Dual-Drug Injectable Hydrogel For Periodontitis Treatment

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Periodontitis is a chronic inflammatory disorder characterized by aggravated oxidative stress and progressive tissue destruction, as results of local immune dysregulation. Current clinical treatments focus on controlling bacterial infections, but remains limited efficacy due to persistent immune dysregulation. Here, we developed an injectable micelle-hydrogel hybrid containing curcumin (CUR) and glycyrrhizic acid (GL), named as CURM@GLH, for periodontitis treatment by reducing oxidative stress and regulating immune microenvironment. CUR was dissolved in melted polyethylene glycol distearate and then dispersed in aqueous medium to form micelles (CURM). Compared to CUR, CURM had improved solubility and stability, thus displayed greatly promoted antioxidative, anti-inflammatory, antibacterial, and anti-biofilm activities. CURM were encapsulated into a hydrogel self-assembled from GL and polyvinyl alcohol to obtain CURM@GLH. Experimental periodontitis were established in mouse to test their in vivo effects. Owing to the anti-inflammatory property of GL, CURM@GLH exerted the synergistic effects of CURM and GLH against immune dysregulation. CURM@GLH significantly repolarized macrophages from M1 to M2 phenotype, down-regulated the expression levels of pro-inflammatory cytokines, and meanwhile up-regulated the expression levels of anti-inflammatory cytokines. The ligature-induced periodontitis model in mouse showed that, CURM@GLH effectively alleviated oxidative stress and inflammation in periodontal tissues, thereby deminished alveolar bone resorption. The injectable CURM@GLH micelle-hydrogel hybrid combines curcumin and glycyrrhizic acid, synergistically alleviating oxidative stress and reprogramming immunity. It effectively inhibits inflammation and alveolar bone loss in periodontitis, demonstrating a potent dual-drug therapeutic strategy.

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