A Perioperative Hydrogel Platform for Integrated Endoscopic Submucosal Dissection Management

Endoscopic submucosal dissection (ESD), a minimally invasive procedure, is constrained by the rapid dissipation of conventional submucosal cushions and the absence of sustained postoperative therapeutic support. Herein, we develop a multifunctional hydrogel integrating mucosal elevating, sustained local analgesia, wound protection, antibacterial and antioxidant capabilities for perioperative management of ESD. The hydrogel is formed via Schiff base reactions between carboxymethyl chitosan and oxidized dextran, incorporates methylene blue for intraoperative visualization, and integrates mesoporous silica nanoparticles loaded with Bupivacaine (BUP@MSNs) to enable local sustained-release analgesia. Targeting critical limitations of conventional mucosal elevating agents, the hydrogel rapidly forms a stable submucosal cushion through in situ gelation, enhancing ESD procedural efficiency and safety while enabling immediate wound sealing and protection. Under physiological conditions, the hydrogel exhibits excellent injectability, self-healing capacity, and tissue adhesion at the lesion site. It also exerts potent antioxidant and antibacterial activities, fulfilling requirements for perioperative microenvironment modulation. Furthermore, the hydrogel delivers early postoperative analgesia that persists for over 48 h, effectively covering the peak pain phase post-ESD. Comprehensive in vitro and in vivo safety evaluations confirm its favorable biocompatibility and tolerability. Collectively, the hydrogel represents an integrated, clinically operable, and cost-effective candidate for gastrointestinal endoscopic minimally invasive therapies.