Biodegradable magnesium stents prevent esophageal stricture formation through TRPM7-JNK mediated anti-fibrotic mechanisms

Benign esophageal stricture (BES) represents a challenging clinical condition characterized by esophageal fibrosis-induced luminal narrowing. Current therapeutic approaches, including balloon dilation, scar incision, and stent placement, are hindered by significant clinical limitations. These include post-operative re-stenosis and the frequent need for repeated procedures, while stent use specifically carries risks of stent migration and the eventual necessity for secondary removal. Pure magnesium stents offer potential advantages through biodegradation properties that eliminate retrieval procedures while providing temporary mechanical support. We investigated the anti-fibrotic mechanisms of a pure magnesium (Mg) woven stent using RNA-sequencing, in vitro cultures (human esophageal fibroblasts-HEFs, human healthy esophageal epithelial cells-HHECs, and esophageal cancer cells-EC109), and in vivo rabbit corrosive injury models. To ensure clinical relevance, localized Mg 2+ concentrations were quantified post-implantation. Osmotic and pH-matched controls (NaCl) were employed to verify ion-specific effects. The transient receptor potential melastatin-seven (TRPM7) and mitogen-activated protein kinase (MAPK)/c-Jun N-terminal kinase (JNK) pathways were analyzed via Western blot, immunohistochemistry, and flow cytometry. RNA-seq identified significant MAPK-JNK pathway enrichment under high Mg 2+ exhibited dose-dependent inhibition of cell proliferation; low concentrations (20 mmol/L) were biocompatible, whereas high concentrations (≥80 mmol/L) induced significant cytotoxicity. In vivo, pure Mg stents degraded progressively (complete by day 7), effectively maintaining luminal patency and preventing stricture formation . Histology confirmed reduced inflammatory infiltration and collagen deposition compared to controls. Mechanistically, high Mg 2+ suppressed TRPM7 , activating JNK signaling to trigger fibroblast apoptosis and downregulate Bcl-2, TGF-β1, and α-SMA . Flow cytometry further validated increased apoptosis and G2/M phase cell cycle arrest . Pure magnesium stents prevent esophageal stricture formation through a novel TRPM7-JNK mediated anti-fibrotic mechanism . The localized release of high-concentration Mg 2+ effectively inhibits fibroblast proliferation and collagen deposition without compromising biocompatibility. This biodegradable approach successfully integrates temporary mechanical support with targeted molecular therapy, offering a promising retrieval-free strategy for the clinical management of benign esophageal strictures.