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.

中文翻译：

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用于血液相容性和无抗凝剂血液透析的内皮膜模拟涂层改良透析器

目前的血液透析需要在肝素化不足和过度之间取得两难的平衡，以防止体外回路凝血和出血并发症。在这里，我们报告了一种内皮膜模拟涂层（EMMC）策略，通过增强所有血液接触表面的血液相容性和抗凝特性来取代全身肝素化。 EMMC 是通过聚多巴胺预涂层、磺基甜菜碱和羧基侧链共聚物 (PSBC) 的多点锚定以及普通肝素 (UFH) 的接枝而形成的。多点锚定的PSBC层形成超薄细胞外膜两性离子模拟界面以增强血液相容性，而接枝的UFH分子模拟附着在内皮膜上的抗凝分子以赋予优异的抗凝活性。与商用聚砜（PSf）透析膜相比，EMMC涂层膜可分别减少94.1%、98.9%和77%的蛋白质吸附、血小板粘附和补体激活。同时，与目前报道的肝素涂层相比，其抗凝性能，包括凝血时间、表面血栓形成时间和凝血酶灭活功效均得到显着改善。更重要的是，使用 EMMC 改进的 PSf 透析器电路在比格犬模型中进行的无抗凝体外循环顺利进行了 2 小时，没有观察到任何血栓。此外，改良后的血液透析器的主要透析参数并未降低。总之，这种高度血液相容性和强抗凝血的内皮膜模拟涂层具有替代血液透析中全身肝素化的巨大潜力。