Development of a novel prohealing stent designed to deliver sirolimus from a biodegradable abluminal matrix

Juan F. Granada, Shigenobu Inami, Michael S. Aboodi, Armando Tellez, Krzysztof Milewski, David Wallace-Bradley, Sherry Parker, Steve Rowland, Gaku Nakazawa, Marc Vorpah, Frank D. Kolodgie, Greg L. Kaluza, Martin B. Leon, Renu Virmani

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

Abstract

Background-We aimed to demonstrate that, by separating endothelial progenitor cell capture from sirolimus delivery through the application of drug to the abluminal surface of the stent, the degree of endothelialization can be enhanced. Methods and Results-Stainless steel R Stents, with biodegradable SynBiosys polymer coating with sirolimus abluminally applied and surface modified with anti-CD34 antibody were prepared at 2 dosages (low-dose sirolimus [LD-Combo, 2.5 μg sirolimus/mm] and full-dose sirolimus [Combo, 5 μg sirolimus/mm). These Combo stents and the Cypher stent (10 μg sirolimus/mm) were deployed in 98 normal porcine arteries and harvested for pharmacokinetic analysis at 0.25, 1, 3, 7, 14, 28, and 35 days. The LD-Combo stents showed faster early release (50% total dose in 72 hours) than the Combo and Cypher. At 30 days, drug release was near complete with both Combo stents, whereas 20% of drug remained on the Cypher stents. To assess efficacy, a total of 50 stents (Xience V=8, Cypher=8, Genous bioengineered R stent=6, LD-Combo=14, and Combo=14) were implanted in 18 pigs for 14 and 28 days. Optical coherence tomography was performed, and stents were harvested for histology. At 28 days, there was less neointimal thickness with Combo (0.173±0.088 mm) compared with Cypher (0.358±0.225 mm), LD-Combo (0.316±0.228 mm), and Xience V (0.305±0.252 mm; P<0.00001). Immunohistochemical analysis of endothelialization showed that Genous bioengineered R stent had the highest degree of platelet endothelial cell adhesion molecule expression (87%) followed by the Combo (75%), LD-Combo (65%), and Cypher (58%). Conclusions-Both optical coherence tomography and histology demonstrate that anti-CD34 sirolimus-eluting stents promote endothelialization while reducing neointimal formation and inflammation.

Original languageEnglish (US)
Pages (from-to)257-266
Number of pages10
JournalCirculation: Cardiovascular Interventions
Volume3
Issue number3
DOIs
StatePublished - Jun 2010

Keywords

  • Anti-CD34 antibody
  • Endothelial progenitor cell (EPC)
  • Endothelium
  • Sirolimus
  • Stents

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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