An injectable tough hydrogel sealant enabling rapid hemostasis and promoting oral tissue regeneration

Repair of oral soft-tissue injuries remains challenging due to the moist, bacteria-rich, and mechanically active oral environment, as well as the limitations of current sealants in wet adhesion, mechanical strength, biocompatibility, bioactivity, and sealing durability. Here, we report an injectable hydrogel sealant (PAG) composed of tetra-armed poly(ethylene glycol) succinimidyl succinate and amine-functionalized gelatin, which rapidly forms in situ via NHS-amine coupling without external triggers. The optimized formulation undergoes gelation within seconds and exhibits robust mechanical properties, as well as superior adhesive strength and burst pressure compared with commercial fibrin glue. PAG demonstrates excellent cytocompatibility, hemocompatibility, and biodegradability, while promoting fibroblast proliferation in vitro. In vivo, it enables rapid hemostasis within 3 s and effective tissue repair in an acute rat tongue perforation model, markedly outperforming suture, gelatin sponge, and fibrin glue controls. Moreover, PAG effectively protects early-stage wounds and accelerates repair in both rat and porcine oral mucosal defect models. Mechanistic studies indicate that PAG establishes a pro-regenerative microenvironment by attenuating excessive inflammation, enhancing angiogenesis, and promoting M2-dominant macrophage polarization. Collectively, these findings demonstrate that the engineered PAG hydrogel enables rapid, sutureless sealing and repair of oral soft-tissue wounds, highlighting its translational potential.