Injectable Thermosensitive Hydrogel Containing Bakuchiol Reduces Periodontal Inflammation and Alveolar Bone Loss in a Rat Model

Abstract

This study aimed to develop and evaluate a bakuchiol-loaded thermosensitive hydrogel (BTH) as a novel local drug delivery system for the management of periodontitis. Bakuchiol, a natural phenolic compound extracted from Psoralea corylifolia, was incorporated into a hydrogel composed of poloxamers and carboxymethylcellulose. The gelation behavior, physicochemical properties, and drug release profile were analyzed. Additionally, antibacterial activity against Porphyromonas gingivalis was assessed. Cytotoxicity was evaluated in human gingival fibroblasts and RAW 264.7 cells. Anti-inflammatory effects were determined by measuring proinflammatory cytokine expression in lipopolysaccharide-stimulated RAW 264.7 macrophages. Furthermore, alveolar bone loss, cytokine expression, and histological findings were assessed in a rat model of ligature-induced periodontitis. BTH demonstrated sol–gel transition at body temperature, with sustained drug release over 15 days. Moreover, it exhibited significant antibacterial activity against P. gingivalis and was non-cytotoxic at an extract concentration of 6.25%. In vitro, it significantly downregulated inflammatory cytokines in activated macrophages. In vivo, BTH application reduced alveolar bone loss and interleukin-1β expression in gingival tissues. Histological analysis confirmed decreased inflammatory cell infiltration and alveolar bone destruction. Thus, BTH demonstrated both antibacterial and anti-inflammatory activities, exhibiting potential as a promising therapeutic strategy for localized periodontal treatment.