Everolimus-Coated Laser-Cut Self-Expandable Metallic Stent Suppresses Stent-Induced Tissue Hyperplasia in a Rat Gastric Outlet

Abstract

Malignant gastric outlet obstruction is a severe complication of gastrointestinal malignancies, often treated with self-expandable metallic stents (SEMSs). However, conventional SEMSs are associated with in-stent restenosis due to granulation tissue formation. This work aims to evaluate the efficacy and safety of everolimus-coated laser-cut SEMS in suppressing stent-induced tissue hyperplasia in a rat gastric outlet model. Everolimus, a next-generation antiproliferative drug, is applied to laser-cut SEMS using ultrasonic spray coating. The mehcanical properties, drug release profiles, and surface morphology of the stents were analyzed. In vivo, 20 rats are divided into control (uncoated laser-cut SEMS) and experimental (everolimus-coated laser-cut SEMS) groups. Endoscopic and histological analyzes reveal significantly reduced granulation tissue area, submucosal fibrosis thickness, and inflammatory cell infiltration in the everolimus group compared to controls (p < 0.05). Immunohistochemical staining demonstrates decreased smooth muscle cell proliferation and increased apoptosis in the everolimus group. The drug-coated stents exhibit drug release over 30 days and maintain structural integrity without stent-related adverse events. These findings suggest that everolimus-coated laser-cut SEMS effectively suppress stent-induced tissue hyperplasia while preserving mechanical properties, indicating its potential as a therapeutic strategy for improving stent patency in the early stage after stent placement.