Fabrication and characteristics of dual functionalized vascular stent by spatio-temporal coating

Stent implantation with balloon angioplasty is a widely used treatment for coronary artery diseases. Stents have been developed from bare metal stent (BMS) to advanced forms such as drug-eluting stent (DES). However, modern DES still causes thrombosis and/or in-stent restenosis as long-term outcomes. For effective prevention of these problems, we fabricated a dual functionalized stent using spatio-temporal coating, which has two different surfaces, as a novel type of DES. Hyaluronic acid conjugated with dopamine (HA-DA) was applied to a bare cobalt-chromium (CC) stent prior to abluminal coating of sirolimus (SRL)-in-polymer such as poly(d,l-lactide). The SRL-in-polymer (P+S) coated on the abluminal surface of the HA-DA modified stent showed highly stable coating layer and prevented the crack formation after ballooning. In the blood- and cyto-compatibility tests, HA-DA coating displayed suppressive effects on adhesion and activation of platelets and maintained the cell viability and proliferation of human coronary artery endothelial cells even under the existence of SRL. In in vivo study using porcine restenosis model, the neointimal area and inflammation score of the dual functionalized stent with HA-DA and P+S were significantly reduced than those of BMS. It is expected that this novel type of DES can be effectively applied to utilize diverse anti-proliferative drugs and bioactive polymers. Statement of Significance Stents have been developed from bare metal stent to advanced forms such as drug-eluting stents (DESs). However, even DESs can still cause in-stent restenosis as long-term outcomes. This paper demonstrated a novel DES using spatio-temporal coating by dopamine-mediated hyaluronic acid coating (HA-DA) before asymmetric coating of sirolimus-in-poly(d,l-lactide) (P+S). It showed stable coating surface and prevented crack formation after ballooning. HA-DA coating also had an inhibitive effect on adhesion of platelets and maintained cell viability of endothelial cells even under the existence of sirolimus. Additionally, in vivo neointima area and inflammation score of HA-DA/P+S stent significantly decreased than those of BMS. We expected that this novel type of DES can be effectively applied to introduce diverse anti-proliferative drugs and bioactive molecules.