Ga³⁺-doped coenzyme-based adhesives for periodontitis treatment

Chronic periodontitis is a long-standing thorny issue for oral health, characterized primarily by the excessive production and accumulation of reactive oxygen species, pathogenic bacterial infection, and the continuous loss of alveolar bone. In the present study, a poly(lipoic acid) (PolyLA) coenzyme-based tissue adhesive (PolyLA/Arg/Ga) was developed for the treatment of periodontitis. It functions by combining the non-antibiotic antimicrobial gallium ion (Ga³⁺) with PolyLA/Arg to resist pathogenic bacteria and promote osteogenesis. The basic arginine not only stabilizes PolyLA at room temperature by forming salt-bridge hydrogen bonds with its carboxyl groups, but also serves as a co-factor, effectively regulating the release behavior of LA-based active molecules and Ga³⁺ by partially deprotonating the carboxyl groups on PolyLA. This, in turn, imparts significant antioxidant and antimicrobial properties to the adhesive. Owing to the abundance of adhesive carboxyl groups on its surface and the structural stability of the hydrophobic PolyLA skeleton within a wet environment, the PolyLA/Arg/Ga exhibits long-lasting wet-resistant adhesion properties toward biological tissues. Moreover, in vitro cell experiments and in vivo subcutaneous implantation studies demonstrate that the PolyLA/Arg/Ga adhesive has better cytocompatibility and histocompatibility. The PolyLA/Arg/Ga is explored as a tissue adhesive to treat a periodontitis model in rats. The results demonstrate that the PolyLA/Arg/Ga adhesive more effectively inhibited alveolar bone resorption and promoted periodontal tissue regeneration within 4 weeks compared to commercial patches. Thus, the simply designed yet multifunctional PolyLA/Arg/Ga bioadhesive offers an innovative approach for periodontitis management.