Lin Xiaojie, Ren Shen, Peng Ji, Wu Kan, Lood Christian, Galperin Anna, Graham Daniel J, Himmelfarb Jonathan, Ratner Buddy D
Department of Materials Science and Engineering, University of Washington, Seattle, WA 98195, USA.
Department of Mechanical Engineering, University of Washington, Seattle, WA 98195, USA.
Acta Biomater. 2025 Sep 1;203:332-345. doi: 10.1016/j.actbio.2025.07.021. Epub 2025 Jul 11.
Chronic Kidney Disease (CKD) affects a significant portion of the population, leading to end-stage renal disease (ESRD). ESRD is most often addressed by hemodialysis treatment, however, clinically significant interactions can occur between blood components, the dialysis membranes and the entire dialysis circuit. Zwitterionic compounds, such as polycarboxybetaine (PCB), are known for their ability to prevent blood protein adsorption and reduce platelet and complement activation. We synthesized and characterized two carboxybetaine (CB)-based copolymers tailored for coating the tubing and dialyzer components of the extracorporeal circuit. Utilizing both UV irradiation immobilization and a hydrophobic self-attachment technique, we successfully coated the tubing and dialyzer surfaces, respectively, with these zwitterionic copolymers. In vitro testing involved subjecting freshly drawn whole human blood through both, coated and uncoated circuits, under simulated hemodialysis circuit conditions. After one hour of continuous blood circulation and circuit contact, we assessed platelet and complement activation levels. Our results demonstrate significantly reduced platelet and complement activation and protein fouling on the zwitterionic-coated circuits compared to uncoated counterparts, indicating improved blood compatibility. This research underscores the potential of zwitterionic coatings as a promising approach to mitigate the need for continuous anticoagulation in hemodialysis treatment. By enhancing the blood compatibility of extracorporeal circuits, these coatings offer a safer and more effective solution for patients with ESRD undergoing hemodialysis. STATEMENT OF SIGNIFICANCE: Our research addresses a critical challenge in hemodialysis treatment, where the existing extracorporeal circuits often require continuous anticoagulation due to poor blood compatibility, leading to risks and complications for patients. By exploring the application of zwitterionic coatings, specifically polycarboxybetaine (PCB)-based materials, we offer a promising solution to enhance blood compatibility. Through the synthesis and characterization of two tailored carboxybetaine (CB)-based copolymers, we successfully coated tubing and dialyzer surfaces, significantly reducing platelet and complement activation in in vitro testing compared to uncoated circuits. These findings underscore the potential of zwitterionic coatings to improve the safety and effectiveness of hemodialysis treatment, paving the way for further research and potential clinical applications.
慢性肾脏病（CKD）影响着相当一部分人口，可导致终末期肾病（ESRD）。ESRD最常通过血液透析治疗来解决，然而，血液成分、透析膜和整个透析回路之间可能会发生具有临床意义的相互作用。两性离子化合物，如聚羧基甜菜碱（PCB），以其防止血液蛋白吸附以及减少血小板和补体激活的能力而闻名。我们合成并表征了两种基于羧基甜菜碱（CB）的共聚物，用于涂覆体外循环回路的管道和透析器部件。利用紫外线照射固定和疏水自附着技术，我们分别成功地用这些两性离子共聚物涂覆了管道和透析器表面。体外测试包括在模拟血液透析回路条件下，让新鲜采集的全血通过涂覆和未涂覆的回路。在持续血液循环和回路接触一小时后，我们评估了血小板和补体的激活水平。我们的结果表明，与未涂覆的回路相比，两性离子涂覆的回路上血小板和补体激活以及蛋白质污垢显著减少，表明血液相容性得到改善。这项研究强调了两性离子涂层作为一种有前景的方法来减少血液透析治疗中持续抗凝需求的潜力。通过提高体外循环回路的血液相容性，这些涂层为接受血液透析的ESRD患者提供了一种更安全、更有效的解决方案。重要性声明：我们的研究解决了血液透析治疗中的一个关键挑战，即现有的体外循环回路由于血液相容性差，通常需要持续抗凝，给患者带来风险和并发症。通过探索两性离子涂层的应用，特别是基于聚羧基甜菜碱（PCB）的材料，我们提供了一种增强血液相容性的有前景的解决方案。通过合成和表征两种定制的基于羧基甜菜碱（CB）的共聚物，我们成功地涂覆了管道和透析器表面，与未涂覆的回路相比，在体外测试中显著降低了血小板和补体激活。这些发现强调了两性离子涂层改善血液透析治疗安全性和有效性的潜力，为进一步研究和潜在的临床应用铺平了道路。
