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Construction of electro-neutral surface on dialysis membrane for improved toxin clearance and anti-coagulation/inflammation through saltwater fish inspired trimethylamine N-oxide (TMAO)
Journal of Membrane Science ( IF 9.5 ) Pub Date : 2021-09-21 , DOI: 10.1016/j.memsci.2021.119900
Yang Liu 1, 2 , Guiliang Li 1, 2 , Qiu Han 1 , Haibo Lin 1 , Qiang Li 3 , Gang Deng 4 , Fu Liu 1, 2
Affiliation  

Dialysis membranes capable of preventing coagulation and inflammation and achieving high toxin clearances are highly desired for clinical hemodialysis. Here, we constructed an electro-neutral and hydrophilic surface on Polysulfone (PSf) membrane, which both improved the hemocompatibility and toxin clearance. The membrane surface was modified with trimethylamine N-oxide (TMAO) through Michael addition reaction and subsequent crosslinking with glycidyl ether oxypropyl trimethoxysilane (KH560). Saltwater fish inspired zwitterionic monomer TMAO without spacers between positive and negative headgroups is thought to generate a hydrated and net-charged layer that prevents non-specific plasma proteins and platelets adsorption and activation. Coagulation time, serine protease Factor XIIa, bradykinin (BK), kallikrein (KLK) and anaphylatoxins (C3, C5 and SC5b-9) were examined to explore blood compatibility. All results showed that the highly hydrated and electro-neutral surface could efficiently alleviate the activation of the coagulation cascade, kallikrein-kinin system (KKS) and complement system simultaneously. Furthermore, the modified PSf membrane is favorable to toxins clearance (e.g., urea, creatine, lysozyme and vitamin B12) during simulated dialysis process. It is manifested that the TMAO based surface modification is feasible for improving the hemocompatibility and toxin clearance of dialysis membranes.



中文翻译:

在透析膜上构建电中性表面以通过海水鱼激发的三甲胺 N-氧化物 (TMAO) 改善毒素清除和抗凝/炎症

临床血液透析非常需要能够防止凝血和炎症并实现高毒素清除的透析膜。在这里,我们在聚砜 (PSf) 膜上构建了一个电中性和亲水性表面,既提高了血液相容性,又提高了毒素清除率。通过迈克尔加成反应和随后与缩水甘油醚氧基丙基三甲氧基硅烷(KH560)交联,用三甲胺N-氧化物(TMAO)改性膜表面。海水鱼启发了两性离子单体 TMAO,在正负头基之间没有间隔物,被认为会产生水合和净电荷层,防止非特异性血浆蛋白和血小板吸附和活化。凝血时间、丝氨酸蛋白酶因子 XIIa、缓激肽 (BK)、激肽释放酶 (KLK) 和过敏毒素 (C3、检查 C5 和 SC5b-9) 以探索血液相容性。所有结果表明,高度水合和电中性的表面可以同时有效地减轻凝血级联、激肽释放酶-激肽系统 (KKS) 和补体系统的激活。此外,改性PSf膜有利于模拟透析过程中的毒素清除(如尿素、肌酸、溶菌酶和维生素B12)。表明基于TMAO的表面改性对于提高透析膜的血液相容性和毒素清除是可行的。改性PSf膜有利于模拟透析过程中的毒素清除(如尿素、肌酸、溶菌酶和维生素B12)。表明基于TMAO的表面改性对于提高透析膜的血液相容性和毒素清除是可行的。改性PSf膜有利于模拟透析过程中的毒素清除(如尿素、肌酸、溶菌酶和维生素B12)。表明基于TMAO的表面改性对于提高透析膜的血液相容性和毒素清除是可行的。

更新日期:2021-09-24
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