In vitro and in vivo evaluation of a novel polymer-free everolimus-eluting stent by nitrogen-doped titanium dioxide film deposition

Abstract

Inflammation and thrombosis are linked to the use of polymer-based drug-eluting stents (DES). The aim of this study was to develop a polymer-free everolimus (EVL)-eluting stent using nitrogen-doped titanium dioxide (N-TiO2) and verify its efficacy by in vitro and in vivo assessment in a porcine coronary model. Various analytical approaches such as scanning electron microscopy and atomic force microscopy, electron spectroscopy, Fourier transform infrared spectrometry and contact angle measurement were employed for the characterization. As a part of biocompatibility assessment, platelet adhesion and smooth muscle cell (SMC) proliferation were examined. Bare metal stent (BMS), N-TiO2 stent, everolimus-eluting N-TiO2 (N-TiO2-EVL) stent, and commercialized EVL-eluting stent (EES) were randomly placed in forty coronary arteries in twenty pigs. After four weeks of implantation, the stents were subjected to histological and quantitative analysis. The N-TiO2 film used in this study was well coated without any cracks or peeling. Surface hydrophilicity (88.8% of angle decrement) could be associated with the decrease in surface roughness post N-TiO2 deposition (37.0%). The platelet adhesion on the N-TiO2 surfaces was less than that on the BMS surface. The proliferation of SMC was suppressed in the N-TiO2-EVL group (30.2%) but not in the BMS group. In the animal study, the percent area restenosis was significantly decreased in the N-TiO2-EVL group compared to that in the BMS group. The results (BMS; 47.0 ± 11.00%, N-TiO2-EVL; 31.7 ± 10.50%, and EES; 29.1 ± 11.21%, n = 10, p < 0.05) were almost at par with those of the commercialized EVL-eluting stent. The introduction of N-TiO2 deposition during fabrication of polymer-free DES may be an efficient accessorial process for preventing in-stent restenosis and thrombosis.