Integrated fabrication of a shape-adaptable, antioxidative composite stent for effective closure and biological repair of enteroatmospheric fistula

Enteroatmospheric fistulas (EAFs) pose significant clinical challenges due to persistent leakage, inflammation, and impaired epithelial repair. Transcriptomic analyses of fistula tissues reveal elevated oxidative stress, mitochondrial dysfunction, and barrier disruption. Current provisional closure devices lack adaptability to complex fistula anatomy and fail to provide bioactive support, limiting tissue repair. Here, we report a body-temperature-responsive shape memory polymer stent coated with a bioactive hydrogel, fabricated through an integrated process, for effective EAF closure and repair. The stent can be delivered in a compact state and self-deployed <i>in vivo</i>, ensuring minimally invasive implantation and conformal closure. The composite stent enhances epithelial cell migration, attenuates oxidative stress, and alleviates inflammation, thereby establishing a microenvironment that promotes repair. In rabbit EAF models, the composite stent effectively closed the fistula, improved nutritional status, restored epithelial integrity, reduced inflammation, and enhanced goblet cell regeneration. Transcriptomic profiling and pathway validation revealed activation of oxidative phosphorylation, HIF-1, PI3K-Akt signaling, tight junction, and mucosal immune pathways, highlighting restoration of redox balance, mitochondrial metabolism, barrier integrity, and immune defense. These findings demonstrate that integrating dynamic shape adaptability with bioactive functionality can promote both physical closure and biological repair. This strategy provides a generalizable platform for treating complex epithelial defects in gastrointestinal organs.