Endothelial membrane mimetic coating modified dialyzer for hemocompatible and anticoagulant-free hemodialysis

Abstract

Current hemodialysis requires a dilemmatic balance between under- and over-heparinization to prevent extracorporeal circuit clotting and bleeding complications. Here we report an endothelial membrane mimetic coating (EMMC) strategy to replace the systemic heparinization by enhancing the hemocompatibility and anticoagulation property of all the blood contacting surfaces. The EMMC is created by precoating of polydopamine, multi-point anchoring of a sulfobetaine and carboxyl side-chain copolymer (PSBC) and grafting of unfractionated heparin (UFH). The multi-point anchored PSBC layer forms an ultra-thin cell outer membrane zwitterion mimicking interface to enhance hemocompatibility, while the grafted UFH molecules mimic anticoagulant molecules attached on endothelial membrane to endow superior anticoagulation activity. Compared to a commercial polysulfone (PSf) dialysis membrane, the EMMC coated membrane can reduce protein adsorption, platelet adhesion and complement activation by 94.1 %, 98.9 % and 77 %, respectively. Meanwhile, anticoagulation properties, including clotting time, surface thrombus formation time and thrombin inactivation efficacy, are significantly improved compared to currently reported heparin coatings. More importantly, anticoagulant-free extracorporeal circulation using the EMMC modified PSf dialyzer circuit in a beagle dog model was performed smoothly for 2 h without any observable thrombus. Furthermore, main dialysis parameters of the modified hemodialyzer were not decreased. In conclusion, this highly hemocompatible and strong anticlotting endothelial membrane mimetic coating has great potential to replace the systemic heparinization in hemodialysis.