Hydrophobic-modified heparin coatings with adaptively anti-thrombotic and anti-bacterial functions for interventional cardiovascular catheters

Interventional cardiovascular catheters (ICCs) are prone to complications such as venous thrombosis and occlusion during clinical applications, primarily due to the gradual adhesion and accumulation of cells, proteins, and microorganisms on their surfaces. Heparin sodium (HS) represents a typical clinically antithrombotic agent, whereas its hydrophilicity usually limits stable binding to hydrophobic catheter surfaces. Herein, we propose an easy-operating one-step strategy for fabricating hydrophobic-modified heparin based on electrostatic assembly between ethyl lauroyl arginate (ELA), a cationic antimicrobial compound, and anionic HS. The resulting ELA-HS complex shows water-insoluble and alcohol-soluble features, which can form a uniform and robust coating driven by electrostatic and hydrophobic interactions upon a series of catheters with diverse shapes and multi-cavity structures via solvent immersion. Molecular dynamics (MD) simulation elucidated the formation mechanism of hydrophobic-modified heparin, as well as the assembly mechanism between the coating and substrates. Importantly, this obtained ELA-HS coating with adaptive dissociation effectively resists the adsorption of fibrinogen and significantly reduces the adhesion of blood cells, including platelets, lymphocytes, and monocytes. Leveraging ELA’s inherent bactericidal properties, the coating also demonstrates substantial antibacterial efficacy, reducing bacterial colonization by over 99% whether gram-negative Escherichia coli ( E.coli. ) and gram-positive Staphylococcus aureus ( Sa. ). In vivo validation further confirms the coating’s dual functionality in preventing thrombosis and microbial infection, even in stringent acute models of canine jugular vein implantation. This ELA-HS modification strategy offers a practical solution to enhance the hemocompatibility and infection resistance of interventional catheters, addressing critical clinical challenges associated with thrombosis and bacterial adhesion.