EW-7197 eluting nano-fiber covered self-expandable metallic stent to prevent granulation tissue formation in a canine urethral model

Kichang Han,Min Tae Kim,Jung-Hoon Park,Sung Gwon Gang,Deok Hee Lee,Su-Geun Yang,Jiaywei Tsauo,Ho-Young Song,Kun Yung Kim,Dae-Kee Kim,Dong-Hyun Kim,Wenguo Cui

doi:10.1371/journal.pone.0192430

Abstract

PurposeTo evaluate an EW-7197-eluting nanofiber-covered stent (NFCS) for suppressing granulation tissue formation after stent placement in a canine urethral model.Materials and methodsAll experiments were approved by the committee of animal research. A total of 12 NFCSs were placed in the proximal and distal urethras of six dogs. Dogs were divided into two groups with 3 dogs each. The control stent (CS) group received NFCSs and the drug stent (DS) group received EW-7197 (1000 μg)-eluting NFCSs. All dogs were sacrificed 8 weeks after stent placement Histologic findings of the stented urethra were compared using the Mann-Whitney U test.ResultsStent placement was technically successful in all dogs without procedure-related complications. On urethrographic analysis, the mean luminal diameter was significantly larger in the DS group than in the CS group at 4 and 8 weeks after stent placement (all p < 0.001). On histological examination, mean thicknesses of the papillary projection, thickness of submucosal fibrosis, number of epithelial layers, and degree of collagen deposition were significantly lower in the DS group than in the CS group (all p < 0.001), whereas the mean degree of inflammatory cell infiltration was not significantly different (p > 0.05).ConclusionThe EW-7197-eluting NFCS is effective and safe for suppressing granulation tissue formation after stent placement in a canine urethral model.

Highlights

Placement of a covered self-expandable stent (SEMS) is a well-established method for the treatment of luminal strictures involving various nonvascular organs [1,2,3,4,5]
Stent placement was technically successful in all dogs without procedure-related complications
The mean luminal diameter was significantly larger in the drug stent (DS) group than in the control stent (CS) group at 4 and 8 weeks after stent placement

Summary

Introduction

Placement of a covered self-expandable stent (SEMS) is a well-established method for the treatment of luminal strictures involving various nonvascular organs [1,2,3,4,5] These stents exert constant mechanical stress to the adjacent tissue, resulting in granulation tissue formation. EW-7197 is a novel oral TGF-β type-1 receptor kinase inhibitor [13,14] This drug has been shown to have strong antifibrotic properties in animals [15,16] and the development of a drug-eluting stent using EW-7197 may be an attractive alternative for suppressing granulation tissue formation after stent placement in the urethra. We have developed an EW7197-eluting nanofiber-covered stent (NFCS) We hypothesized that this stent would suppress granulation tissue formation after stent placement in the urethra. The purpose of this study was to evaluate EW-7197-eluting NFCSs for suppressing granulation tissue formation after stent placement in a canine urethral model

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Conclusion