title: Promoting endothelial recovery and reducing neointimal hyperplasia using sequential-like release of acetylsalicylic acid and paclitaxel-loaded biodegradable stents.
abstract: BACKGROUND
  This work reports on the development of a biodegradable dual-drug-eluting stent with sequential-like and sustainable drug-release of anti-platelet acetylsalicylic acid and anti-smooth muscle cell (SMC) proliferative paclitaxel.
  
  
  METHODS
  To fabricate the biodegradable stents, poly-L-lactide strips are first cut from a solvent-casted film. They are rolled onto the surface of a metal pin to form spiral stents. The stents are then consecutively covered by acetylsalicylic acid and paclitaxel-loaded polylactide-polyglycolide nanofibers via electrospinning.
  
  
  RESULTS
  Biodegradable stents exhibit mechanical properties that are superior to those of metallic stents. Biodegradable stents sequentially release high concentrations of acetylsalicylic acid and paclitaxel for more than 30 and 60 days, respectively. In vitro, the eluted drugs promote endothelial cell numbers on days 3 and 7, and reduce the proliferation of SMCs in weeks 2, 4, and 8. The stents markedly inhibit the adhesion of platelets on days 3, 7, and 14 relative to a non-drug-eluting stent. In vivo, the implanted stent is intact, and no stent thrombosis is observed in the stent-implanted vessels without the administration of daily oral acetylsalicylic acid. Promotion of endothelial recovery and inhibition of neointimal hyperplasia are also observed on the stented vessels.
  
  
  CONCLUSIONS
  The work demonstrates the efficiency and safety of the biodegradable dual-drug-eluting stents with sequential and sustainable drug release to diseased arteries.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital-Linkou, 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: Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Chia-Ying
authors.initials: CY
authors.lastname: Yu
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital-Linkou, Tao-Yuan, Taiwan.
authors.forename: Shang-Hung
authors.initials: SH
authors.lastname: Chang
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital-Linkou, Tao-Yuan, Taiwan.
authors.forename: Kuo-Chun
authors.initials: KC
authors.lastname: Hung
authors.affiliation: Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan.
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, 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, 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, Tao-Yuan, Taiwan.
authors.forename: Yu-Shien
authors.initials: YS
authors.lastname: Ko
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital-Linkou, Tao-Yuan, Taiwan.
authors.forename: Ming-Shien
authors.initials: MS
authors.lastname: Wen
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism / Q000601:surgery; D001241:Aspirin / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001672:Biocompatible Materials; D002135:Calcium-Binding Proteins / Q000378:metabolism; D054855:Drug-Eluting Stents; D055664:Electrochemical Techniques; D006965:Hyperplasia; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D036103:Nanotechnology; D017239:Paclitaxel / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D010973:Platelet Adhesiveness / Q000187:drug effects; D011091:Polyesters / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011817:Rabbits; D000096985:Calponins
chemical_list: D001241:Aspirin; D001672:Biocompatible Materials; D002135:Calcium-Binding Proteins; D019344:Lactic Acid; D008840:Microfilament Proteins; D017239:Paclitaxel; D011091:Polyesters; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D000096985:Calponins; C033616:poly(lactide)
keywords: biodegradable drug-eluting stents; mechanical properties; poly-L-lactide; polylactide-polyglycolide; sequential-like and sustainable release