Temperature-sensitive hydrogel containing bakuchiol for preventing alveolar bone loss

Antibiotics and antiseptic agents for treating periodontitis have side effects such as discoloration, opportunistic infection, and hepatotoxicity. A local delivery system using temperature-sensitive hydrogel containing bakuchiol obtained from a natural product was fabricated to overcome these problems. This study aimed to investigate the inhibitory effect of bakuchiol temperature-sensitive hydrogel on bone loss using a rat ligature-induced periodontitis model. Bakuchiol containing temperature-sensitive hydrogel was fabricated using poloxamer. The physical and biological characteristics (viscosity, gelation temperature, drug-releasing, antibacterial effect, and cytotoxicity) of the hydrogel were investigated. Bilateral upper molars of 8-week-old male Sprague-Dawley rats were ligated to induce periodontitis except for the Negative control group (NC). The positive control (PC) group was given a vehicle gel without bakuchiol daily, and bakuchiol gel was applied to the E1 group daily and the E3 group every three days. Animals were sacrificed after 2 weeks of ligation. Alveolar bone loss was measured by micro-CT, and the expression of inflammatory cytokine (IL-1β) was evaluated with real-time qPCR. The temperature-sensitive hydrogel could maintain a solution state at room temperature and a gel state at body temperature. Bakuchiol was released by day 10. The gel showed an antibacterial effect against P. gingivalis and no cytotoxicity. The expression level of IL-1β was decreased in the E1 and E3 groups (p<0.05). Bakuchiol containing temperature-sensitive hydrogel showed an antibacterial and anti-inflammatory effect without cytotoxicity. Also, the hydrogel reduced the alveolar bone loss in vivo. Bakuchiol containing temperature-sensitive hydrogel can be a promising candidate for improving periodontitis.