Triamcinolone acetonide-loaded chitosan-polyethylene glycol hydrogel for preventing esophageal stricture post-endoscopic submucosal dissection

Abstract Postoperative esophageal stricture remains a significant challenge following endoscopic submucosal dissection (ESD), with limited effective prophylactic options in clinic. Here, we report the development of an injectable and tissue-adhesive hydrogel drug delivery system composed of quaternary ammonium chitosan and polyethylene glycol (QCS-PEG), which was loaded with triamcinolone acetonide (QCS-PEG@TA), designed to mitigate post-ESD strictures. In vitro assays demonstrated that the hydrogel formulation modulated macrophage polarization and inhibited fibroblast migration. In an ESD-induced porcine esophageal stricture model, treatment with drug-encapsulated hydrogel efficiently suppressed esophageal stricture and promoted tissue repair, which were superior over drug or hydrogel alone. Histological and immunohistochemical analyses revealed that the administration of hydrogel formulation reduced fibrosis and inflammatory cell infiltration in esophageal tissues. These findings suggest that QCS-PEG@TA hydrogel provides mechanical support, inflammation-modulatory and pro-healing effects that collectively prevent stricture formation, offering a clinically translatable approach to improve therapeutic outcomes after ESD.