Bio-inspired robust, superhydrophilic and superlubric artificial vascular endothelium coating for anti-thromboinflammation on blood-contacting devices

Abstract

Thromboinflammation remains a substantial challenge that could compromise the therapeutic success of blood-contacting medical devices in clinic. Herein, we proposed a bioinspired strategy of constructing artificial vascular endothelium coating (AVEC) to block thromboinflammation, whereby sulfobetaine-based zwitterionic hydrogel was reinforced by multiple hydrogen bonds and covalently attached to the surface of blood-contacting medical catheters to recapitulate the physiological structure, mechanical character and biophysical function of endothelium. The cobblestone-like surface topographical structures of AVEC demonstrated superhydrophilicity (contact angle = 6.9°) and superlubricity (friction coefficient = 0.0017), which enabled a blood-unperturbed bioinert feature characterized by totally anti-adhesion of blood components, avoiding activation of complement system and platelets, and classical polarization of macrophages, finally inhibiting the thromboinflammatory reaction. Moreover, the multiple hydrogen bonds reinforced, covalently crosslinked and attached AVEC showed superior mechanical robustness under blood flow shear (6 L/min), extrusion (40 r/min; 60 days) or bending deformation (2000 times). Antithrombogenic property of AVEC tested on extracorporeal circulation lines in the setting of hemodialysis and cardiopulmonary bypass surgery on porcine demonstrated no adhesion and activation of platelet on the luminal surface after circulation for 8 h, which was unequivocally comparable to the commercial heparinized Bioline® product. Further, the applicability of AVEC was verified on various clinically used blood-contacting catheters with short or long service time for different indications, where no thrombus was detected on peripherally inserted central catheter (PICC) after endovascular implantation for 7 days. Collectively, the AVEC should provide a novel, safe and generalized anti-thromboinflammation strategy for diverse blood-contacting medical devices.