Effect of a Non-polymer Titanium Dioxide Thin Film-Coated Stent with Heparin in a Porcine Coronary Restenosis Model

Abstract

Drug-eluting stents (DES) without polymer may overcome the defects of DES using polymer. The aim of this study was to examine the effect of the non-polymer titatanium dioxide (TiO2) thin film-coated stent with heparin in a porcine coronary overstretch restenosis model. Pigs were randomized into three groups in which the coronary arteries (18 pigs, 12 coronaries in each group) had either TiO2 filmheparin coated stent (THS, n=12), zotarolimus-eluting stent with polymer (ZES, n=12) and bare metal stent (BMS, n=12). Histopathologic analysis was performed at 28 days after stenting. There were no significant differences in the injury score [2.0 (range 1.0 to 2.0) in THS group vs. 2.0 (range 1.0 to 2.0) in ZES group vs. 2.0 (range 2.0 to 2.0) in BMS group, p=NS] among three groups. There were significant differences in the neointima area (2.9+/-0.85 mm2 in THS group vs. 2.8+/-0.10 mm2 in ZES group vs. 3.3+/-0.58 mm2 in BMS group, p<0.05), in the fibrin score [0.0 (range 0.0 to 1.0) in THS group vs. 2.0 (range 2.0 to 2.0) in ZES group vs. 0.5 (range 0.0 to 2.0) in BMS group, p<0.0001] and the inflammation score [1.0 (range 0.0-1.0) in THS group vs. 1.0 (range 1.0 to 2.0) in ZES group vs. 1.0 (range 0.75 to 1.0) in BMS group, p<0.0001] among the three groups. In-stent restenosis rate measured by micro computed tomography demonstrated similar results with percent area stenosis in histology analysis (57.7+/-13.14% in THS group vs. 58.7+/-16.44% in ZES group 64.8+/-8.56% in BMS group, p<0.05). THS is more effective to reduce neointima formation compared to BMS. Moreover, neointima suppressive effect of THS is non-inferior to commercial ZES, with lower fibrin and inflammation score in porcine coronary restenosis model.