Gallic acid carbon dot-supported heparin-like polymer as an optimized membrane-anchored anticoagulant for functionalization of hemodialysis membranes

GA-CDs impart durable antioxidant and anticoagulant activity to polyethersulfone (PES) membranes. • GA-CDs promote macrophage Nrf2 nuclear translocation and reduce ROS and endothelial TF expression. • The membrane showed 83% DPPH and 97% ABTS⁺ scavenging, APTT of ~420 s, and reduced platelet adhesion and PF4 release. Conventional hemodialysis membranes exhibit suboptimal blood compatibility, predisposing patients to thrombotic events and oxidative stress-associated complications that accelerate disease progression. To address this challenge, we developed a gallic acid carbon dots (GA-CDs)-functionalized polyethersulfone (PES) membrane via polydopamine-assisted co-deposition of nitrogen-doped GA-CDs and a heparin-mimetic polymer. The resulting membrane features stable surface immobilization of GA-CDs, conferring durable hemocompatibility and intrinsic dual functionality: (i) sustained ROS-scavenging-driven antioxidant activity for long-term oxidative stress mitigation; and (ii) enhancement of anticoagulant performance through suppression of oxidative stress-mediated tissue factor (TF) activation, thereby synergistically preventing thrombosis. Mechanistically, GA-CDs activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling cascade to upregulate endogenous antioxidant enzymes, efficient reactive oxygen species (ROS) clearance, and protection against oxidative cellular damage. Concurrently, by scavenging ROS, GA-CDs suppressed oxidative stress–induced tissue factor activation, establishing a functional link between redox homeostasis and coagulation regulation. In vitro evaluation demonstrated outstanding dual functionality: potent free radical scavenging capacity (83% DPPH and 97% ABTS⁺ scavenging), significantly prolonged activated partial thromboplastin time (APTT 420 s, 8.4-fold increase vs. control), excellent cytocompatibility, and markedly improved hemocompatibility. Collectively, these findings highlight the translational promise of this rationally designed dual-action hemodialysis membrane, where localized durable ROS scavenging and surface-confined anticoagulation operate in concert to mitigate key pathophysiological drivers of dialysis-associated complications. Download: Download high-res image (270KB) Download: Download full-size image Polydopamine (PDA)-assisted co-deposition of poly(sodium 4-styrenesulfonate) (PSSNa) and gallic acid carbon dots (GA-CDs) enabled multifunctional surface modification of polyethersulfone (PES) hemodialysis membranes. Furthermore, cellular experiments demonstrated that GA-CDs promoted the nuclear accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2), reduced intracellular reactive oxygen species (ROS) levels, and suppressed oxidative stress-induced upregulation of endothelial tissue factor (TF). The modified membrane exhibited excellent antioxidant activity, achieving DPPH and ABTS⁺ radical scavenging rates of 83% and 97%, respectively. It also prolonged coagulation times, reduced platelet adhesion and platelet factor 4 (PF4) release, and improved hemocompatibility.