A Zwitterionic Catalytic Coating for In Situ Nitric Oxide Generation Enables Synergistic Antithrombotic and Anti-Inflammatory Effects for Blood-Contacting Devices

The use of extracorporeal life support and indwelling blood-contacting devices in critically ill patients is frequently complicated by device-associated thrombosis, a persistent clinical challenge not fully addressed by current antithrombogenic coatings. This limitation is largely attributable to the profound systemic inflammatory state inherent to critical illness, which drives a hypercoagulable milieu through mechanisms of immunothrombosis that conventional coatings fail to mitigate. To address this dual pathophysiological challenge, we designed a novel composite coating comprising a zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) coordinated with copper ions (Cu(II)). This dual-functional strategy integrates the passive antifouling properties of the PMPC layer with the active, localized generation of nitric oxide (NO) catalyzed by Cu(II) from endogenous S-nitrosothiols. Systematic evaluation under both static and dynamic conditions, including blood models simulating critical illness inflammation, demonstrated that the PCDA coating synergistically resists protein adsorption and inhibits platelet activation; the coating provides superior protection against thrombus formation and inflammatory activation compared to conventional monofunctional surfaces. These findings suggest a translational advance toward enhancing the hemocompatibility and safety of life-support devices in the high-acuity ICU setting.