Mimicking Macrophage Immune Mechanism for Infection and Thrombosis Prevention on a Dual‐Activity Hybrid Enzyme‐Assembled Surface

Surfaces with antithrombotic and anti‐infective properties are essential for ensuring the successful clinical performance of extracorporeal circuits and indwelling medical devices. However, current surface technologies designed to achieve such dual biological functions are often limited by complex procedures and insufficient duration of efficacy. Herein, mimicking the innate immune mechanism of macrophages, wherein they eliminate pathogens through the synergistic action of nitric oxide (NO) and lysozyme secreted by them, we report a bioinspired glutathione peroxidase mimic (i.e., 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid‐Cu (II)(DOTA‐Cu) coordination complex)‐engineered lysozyme (DOTA‐Cu/Lyz) self‐assembling coating for tailoring anti‐thrombotic and anti‐infective functions. This self‐assembled DOTA‐Cu/Lyz coating exhibits potent GPx‐mimicking activity, catalyzing the decomposition of endogenous S‐nitrosothiol into NO under blood conditions. This process synergizes with lysozyme to effectively kill bacteria, thereby mimicking the pathogen‐killing mechanism of macrophages. Meanwhile, the sustained release of NO inhibits platelet activation and adhesion via NO‐cyclic guanosine monophosphate (cGMP) signaling pathway, providing long‐lasting antithrombotic effects. Overall, such self‐assembled DOTA‐Cu/Lyz coating represents a promising strategy to address the issue of thrombosis and infection associated with blood‐contacting devices.