A Facile, Scalable, and Universal Strategy to Construct Densely Packed <scp>l</scp> -Lysine-Derived Zwitterionic Brushes for Blood-Contacting Catheters

Thrombus formation associated with blood-contacting catheters remains a prevalent clinical issue. Antithrombotic coatings capable of inhibiting coagulation activation without interfering with hemostasis are highly desired. Herein, we constructed thick and densely packed poly(ε-acryloyl l-lysine) (p(LysAA)) zwitterionic brushes on the inner wall of chemical inert polyethylene (PE) catheters <i>via</i> a recently developed universal, substrate-independent coating strategy that enables facile scaling-up for catheters with complex geometries. The densely packed l-lysine-derived zwitterionic brushes exhibited ultrahydrophilic properties, with water contact angles below 10°. As expected, fouling by bovine serum albumin, fibrinogen, bacteria, platelets, and red blood cells was effectively suppressed. Moreover, the brushes demonstrated excellent biocompatibility, as evidenced by relative cell growth rates of over 90%, a hemolysis rate of below 1%, and intradermal reaction scores of less than 1.0. Importantly, it showed antithrombotic efficacy both <i>in vitro</i> and an <i>in vivo</i>. In a rabbit arterio-jugular vein shunt model, no obvious clotting was observed after 1 h of circulation. Overall, the brushes hold significant clinical potential in reducing the level of thrombus formation for blood-contacting catheters. Furthermore, by leveraging the abundant reactive amine and carboxyl groups within the p(LysAA) brushes, this approach provides a platform for integrating bioactive molecules to further mitigate the thrombotic risk.