Preclinical evaluation of a novel abluminal surface coated sirolimus eluting stent with biodegradable polymer matrix

Abstract

Background: Second generation of drug eluting stents (DES) has attempted to improve safety using abluminal sirolimus drug delivery with biodegradable polymers matrix. The present preclinical study was designed to investigate the safety and efficacy profile of Abluminus™ stents (SES). This is a new coronary stent with sirolimus and biodegradable polymer matrix coated on abluminal stent and balloon surface.

Methods: SES were compared with two controls: bare metal stent (BMS) and BMS + polymer coated stents (PC). All devices (40 stents) were implanted in porcine coronary arteries with primary endpoint of endothelialization at 7 days and subsequent histological and morphometric evaluations at 7, 30 and 90 days.

Results: Early endothelialization at seven days was complete in all stents. Histology at 30 days revealed minimum inflammation in all groups and increased at 90 days in PC group while it was absent at 180 days. Thirty day morphometry showed significantly reduction of neointimal area in Abluminus™ (SES 0.96±0.48 mm(2); BMS 1.83±0.34 mm(2); PC 1.76±0.55 mm(2); P<0.05); after 90 days neointimal area was 1.10±0.54 mm(2) for SES; 1.92±0.36 mm(2) for BMS; and 1.94±0.48 mm(2) for PC; P<0.05). Neointimal thickness at 30 and 90 days respectively was 0.15±0.07 and 0.18±0.10 mm for SES, 0.57±0.08 and 0.61±0.09 mm for BMS and 0.52±0.09 and 0.59±0.08 mm, P<0.001 for PC group.

Conclusions: The most significant experimental evidence appears to be earlier endothelialization at 7 days for SES which led to safety of the device. Efficacy of the device was also observed by a reduced neointimal thickness and minimized inflammatory score at all follow-ups. Termination of antiplatelet at 30 days has not shown any further complications. Polymer thickness was almost in negligible amount at 180 days with no inflammation.

Keywords: Stent; abluminal; bio-degradable polymer; restenosis.

Figure 1

Schematic cross section of pre-crimped coated stent (A) normal view (B) enlarged view (C) SEM image. SEM, scanning electron microscopy.

Figure 2

Schematic illustrating device distribution.

Figure 3

In vitro drug release.

Figure 4

SEM showing endothelialization at seven days. SEM, scanning electron microscopy.

Figure 5

Histological section at low magnification marker on picture: (A) BMS at 30 days; (B) SES at 30 day; and (C) SES at 90 days. BMS, bare metal stent; SES, Abluminus™ stents.

Figure 6

Histomorphometric data plotted for 30 and 90 days comparing the three stent groups. (A) Medial area; (B) neointimal area; (C) % area stenosis; (D) neointimal thickness.

Figure 7

Histological sections at low (A) and high magnification (B) at 180 days in PC group. PC, polymer coated stents.

Figure 8

(A) Residual polymer in PC group stent at 30, 90 and 180 days; (B) granuloma (%) & intimal inflammation score. PC, polymer coated stents.