A dual-functional anti-thrombotic hydrogel coating integrating immunomodulation and surface passivation for vascular...

Cardiovascular implantable devices, such as central venous catheters, often induce thrombus formation in clinical applications. Conventional antithrombotic coatings show limited efficacy in high-risk patients with systemic inflammatory conditions due to their inability to modulate the interplay between inflammation and coagulation. To address this limitation, this study developed a synergistic anti-thrombotic hydrogel coating that combines surface passivation and immunomodulatory functions. A stable zwitterionic coating was fabricated on polyurethane (PU) substrates via redox-initiated surface-initiated polymerization, with grafting of 2-methacryloyloxyethyl phosphorylcholine (MPC) and the free radical scavenger 4-amino-2,2,6,6-tetramethylpiperidin-1-oxyl (Tempol). In vitro experiments demonstrated that the coating not only significantly reduced protein adsorption and platelet adhesion, exhibiting good antithrombotic properties, but also showed outstanding free radical scavenging capability and good cytocompatibility. Furthermore, it induced the shift of macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. To further evaluate its in vivo performance, a lipopolysaccharide (LPS)-induced systemic inflammation rabbit model was established. In vivo results indicated that, compared to both unmodified PU and the MPC/acrylic acid hydrogel-coated PU (PU-MA), the Tempol-modified coating (PU-MA-Tp) significantly reduced thrombus formation on the catheter surface under inflammatory conditions. It also effectively mitigated inflammatory cell infiltration in the surrounding tissues. Additionally, the PU-MA-Tp coating promoted macrophage polarization toward the anti-inflammatory M2 phenotype. This study suggests that a strategy aimed at synergistically regulating the material-bio interface and the local immune microenvironment may help sustain the antithrombotic properties of the material in inflammatory conditions, offering a potential direction for the design of antithrombotic blood-contacting devices for high-risk patients. STATEMENT OF SIGNIFICANCE: Cardiovascular devices are widely used in clinical practice but remain highly prone to thrombosis and infection in patients with systemic inflammation or immune dysfunction. Conventional antithrombotic coatings mainly reduce protein adsorption or release anticoagulants, yet neglect the inflammatory microenvironment tightly coupled with coagulation, leading to limited efficacy under oxidative stress. This study presents a dual-function coating that integrates 2-methacryloyloxyethyl phosphorylcholine (MPC) with the reactive oxygen species (ROS) scavenger 4-amino-2,2,6,6-tetramethylpiperidin-1-oxyl (Tempol) to achieve synergistic antithrombotic and immunomodulatory effects. The coating suppresses protein adhesion, reduces oxidative stress, and attenuates pro-inflammatory signaling, thereby disrupting the inflammation-coagulation feedback loop. Validation in a lipopolysaccharide (LPS)-induced inflammation and catheter implantation "two-hit" model highlights its translational potential. This work advances biomaterial design toward integrated immune and redox regulation for high-risk patients.