Engineering cross-linked polyvinyl alcohol/ polyethersulfone hemodialysis membrane for simultaneously inhibiting platelet adhesion and activation and alleviating severe oxidative stress

End-stage kidney dialysis therapy is often accompanied by severe oxidative stress, which significantly increases patient mortality. To address this issue, anti-oxidative hemodialysis membranes have emerged. Meanwhile, the surface of hemodialysis membranes also faces poor blood compatibility and thrombocytopenia problems, closely related to platelet activation and adhesion. In this work, we develop a series of polyethersulfone@ polyvinyl alcohol- l -Arginine (PES@PVA-L-Arg) gel membranes. Specifically, polyvinyl alcohol (PVA) macromolecules are crosslinked with N 1 -(4-boronobenzyl)- N 3 -(4-boronophenyl)- N 1 , N 1 , N 3 , N 3 -tetramethylpropane-1,3-diam-inium (TSPBA), while l -Arginine (L-Arg) molecules are simultaneously embedded into the PES/PVA membrane as a nitric oxide (NO) donor. The results reveal that the PES@PVA1-L-Arg inhibits the platelets' adhesion and activation onto the surface of the membrane, with the number of activated platelets reduced by 38 % compared to the PES membrane. This inhibition is achieved through the hydrated PVA layer and the release of NO in a reactive oxygen species (ROS) microenvironment. Additionally, the PES@PVA1-L-Arg membrane demonstrates superior ROS scavenging capacity, neutralizing 40.62 % of ABTS• + via TSPBA and 73.66 % of H 2 O 2 through the combined effects of TSPBA and L-Arg. Basically, the hemodialysis function meets the requirement under the simulated scenario, with the bovine serum albumin rejection of 96.09 %, lysozyme, and urea sieving coefficients of 77.85 % and 92.03 %, respectively. Moreover, the safety of the membranes is confirmed by hemocompatibility tests, including clotting tests, blood cell counting statistics tests, C3a and C5a levels, and hemolysis ratio. Overall, our work presents a promising PES@PVA1-L-Arg membrane that not only inhibits platelet activation and adhesion but also alleviates severe oxidative stress for clinical hemodialysis.