An Oral Mucosa‐Inspired Wet‐Adhesion Janus Hydrogel With Asymmetric Bifunctionalities of Antifouling/Antioxidant for Treating Oral Ulcer in Diabetes

ABSTRACT Highly wet, dynamic, inflammatory, and fouling environments were significant challenges in the healing of diabetic oral ulcers. Inspired by the oral mucosa, a wet‐adhesion Janus hydrogel (WAJH) with asymmetric bifunctionalities of antifouling/antioxidant was proposed for diabetic oral ulcer treatment. In the WAJH, the antifouling layer was composed of the agar/polyacrylamide double‐network (Agar/PAAm DN) hydrogel, and the wet‐adhesive layer was constructed by the poly(acrylic acid‐co‐2‐phenoxyethyl acrylate)/tannic acid (PAEA/TA) hydrogel. The antifouling layer mimicked the oral epithelium to prevent pollutant invasion, and the adhesive layer imitated the basement membrane of oral mucosa to adhere firmly to wet diabetic oral ulcers. Importantly, the adhesion energies of the two layers were distinctly different, measuring 15 J m ⁻² for the antifouling layer and 316 J m ⁻² for the adhesive layer, respectively. Notably, TA not only significantly enhanced the toughness and wet adhesion but also endowed the WAJH with reactive oxygen species (ROS) scavenging and antioxidant capabilities. The WAJH remarkably accelerated the healing of oral ulcer by inhibiting inflammation at the ulcer, promoting angiogenesis, and promoting re‐epithelialization in vivo. Consequently, the WAJH with antifouling and antioxidant exhibited promising prospects in the clinical treatment of diabetic oral ulcer.