A Dynamic Wet-Adhesive Hydrogel Loaded with ROS-Responsive Liposomes for Chemotherapy-Induced Oral Mucositis Treatment

The clinical management of chemotherapy-induced oral mucositis (CIOM) remains a clinical challenge, primarily due to the moist and mechanically dynamic environment, which limits the adhesion and retention of conventional wound dressings. To address these clinical challenges, we designed a dynamic wet-adhesive hydrogel named AC-PEG-ALIP, which is composed of four-arm polyethylene glycol succinimidyl ester (Tetra-PEG-SS), amino-modified recombinant human type III collagen (rhCOL3-NH 2 ) and reactive oxygen species (ROS)-responsive Alkannin-encapsulated liposomes (Lip@Alk). The AC-PEG-ALIP hydrogel exhibited multiple therapeutic activities, including potent anti-inflammatory activity, robust antioxidant capacity, tissue-repair potential, and anti-senescent effects. Material characterization demonstrated that the material exhibited strong wet adhesion, with a maximum adhesion stretch of 160   kPa, sustained-release drug, and excellent biocompatibility. In vitro assessments confirmed the hydrogel's excellent biocompatibility. AC-PEG-ALIP enhanced HOK cell migration, achieving 75% wound closure at 24   h, and significantly decreased the expression of inflammatory cytokines (IL-1β, IL-6, TNF-α) and NF-κB by 50-70%. In vivo, AC-PEG-ALIP significantly accelerated wound healing in a rat CIOM model, reducing residual wound area to 11.03% on day 7 versus 61.41% in untreated controls. Histological analyses further revealed enhanced collagen deposition and a 2-fold increase in angiogenesis on day 3. In conclusion, the dynamic wet-adhesive hydrogel AC-PEG-ALIP provides a promising strategy for CIOM, highlighting the role of bio-interface design in mucosal drug delivery.