Durable endothelium-mimicking coating for surface bioengineering cardiovascular stents

Mimicking the nitric oxide(NO)-release and glycocalyx functions of native vascular endothelium on cardiovascular stent surfaces has been demonstrated to reduce in-stent restenosis(ISR)effectively.However,the practical performance of such an endothelium-mimicking surfaces is strictly limited by the durability of both NO release and bioactivity of the glycocalyx component.Herein,we present a mussel-inspired amine-bearing adhesive coating able to firmly tether the NO-generating species(e.g.,Cu-DOTA coordination complex)and glycocalyx-like component(e.g.,heparin)to create a durable endothelium-mimicking surface.The stent surface was firstly coated with polydopamine(pDA),followed by a surface chemical cross-link with polyamine(pAM)to form a durable pAMDA coating.Using a stepwise grafting strategy,Cu-DOTA and heparin were covalently grafted on the pAMDA-coated stent based on carbodiimide chemistry.Owing to both the high chemical stability of the pAMDA coating and covalent immobilization manner of the molecules,this proposed strategy could provide 62.4%bioactivity retention ratio of heparin,meanwhile persistently generate NO at physiological level from 5.9±0.3 to 4.8±0.4×10^(-10) mol cm^(-2) min^(-1) in 1 month.As a result,the functionalized vascular stent showed long-term endothelium-mimicking physiological effects on inhibition of thrombosis,inflammation,and intimal hyperplasia,enhanced re-endothelialization,and hence efficiently reduced ISR.