Curcumin-loaded Pickering emulsions with sustained antimicrobial and anti-inflammatory activity promote immunomodulation and bone regeneration in periodontitis

Periodontitis, a prevalent chronic inflammatory disease triggered by periodontal pathogens and exacerbated by the host immune response, leads to progressive destruction of the tooth-supporting tissues and ultimately tooth loss. Effective long-term treatment remains challenging, as conventional therapies often cannot simultaneously eradicate bacteria, control inflammation, and regenerate lost periodontal tissue. Here, we present an injectable curcumin-loaded Pickering emulsion (PE-CUR) as a multifaceted biomaterial-based therapy for periodontitis and investigate its therapeutic efficacy and underlying mechanisms. The Pickering emulsion formulation significantly enhances the bioavailability and therapeutic potency of curcumin. PE-CUR exhibits excellent biocompatibility and robust anti-inflammatory activity, notably scavenging reactive oxygen species (ROS). It also demonstrates potent antimicrobial effects, effectively eliminating key periodontal pathogens such as Porphyromonas gingivalis and Staphylococcus aureus. In a periodontitis model, PE-CUR treatment markedly attenuates periodontal inflammation and alveolar bone loss, indicating protection against tissue destruction. Mechanistically, PE-CUR promotes macrophage polarization toward an anti-inflammatory phenotype characterized by reduced M1-associated markers and enhanced M2-associated markers. This shift is accompanied by upregulation of anti-inflammatory cytokines and suppression of pro-inflammatory mediators, likely through modulation of the MAPK and PI3K/Akt signaling pathways. Additionally, PE-CUR inhibits osteoclast formation while promoting osteoblast activation and differentiation, thereby preserving alveolar bone and facilitating periodontal tissue regeneration. Collectively, these findings underscore the potential of PE-CUR as an innovative and comprehensive therapeutic strategy for periodontitis-one that concurrently addresses infection, inflammation, and tissue regeneration. This multi-functional approach holds promise as a novel periodontitis treatment and warrants further clinical investigation.