Lysine-doped polydopamine coating enhances antithrombogenicity and endothelialization of an electrospun aligned fibrous vascular graft

l Engineered vascular grafts need rapid endothelialization and anti-thrombosis. l Introduction of Lys accelerates dopamine polymerization via covalent crosslinking. l Lysine-doped polydopamine coating exhibits anti-thrombogenic and anti-inflammatory. l Lysine-doped polydopamine coating promotes the regeneration of endothelium in vivo. l Lysine-doped polydopamine coating may be applied to various bioinert synthetics. Accelerating in situ endothelialization while inhibiting thrombosis is critical for the success of small-caliber tissue-engineered vascular grafts (TEVGs). In this study, a lysine (Lys) doped polydopamine (PDA) coating strategy was exploited to functionalize the TEVGs for vascular tissue regeneration. Using electrospun aligned poly( L -lactide- co -caprolactone) (PLCL) fiber arrays as the demonstrating biomaterial, introduction of Lys to the dopamine polymerization process was found to promote the formation of PDA-Lys composite coating layer atop the fiber surface via Schiff base and Michael addition reactions. Such a surface functionalization remarkably improved the coating layer uniformity, wettability, and protein adsorption capacity. In vitro assessment showed that the PDA-Lys coating layer was anti-thrombogenic and anti-inflammatory, and accelerated the formation of confluent endothelial monolayer by promoting cell-fiber and cell-cell interactions. Upon implantation in a rabbit carotid artery replacement model for 3 months, the constructed TEVGs (2 mm inner diameter), with oriented fiber architecture parallel to the longitudinal axis of grafts, were confirmed to significantly suppress thrombosis and accelerate regeneration of endothelium and tunica media layer, thereby exhibiting a positive vascular remodeling and integration capability in revascularization. This study demonstrated that the lysine-doped PDA coating provided a facile and effective platform for the improvement of antithrombogenicity and endothelialization of TEVGs.