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 x 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.

Automated summary

Research has shown that mimicking the functions of native endothelium on cardiovascular stent surfaces by releasing nitric oxide and mimicking glycocalyx can effectively reduce restenosis. A mussel-inspired amine-bearing adhesive coating has been developed to tether the NO-generating species and glycocalyx-like component, creating a durable endothelium-mimicking surface with high bioactivity retention and sustained NO generation. This strategy demonstrates long-term physiological effects on inhibiting thrombosis, inflammation, and intimal hyperplasia, enhancing re-endothelialization, and efficiently reducing restenosis.