Xience prime

Stents for implantation were chosen from first-generation DES durable polymer
based [Paclitaxel-eluting stents (PES) (Taxus, Boston Scientific Corporation,
Maple Grove, MN, USA) or Sirolimus-eluting stent (SES) (Cypher, Cordis, USA)] or
second-generation DES [Everolimus-eluting stent (EES) (Promus, Boston Scientific
Corporation; Xience, Xience Prime, Abbott Vascular, Santa Clara, CA, USA),
Zotarolimus-eluting stent (ZES) (Endeavor, Resolute, Medtronic, Minneapolis, MN,
USA), and Biolimus-eluting stent (BES) (Biolimus A9, Biosensors International,
Switzerland)].

Everolimus eluting stents (EES, n = 5, Xience Prime, 3.0 × 15 mm, Abbott Vascular, CA, strut thickness 81 µm) and customized integrin αvβ3 ligand coated stents (ICS, n = 5, 3.0 × 15 mm, strut thickness 80 µm) were randomly allocated to iliac arteries of male hypercholesterolemic New Zealand White Rabbits (n = 5) after 7 days for a duration of 12 weeks, in accordance to study 1. As coating ligand, the cyclic RGD (Arg-Gly-Asp) peptide, c(RGDfK), a highly selective ligand for the αvβ3 integrin was functionalized by the incorporation of a spacer-linker unit at the lysine residue. After plasma treatment of the stents, they were immersion coated with the functionalized peptide, c(RGDfK) Ahx Ahx 1 (4 isothiocyanatophenyl)thioureidyl, facilitating anchorage via the isothiocyanate group to the amine groups of chitosan forming a thiourea link. Prior to that, ProKinetic Energy BMS were spray-coated with chitosan-polylactide copolymer (also see supplemental material, section „Coating of stents with αvβ3 integrin ligand”). Endothelial permeability was assessed by FITC-dextran (250/500 kDa) injected 1 hour prior to euthanasia at day 91 (after 13 weeks). After euthanasia and tissue harvest, stented vessel (n = 10; 5 EES and 5 ICS) were bisected longitudinally and analysed using confocal microscopy (CM), followed by scanning and transmission electron microscopy (SEM/TEM).

A total of 15 swine (weighing 25 to 30 kg) were studied for 6 months to evaluate neointimal tissue serially following EES implantation. Two stent types were implanted: EES (Xience Prime, 3.0 × 12 mm, Abbott Vascular, Santa Clara, CA) as a target stent and BMS (Blazer, 3.0 × 13 mm, OrbusNeich, Hong Kong) as a control stent. Each stent was deployed in the left anterior descending artery or right coronary artery. At the time of stent deployment, each stent was systematically randomized to each coronary artery in each animal. Follow-up angiography with OCT was serially performed 1, 3, and 6 months after stent implantation. All animals received humane care in compliance with the Animal Welfare Act and “The Guide for the Care and Use of Laboratory Animals” formulated by the Institute of Laboratory Animal Research [8 ]. This study was approved by the local institutional animal care and use committee (Medi Kinetics, MK-IACUC: 111027-0001 and Cardiovascular Production Evaluation Center, Yonsei University College of Medicine).

Three different types of DESs were implanted into 17 mini-pigs (Japan Farm Co., Ltd., Kagoshima, Japan) (Fig. 1): DP-EESs (XIENCE Prime™; Abbott Vascular, Tokyo, Japan; n = 8), BP-SESs (Ultimaster™; Terumo Corp., Tokyo, Japan; n = 8), and BMSs (Kaname; Terumo Corp.; n = 8), with 1 of each type implanted into each pig (1 stent per vessel). The DP-EES is an everolimus-eluting stent with a uniform coating of durable fluoropolymer (polyvinylidene fluoride-co-hexafluoropropene) [26] . The BP-SES has an abluminal coating with a matrix containing sirolimus and poly (DL-lactide)-co-caprolactone [27] (link), [28] (link). The BP is completely metabolized into carbon dioxide and water within 3–4 months. The number of animals required was determined from previous work [29] (link). All animals were sacrificed at 9 months to investigate the early vascular response. The stents were then histologically examined. This study was approved and performed according to the guidelines of the Institutional Animal Care and Use Committee of R&D Headquarters at Terumo Corp.Fig. 1

Study Flow Chart. All animals underwent OFDI at either 1 or 3 months and at 9 months. After euthanasia at 9 months, stents were histologically investigated to analyze the vascular response and its maturity. One animal died before the euthanasia in each of the 2 BMS groups.