“Continuously Touching ROS into NO” by Hemodialysis Membranes for Preventing Hemodialysis-Associated Thrombocytopenia

Hemodialysis membranes would easily accelerate excessive oxidative stress, leading to platelet adhesion and aggregation, which cause exacerbation of hemodialysis-associated thrombocytopenia. Notably, nitric oxide (NO) gas exerts an inhibitory effect on platelet activation by targeting key signaling molecules. Hence, we propose a strategy to inhibit platelet activation and adhesion by turning "harmful reactive oxygen species (ROS)" into "beneficial NO", thereby preventing hemodialysis-associated thrombocytopenia. In this study, polydopamine-l-arginine (PDA-LA) molecules are coated onto the membrane surface to mainly enhance the mitigation of oxidative stress, while oxidized hyaluronic acid-l-arginine (OHA-LA) molecules are stably cross-linked into the membrane to ensure the sustained NO release for inhibition of platelet adhesion. As a result, the reactive oxygen and nitrogen species (RONS) scavenging capacities are improved to follow: H₂O₂ (50%), 2,2-diphenyl-1-picrylhydrazyl (DPPH^•, 85.60%), 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) radical (ABTS^•+, 82.81%), and O₂^•- (0.125 U/mg). Surprisingly, the concentration of continuously released NO is still approximately 0.590 μM after six cycles (0.557 μM in the first cycle). Importantly, the platelet adhesion experiment demonstrates a sustained inhibition of platelet adhesion, diminished by a factor of 100 per square centimeter (100/cm²). In a simulated sieving experiment, the BSA rejection ratio (97.52%) and urea sieving ratio (98.38%) both meet the basic requirements for hemodialysis membranes. Thus, the obtained PES/PVA/OA@PA membrane is a promising candidate for preventing hemodialysis-associated thrombocytopenia.