Phenolic-amine chemistry mediated synergistic modification with polyphenols and thrombin inhibitor for combating the thrombosis and inflammation of cardiovascular stents

Antithrombogenicity, anti-inflammation, and rapid re-endothelialization are central requirements for the long-term success of cardiovascular stents. In this work, a plant-inspired phenolic-amine chemistry strategy was developed to combine the biological functions of a plant polyphenol, tannic acid (TA), and the thrombin inhibitor bivalirudin (BVLD) for tailoring the desired multiple surface functionalities of cardiovascular stents. To realize the synergistic modification of TA and BVLD on a stent surface, an amine-bearing coating of plasma polymerized allylamine was firstly prepared on the stent surface, followed by the sequential conjugation of TA and BVLD in alkaline solution based on phenolic-amine chemistry (i.e., Michael addition reaction). TA and BVLD were successfully immobilized onto the stent surface with considerable amounts of 330 ± 12 and 930 ± 80 ng/cm2, respectively. The abundant phenolic hydroxyl groups of TA imparted the stent with ability to suppress inflammation. Meanwhile, BVLD provided an antithrombogenic and endothelial-friendly microenvironment. As a result, the combined functions of the TA and BVLD facilitate the rapid stent re-endothelialization for reduced intimal hyperplasia in vivo, and may be a promising strategy to address the clinical complications associated with restenosis and late stent thrombosis.