title: Acceleration of re-endothelialization and inhibition of neointimal formation using hybrid biodegradable nanofibrous rosuvastatin-loaded stents.
abstract: Incomplete endothelialization and neointimal hyperplasia of injured arteries can cause acute and late stent thromboses. This work develops hybrid stent/biodegradable nanofibers for the local and sustained delivery of rosuvastatin to denuded artery walls. Biodegradable nanofibers were firstly prepared by dissolving poly(D,L)-lactide-co-glycolide and rosuvastatin in 1,1,1,3,3,3-hexafluoro-2-propanol. The solution was then electrospun into nanofibrous tubes, which were mounted onto commercially available bare-metal stents. The in vitro release rates of the pharmaceuticals from the nanofibers were determined using an elution method and a high-performance liquid chromatography assay. The experimental results thus obtained suggest that the biodegradable nanofibers released high concentrations of rosuvastatin for four weeks. The effectiveness of the local delivery of rosuvastatin in reducing platelets was studied. The tissue inflammatory reaction caused by the hybrid stents that were used to treat diseased arteries was also documented. The proposed hybrid stent/biodegradable rosuvastatin-loaded nanofibers contributed substantially to the local and sustainable delivery of a high concentration of drugs to promote re-endothelialization, improve endothelial function, reduce inflammatory reaction, and inhibit neointimal formation of the injured artery. The results of this work provide insight into how patients with a high risk of stent restenosis should be treated for accelerating re-endothelialization and inhibiting neointimal hyperplasia.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Chang Gung University College of Medicine, Tao-Yuan, Taiwan; Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Cheng-Hung
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Chang Gung University College of Medicine, Tao-Yuan, Taiwan.
authors.forename: Shang-Hung
authors.initials: SH
authors.lastname: Chang
authors.affiliation: Graduate Institute of Medical Mechatronics, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Yu-Huang
authors.initials: YH
authors.lastname: Lin
authors.affiliation: Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan. Electronic address: shihjung@mail.cgu.edu.tw.
authors.forename: Shih-Jung
authors.initials: SJ
authors.lastname: Liu
authors.affiliation: Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou, Tao-Yuan, Taiwan.
authors.forename: Chao-Jan
authors.initials: CJ
authors.lastname: Wang
authors.affiliation: Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou, Tao-Yuan, Taiwan.
authors.forename: Ming-Yi
authors.initials: MY
authors.lastname: Hsu
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Chang Gung University College of Medicine, Tao-Yuan, Taiwan.
authors.forename: Kuo-Chun
authors.initials: KC
authors.lastname: Hung
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Chang Gung University College of Medicine, Tao-Yuan, Taiwan.
authors.forename: Yung-Hsin
authors.initials: YH
authors.lastname: Yeh
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Chang Gung University College of Medicine, Tao-Yuan, Taiwan.
authors.forename: Wei-Jan
authors.initials: WJ
authors.lastname: Chen
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Chang Gung University College of Medicine, Tao-Yuan, Taiwan.
authors.forename: I-Chang
authors.initials: IC
authors.lastname: Hsieh
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Chang Gung University College of Medicine, Tao-Yuan, Taiwan.
authors.forename: Ming-Shien
authors.initials: MS
authors.lastname: Wen
mesh_terms: D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D001672:Biocompatible Materials / Q000737:chemistry*; D001792:Blood Platelets / Q000187:drug effects; D024042:Collagen Type I / Q000032:analysis; D054855:Drug-Eluting Stents; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D005464:Fluorobenzenes / Q000008:administration & dosage* / Q000627:therapeutic use; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D057139:Nanofibers / Q000737:chemistry* / Q000648:ultrastructure; D058426:Neointima / Q000188:drug therapy* / Q000473:pathology; D020005:Propanols / Q000737:chemistry; D011743:Pyrimidines / Q000008:administration & dosage* / Q000627:therapeutic use; D011817:Rabbits; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000008:administration & dosage* / Q000627:therapeutic use; D006845:Hydrocarbons, Fluorinated
chemical_list: D001672:Biocompatible Materials; D024042:Collagen Type I; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D020005:Propanols; D011743:Pyrimidines; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides; C001337:hexafluoroisopropanol; D006845:Hydrocarbons, Fluorinated
keywords: Biodegradable drug-eluting nanofibers; Neointimal formation; Re-endothelinization; Release characteristics; Rosuvastatin