One‐Step Formation of Hierarchical Hydrogel Patch by Self‐Gelling and Phase Separation Promotes Oral Ulcer Treatment via One‐Sided Tissue Adhesion, Antibacterial, and Anti‐Inflammatory Properties

The therapeutic effect of traditional oral ulcer medications is limited, due to their complex synthetic routes, weak wet tissue adhesion, and poor bioactivity. To address these issues, a novel sprayable self-gelling powder composed of polyacrylic acid (PAA), quaternized chitosan (QCS) and puerarin (PUE) is developed, which can absorb saliva quickly and form a hydrogel patch in situ at the ulcer site through hydrogen bonding and ionic interactions. More importantly, this hydrogel patch undergoes phase separation under excessive flowing saliva and spontaneously converts into a hierarchical structure with a non-adhesive top PUE layer and an adhesive bottom PAA/QCS/PUE layer, avoiding unexpected adhesion between the hydrogel patch and adjacent tissues except oral ulcer site. In addition, this hierarchical hydrogel patch also exhibits excellent antibacterial and anti-inflammatory properties, as proven by the universal antibacterial performance toward multiple bacteria, high reactive oxygen species (ROS) scavenging capacity and promotion of macrophages from M1 to M2 types. Owing to the synergism among good one-sided tissue adhesion, antibacterial and anti-inflammatory properties, in vivo wound healing of rabbit oral mucosa defect can be realized efficiently using self-gelling PAA/QCS/PUE powders.