Biocompatible, adhesive and stable GelMAc/PVAMA/MPDA@Cur hydrogels regulate immune response to improve endoscopic submucosal dissection-induced gastric ulcer healing in vivo

Endoscopic submucosal dissection (ESD) is one of the most important strategies for early gastrointestinal tumor treatment. However, the ideal healing of artificial ulcers produced after ESD procedure are still hard to achieve. In a gastric ulcer environment, the inherent peristole, acid condition and excessive oxidative stress seriously affect the therapeutic outcome of traditional medication. Curcumin (Cur) is a promising anti-inflammatory drug for gastric ulcer treatment, but its long-term use is still challenging. A polymer-assisted drug delivery system in gastrointestinal disease treatment is a new direction but is still at an initial stage. Herein, we report a hybrid hydrogel consisting of catechol motif-modified methacrylated gelatin (GelMAc) and methacrylated poly (vinyl alcohol) (PVAMA). GelMAc brought significant adhesive property and biocompatibility. PVAMA could effectively provide stability and mechanical strength. Moreover, mesoporous polydopamine nanoparticles were prepared as the drug carrier to load Cur via π-π stacking and hydrogen bonding interactions, and they were encapsulated in the hybrid GelMAc/PVAMA hydrogel. The prepared sample was proved to have a unique stability on gastric tissue even bearing acid (pH 2) and oxidative stress (H₂O₂) conditions. The slowly released Cur from the hydrogel was capable of inducing M2 polarization of macrophages. In an in vivo gastric ulcer model, the prepared sample remarkably improved gastric ulcer healing by curbing the pro-inflammatory response and alleviating oxidative stress. An accelerated reepithelization and angiogenesis were also observed. Thus, this study provides a promising hydrogel for the treatment of ESD-induced ulcers, which may attract more attentions to explore the deeper combination between biomaterials and gastrointestinal research.