Growth factors-loaded stents modified with hyaluronic acid and heparin for induction of rapid and tight re-endothelialization

[Display omitted] Two different approaches of heparin immobilization for growth factor loading on Co–Cr surface. •Two conjugation methods were tried to immobilize heparin on HA-coated Co–Cr surface.•The use of DVS had the following advantages, (1) the conjugation of higher amount heparin; (2) higher cell viability; (3) higher loading level of growth factors, as compared to EDC.•VEGF and HGF immobilized on heparin-coated surface have complementary effects in aspects of capillary-like structure formation and gap junction expression. Rapid re-endothelialization of damaged vessel lining efficiently prevents restenosis and thrombosis and restores original vascular functions. In this study, we designed a novel metallic stent with a heparin-modified surface and used different methods, including 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and divinyl sulfone (DVS), to load growth factors. First we loaded heparin into a dopamine-conjugated hyaluronic acid (HA) coating to serve as a growth factor reservoir. In a second step, we took advantage of the heparin-binding domain of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) to gain advanced re-endothelialization capabilities. We demonstrated that DVS technique offered higher amount of growth factor loading. In vitro assessment also showed better capillary-like structure formation and localized gap junctions when DVS coating was employed. This study suggested that growth factor loaded stent modified by HA and heparin provided the advantage to rapid and tight restoration of endothelium.