Promoting vascular healing using nanofibrous ticagrelor-eluting stents

Cheng-Hung Lee,1 Ming-Jer Hsieh,1 Kuo-Sheng Liu,2,3 Che-Wei Cheng,3 Shang-Hung Chang,1 Shih-Jung Liu,3,4 Chao-Jan Wang,5 Ming-Yi Hsu,5 Kuo-Chun Hung,1 Yung-Hsin Yeh,1 Wei-Jan Chen,1 I-Chang Hsieh,1 Jyuhn-Huarng Juang,6 Ming-Shien Wen1 1Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Chang Gung University College of Medicine, Tao-Yuan, Taiwan; 2Department of Cardiovascular Surgery, Chang Gung Memorial Hospital-Linkou, Tao-Yuan, Taiwan; 3Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan; 4Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan; 5Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou, Tao-Yuan, Taiwan; 6Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung University and Chang Gung Memorial Hospital, Tao-Yuan, Taiwan Objective: The current treatment of atherosclerotic coronary heart disease with limus-eluting stents can lead to incomplete endothelialization and substantial impairment of arterial healing relative to treatment with bare-metal stents. The sustained and local delivery of ticagrelor, a reversibly binding P2Y12 receptor inhibitor, using hybrid biodegradable nanofibers/stents, was developed to reduce neointimal formation and endothelial dysfunction.Methods: In this investigation, a solution of ticagrelor, poly(D,L)-lactide-co-glycolide, and hexafluoro isopropanol was electrospun to fabricate ticagrelor-eluting nanofibrous drug-eluting stents. The in vitro and in vivo ticagrelor concentrations were measured using a high-performance liquid chromatography assay. The effectiveness of ticagrelor-eluting stents was examined relative to that of sirolimus-eluting stents. Results: Adequate ticagrelor levels were detected for four weeks in vitro. Less HES5-positive labeling was found near the ticagrelor-eluting stented vessels (0.33±0.12) than close to the sirolimus-eluting stented