Engineered exosomes with enriched miR-23b suppress the progression of periodontitis by reprogramming macrophages.

Periodontitis is a prevalent inflammatory disease that damages the tooth-supporting structure, leading to tooth instability and loss. Conventional therapies target biofilms but fail to address immune dysregulation, highlighting the need of host-modulating strategies. Herein, the decreased miR-23b level was found to be associated with the progression of periodontitis and identified as a potential therapeutic agent for the disease. Since the conventional methods of loading exogenous miRNAs into exosomes may impair the membrane structure, a miR-23b-overexpressed HEK293T cell line was constructed to produce engineered exosomes with enriched miR-23b (namely miR-23b-Exo). The miR-23b-Exo modulated the NF-κB signaling pathway in macrophages, thereby promoting the M2 polarization and suppressing the release of inflammatory cytokines to execute the anti-inflammatory effect. In rats with periodontitis, miR-23b-Exo alleviated the inflammation-induced periodontal damage, exhibiting favorable anti-periodontitis efficacy. Our study provides a promising host-modulating strategy based on the engineered exosomes-mediated miR-23b delivery, thereby alleviating periodontal damage by reprogramming macrophages.