Functional hydrogels as submucosal injectable materials in therapeutic endoscopy

Therapeutic endoscopy, including endoscopic submucosal dissection (ESD), has transformed the management of early gastrointestinal (GI) cancers by enabling the resection of large and complex lesions. However, its widespread adoption remains limited by technical difficulty and the high risk of complications such as bleeding, perforation, and stricture. Submucosal injection materials (SIMs) are critical to ESD procedures as they provide mucosal elevation, but the elevation achieved by solution-based SIMs is typically short-lived due to rapid absorption or diffusion, often necessitating multiple injections during surgery. Recent advances in injectable hydrogels present a promising strategy to overcome these limitations. Owing to their tunable physicochemical and biological properties, hydrogels can prolong submucosal elevation, reduce injection force, and actively contribute to the management of complications. Preclinical investigations of two-component, thermoresponsive, and shear-thinning hydrogels have demonstrated favorable biocompatibility and compatibility with endoscopic delivery systems. Moreover, functional hydrogels engineered with hemostatic, adhesive, antifibrotic, or regenerative properties have shown potential to mitigate intraprocedural bleeding, accelerate wound healing, and prevent stricture formation. This review aims to provide a comprehensive overview of preclinical hydrogel-based SIMs, focusing on how these novel materials may reshape the tools and strategies available in advanced endoscopic practices, particularly ESD.