title: Assessment of an asymmetrical coating stent with sirolimus released from ablumial matrix in porcine model.
abstract: BACKGROUND
  Delayed endothelialization contributes to stent thrombosis of current drug-eluting stents. The asymmetrical coating technique provides an anti-proliferative effect abluminally without affecting luminal endothelialization. Layer-by-layer self-assembled chitosan/heparin (C/H LBL) has been proved to promote re-endothelialization. A novel stent system, C/H LBL coated luminally and sirolimus released abluminally (C/H LBL-SES), was fabricated.
  
  
  METHODS
  Bare metal stents (BMS), traditionally circumferential sirolimus-eluting stents (SES), and C/H LBL-SES were implanted into porcine coronary arteries. At the 7, 14 and 28 days follow-up (FU), angiography, intravascular ultrasound (IVUS), vasomotor function induced by acetylcholine (Ach), scanning-electron microscopy and histopathology were performed. Remodeling index (RI) was based on IVUS and defined as cross-sectional area (CSA) of vessel at in-stent segment divided by CSA of reference vessel and expressed as a percentage with a normal range from 0.95 to 1.05.
  
  
  RESULTS
  Thirty-eight mini pigs were enrolled and 74 stents (BMS = 23, C/H LBL = 28, SES = 23) were implanted in this study. At 28 days after implantation, the diameter stenosis of C/H LBL-SES by quantitative coronary angiography was 18.8 ± 2.5 %, the area stenosis by histomorphometry was 24.2 ± 2.9 %, which were comparable to that of SES and superior to BMS. At 14 days, re-endothelialization of C/H LBL-SES was almost completed, while only about 50 % of surface of SES was covered by endothelium. At 7, 14 and 28 days FU, although C/H LBL-SES suffered a greater vasoconstriction induced by Ach infusion than BMS (P < 0.05), it behaved better than SES (P < 0.01). No sign of stent malapposition was detected, while RI was within the normal range by IVUS. No acute or subacute thrombotic events occurred in all three groups.
  
  
  CONCLUSIONS
  The asymmetrically designed C/H LBL-SES successfully inhibited neointima hyperplasia, while diminishing vasoconstriction after Ach-stress. Endothelialization of C/H LBL-SES was less affected compared with traditionally circumferentially coated SES.
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Li
authors.initials: L
authors.lastname: Shen
authors.forename: Yizhe
authors.initials: Y
authors.lastname: Wu
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Lingxiang
authors.initials: L
authors.lastname: Wu
authors.forename: Chao
authors.initials: C
authors.lastname: Dong
authors.forename: Yongxing
authors.initials: Y
authors.lastname: Gao
authors.forename: Aijun
authors.initials: A
authors.lastname: Sun
authors.forename: Yunzeng
authors.initials: Y
authors.lastname: Zou
authors.forename: Juying
authors.initials: J
authors.lastname: Qian
authors.forename: Jianguo
authors.initials: J
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: Zhong
authors.forename: Junbo
authors.initials: J
authors.lastname: Ge
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D048271:Chitosan; D020099:Coated Materials, Biocompatible; D017023:Coronary Angiography; D023903:Coronary Restenosis / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D054855:Drug-Eluting Stents; D042783:Endothelial Cells / Q000187:drug effects / Q000648:ultrastructure; D006493:Heparin; D006965:Hyperplasia; D008670:Metals; D008855:Microscopy, Electron, Scanning; D058426:Neointima; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects / Q000295:instrumentation*; D011474:Prosthesis Design; D020123:Sirolimus / Q000008:administration & dosage*; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors; D018084:Ultrasonography, Interventional; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D002317:Cardiovascular Agents; D020099:Coated Materials, Biocompatible; D008670:Metals; D006493:Heparin; D048271:Chitosan; D000109:Acetylcholine; D020123:Sirolimus