Carnosine-copper chelator- modified small-diameter vascular grafts for the promotion of anticoagulation and endothelial regeneration

Thrombosis and poor endothelialization of small-diameter vascular grafts (SDVGs) remain the leading cause of frequent failure, despite current tissue-engineered vascular grafts providing a feasible strategy in clinical treatment strategies for the small-diameter (<6 mm) blood vessels in management of cardiovascular disease. Copper ions are normally used to achieve the purpose of antithrombotic because they can produce nitric oxide (NO) with the catalysis of NO donors. However, copper ions also participate in the Fenton reaction to produce reactive oxygen species (ROS), which would adversely affect vascular graft remodeling. Here carnosine, an ion-chelating agent with anti-inflammatory and antioxidant properties, was used to chelate with copper ions to synthesize carnosine-Cu (II) chelate which showed effective activity of antithrombotic, anti-inflammatory, and antioxidant. Besides, our research further demonstrated that copper ions still retain the catalytic activities for producing NO after chelating with carnosine accompanied by the production of lower levels of ROS (the average fluorescence intensity of ROS decreased from 79.69 to 7.13). Furthermore, the grafts achieved excellent patency with satisfactory endothelialization (the endothelial coverage reached 80.64 %) and significantly improved deposition of collagen and glycosaminoglycan for up to 12 weeks. In general, Car-Cu (II) modified SDVGs provided a facile approach to addressing the problems of thrombus and poor endothelialization in SDVGs for the clinic, which is significant in cardiovascular regenerative medicine