,4-亚乙基二氧噻吩):聚苯乙烯磺酸盐(PEDOT:PSS)、聚(氧化乙烯)(PEO)和(3-缩水甘油丙基)三甲氧基硅烷(GOPS),并将其置于传统的聚醚砜(PES)透析膜上。这些复合纳米纤维平台表现出(i)长期耐水性(由于 PSS、PEO 和 GOPS 之间的交联),(ii)在 PES 膜上的高粘附强度(由于 GOPS 作为粘附促进剂发挥作用),(iii)增强的电性能[由于 MWCNTs 和 PEDOT:PSS 促进包含生物电子接口(BEI)的设备中的有效电刺激(ES)操作],以及(iv)良好的抗凝血能力和对红细胞的溶血作用可忽略不计。我们将这种有机 BEI 电子系统用作新型单膜 HD 设备,以研究四种尿毒症毒素[间-甲酚(PC)、吲哚硫酸酯和马尿酸作为 PBUTs;肌酸酐作为非 PBUT]的去除效率以及 ES 对降低蛋白结合比的影响。我们的有机 BEI 设备在模拟透析过程 4 小时后提供了高去除率的 PC 和低蛋白损失。它还具有低补体激活、低接触激活水平和低血小板吸附量,表明非常适合用于开发下一代用于 HD 的生物电子药物。