A dual-functional injectable hydrogel of curcumin-loaded alginate/carboxymethyl chitosan-integrated hydroxyapatite for effective periodontitis treatment via the synergistic regulation of anti-inflammation and osteogenesis coupling.

Periodontitis is a chronic inflammatory disease that ultimately leads to irreversible alveolar bone resorption. Anti-inflammatory therapeutics represent a cornerstone in periodontitis management, while the concomitant integration of promoting osteogenetic agents would be expected to achieve an enhanced therapeutic efficacy. In this study, synthetic nanosized curcumin particles (nCur) with superior biocompatibility, antioxidant, and anti-inflammatory properties were introduced into oxidized alginate and carboxymethyl chitosan (CMCS)-integrated hydroxyapatite (HAP) to obtain an injectable nCur/HAP-gel. This gel exhibited favorable injectable and self-healing properties and also showed the dual function of curcumin and bone-like HAP, which was prepared in biomimetic CMCS. In vitro experiments showed that the nCur/HAP-gel had a strong antioxidant and anti-inflammatory effect on RAW 264.7 cells and significantly promoted the osteogenic differentiation of human periodontal ligament cells (hPDLCs) under both physiological and inflammatory conditions. In the rat periodontitis model, the dual-functional nCur/HAP-gel with the synergic coupling of anti-inflammation and osteogenesis significantly inhibited the progression of inflammation and alveolar bone loss and enhanced bone regeneration. These findings suggest that the nCur/HAP-gel, with its superior antioxidant, anti-inflammatory, and regenerative capabilities, provides a promising therapeutic strategy for periodontitis.