Histopathological comparison of biodegradable polymer and permanent polymer based sirolimus eluting stents in a porcine model of coronary stent implantation

Tobias Koppara; Michael Joner; Gerd Bayer; Kristin Steigerwald; Tobias Diener; Eric Wittchow

doi:10.1160/TH12-01-0043

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2012; 107(06): 1161-1171
DOI: 10.1160/TH12-01-0043

New Technologies, Diagnostic Tools and Drugs

Schattauer GmbH

Histopathological comparison of biodegradable polymer and permanent polymer based sirolimus eluting stents in a porcine model of coronary stent implantation

Tobias Koppara^*

¹Deutsches Herzzentrum München, Munich, Germany

,

Michael Joner^*

¹Deutsches Herzzentrum München, Munich, Germany

,

Gerd Bayer

²BIOTRONIK SE & Co. KG, Erlangen, Germany

,

Kristin Steigerwald

¹Deutsches Herzzentrum München, Munich, Germany

,

Tobias Diener

²BIOTRONIK SE & Co. KG, Erlangen, Germany

,

Eric Wittchow

²BIOTRONIK SE & Co. KG, Erlangen, Germany

› Author Affiliations

Abstract

Summary

Biodegradable stent coatings were recently introduced as a potential solution to overcome sustained inflammatory responses observed with permanent polymer-based drug-eluting stents. In a preliminary study, selected biodegradable or permanent polymer-based sirolimus-eluting stent (SES) formulations were screened for effectiveness in comparison to bare metal stents (BMS) at 28 days. Subsequently, the most favourable SES formulation was compared to commercially available SES (Cypher^TM) at 28,90 and 180 days to investigate the histopathologic response as well as tissue, blood and organ pharmacokinetics. Overlapping SES implantation was conducted to evaluate vascular healing at 28 days in this particular setting. SES with biodegradable poly (L-lactide) polymer (PLLA) or poly(lactide-co-glycolide) showed the most favourable outcome with regards to reductions in neointimal area in comparison to BMS at 28 days. The PLLA SES showed a similar reduction in neointimal area compared to Cypher^TM at 28 days, with significant greater reductions at 90 and 180 days (1.7 ± 0.7 mm² vs. 3.1 ± 1.5 mm², p=0.03 and 1.8 ± 1.2 mm² vs. 3.0 ± 1.5 mm², p=0.01, respectively). Sirolimus vascular tissue concentrations were detectable up to 90 days following implantation. Overlapping stented segments showed favourable histopathologic results with respect to fibrin deposition and endothelialisation at 28 days. In conclusion, the use of PLLA as drugeluting matrix resulted in mild inflammatory responses in the presence of effective sirolimus tissue concentrations. The greater efficacy observed at long-term follow-up in PLLA SES compared to Cypher^TM may be a multifactorial result of stent design, polymer biocompatibility and improved release kinetics.

Keywords

Porcine model - sirolimus-eluting stents - restenosis

Full Text

References

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