Polysaccharide-based hydrogels for esophageal applications: Drug delivery, endoscopic intervention, and postoperative...

Esophageal diseases, including esophageal cancer and gastroesophageal reflux disease, remain major clinical challenges because of limited therapeutic efficacy and frequent treatment-related complications. Systemic treatments often suffer from insufficient drug accumulation at the lesion site and undesirable off-target effects, whereas endoscopic submucosal dissection (ESD), despite its effectiveness for early-stage lesions, is frequently complicated by postoperative esophageal stricture. These limitations underscore the need for localized and multifunctional therapeutic strategies. Owing to their excellent injectability, tunable physicochemical properties, and favorable biocompatibility, polysaccharide-based hydrogels, including those derived from chitosan, alginate, hyaluronic acid, and cellulose, have emerged as promising biomaterials for esophageal applications. As drug delivery systems, they enable localized and sustained therapeutic delivery with stimuli-responsive release capabilities, thereby enhancing therapeutic efficacy while minimizing systemic toxicity. In ESD, these hydrogels serve not only as submucosal injection agents to provide stable and sustained mucosal elevation but also as wound dressings that facilitate tissue regeneration, inhibit excessive fibrosis, and reduce the risk of postoperative stricture. The current challenges and future directions for the clinical translation of polysaccharide hydrogel-based platforms are also discussed. Collectively, it provides a comprehensive framework for the rational design and clinical development of polysaccharide hydrogel-based platforms to address the unmet therapeutic needs of esophageal diseases.