Degradable biomimetic stent with hydrogel and directional TGF-loaded nano-fiber membrane for the treatment of esophageal fistula.

Abstract

Esophageal fistulas (EFs) arising from esophageal cancer, trauma, or iatrogenic injury can lead to severe complications. While covered metal stents can effectively occlude EFs, their long-term implantation may result in migration, in-stent stenosis, and bleeding. Biodegradable covered stents offer temporary support followed by self-degradation to circumvent permanent implantation risks, therefore can act as local biotherapeutic platforms. We have developed a novel biodegradable, biomimetic stent composed of polydioxanone with a hydrogel coating and oriented, TGF-β1-loaded nanofiber membrane. It provides up to 6.92 N of radial support force and maintains integrity for 30 days. Employing microsol oriented electrospinning technology, TGF-β1-loaded nanofibers are applied to the stent's surface, not only occluding the EF but also creating a directional matrix for stem cell migration and tissue repair. Additionally, GelMA laden with autologous BMSCs encapsulates the PLGA nanofibers, with BMSCs showing oriented growth and differentiation into myoblasts upon TGF-β1 stimulation. In a rabbit EF model, this biomimetic esophageal stent significantly lowered fistula incidence. Esophagography and histopathological assessments revealed complete EF occlusion in 78 % of subjects. These findings suggest that our biomimetic esophageal stent not only supports and seals the esophagus but also promotes self-repair and tissue regeneration, advancing the application of biodegradable stents for EF treatment.