An ultrasound-responsive lipoic acid-based bioadhesive for oral mucosal wound repair

Oral mucosal wound repair remains a crucial clinical challenge, as the humid and highly dynamic oral microenvironment creates complex conditions that limit the efficacy of conventional treatment strategies. Bioadhesives have emerged as promising biomaterials that effectively address the key limitations of conventional treatments and open new avenues for oral mucosal wound repair. Herein, an ultrasound-responsive lipoic acid-based bioadhesive with in situ polymerization and targeted adhesion capabilities for oral mucosal wounds has been designed. Lipoic acid (LA) was used as the monomer and dissolved in tris(hydroxymethyl) aminomethane (Tris) solution to prepare the hydrogel precursor. Due to the unique disulfide five-membered ring in LA, the precursor rapidly gelled in situ under ultrasound stimulation after being injected onto oral wounds, ensuring precise and stable adhesion. The results demonstrated that the ultrasound-responsive polylipoic acid (UPLA) hydrogel exhibited appropriate adhesive strength and mechanical properties, while cell experiments indicated that this material possessed satisfactory biocompatibility and could promote the migration of human oral keratinocytes (HOKs). In vivo animal experiments further showed that the hydrogel achieved reliable adhesion to the rat oral mucosa and significantly accelerated wound healing processes. Notably, this therapeutic effect was attributed to the hydrogel's ability to promote epithelial regeneration and restoration of epithelial integrity, while simultaneously reducing local inflammatory responses at the wound site. This UPLA bioadhesive integrates in situ gelation, stable mucosal adhesion, and active wound-healing promotion, thereby providing a novel and promising candidate material for clinical oral mucosal wound repair.