In vivo adhesion fault-tolerant coenzyme/queen bee acid nanomicelles self-crosslinked thermoresponsive adhesive hydrogel for efficient oral ulcer treatment

Bioadhesives have potential advantages over sutures and staples for wound closure, hemostasis, and in vivo dressing applications. However, the tissue adhesives reported so far typically fail to integrate an in vivo adhesion fault-tolerant mechanism with autonomous therapeutic activity. Here, we present the unprecedented development of a bioadhesive based on the coenzyme factor lipoic acid (LA), featuring an upper critical solution temperature and adhesion fault-tolerance. The in-situ ring-opening polymerization of LA triggered by aggregation in the naturally occurring sodium queen bee acid (SQBA) nanomicelles, leads to nanomicelle self-crosslinking via strong ionic hydrogen bonds, resulting in the formation of a thermoresponsive bioadhesive (PolyLA-SQBA). PolyLA-SQBA exhibits thermally switchable and reusable adhesion, forming rapid and robust adhesion on oral mucosa at physiological temperature, and detaching from the adhered tissue without residue upon cooling. Leveraging the natural bioactivity of LA and SQBA, PolyLA-SQBA demonstrates excellent biocompatibility, potent antioxidant activity, and exhibits significant inhibitory effects against common oral pathogens. With its intelligent responsiveness, efficient adhesion, and sustained release of bioactive molecules, PolyLA-SQBA effectively delivers both LA and SQBA to oral ulcer sites, reducing inflammatory cytokine levels and significantly accelerating the healing of oral ulcers.