Cascaded diffusion-driven self-reinforced adhesive hydrogels for hydrophobic tissue closure

Adipose tissue adhesion remains challenging due to the difficulty in breaking through hydrophobic energy barriers created by fatty acids and other hydrophobic compounds to form effective adipose tissue closure. Here, we developed a cascaded diffusion-driven adhesive hydrogel capable of achieving the closure of subcutaneous adipose tissues through a competitive multi-hydrogen-bonded network, which was modulated by the controllable spatiotemporal diffusion of gelatin, tea polyphenols, and nicotinamide at the adhesion interfaces. We showed that nicotinamide-triggered cascade diffusion could promote the penetration of tea polyphenols and gelatin networks into adjacent adipose tissues in a topologically entangled manner, achieving self-reinforced interfacial adhesion with a peak adhesion strength greater than 100 kPa. Further, we demonstrated that the hydrogel could effectively close subcutaneous adipose tissues in pig models and activate immune and lipid metabolism-related pathways to prevent fat liquefaction, thereby promoting wound healing and inhibiting excessive adipose tissue fibrosis. This work not only presents a new solution for clinical closure of adipose tissues, but also provides innovative ideas for developing bioactive materials with hydrophobic interface adhesion functions.