Bakuchiol-Loaded F127/F68 Thermosensitive Hydrogel For Periodontitis Treatment

Bakuchiol (Bak), a natural compound from Psoralea corylifolia L. seeds, exhibits antibacterial, anti-inflammatory, and osteogenic properties. This study aims to develop a Bak-loaded hydrogel for periodontal treatment, integrating these multifunctional therapeutic effects. Bakuchiol's antibacterial (vs P. gingivalis via MIC/MBC/biofilm assays) and anti-inflammatory effects (IL-6/IL-8/TNF-α mRNA inhibition) were evaluated alongside osteogenic potential (ALP/ARS staining) and cytotoxicity in HGFs/hPDLCs. The optimized F127/F68@Bak hydrogel demonstrated controlled drug release and biocompatibility. In rat periodontitis models, it reduced bone loss, inflammation, and systemic toxicity, validated through Micro-CT, histopathology, and biomarker analysis. Bak exhibited dose-dependent antibacterial activity against Porphyromonas gingivalis (MIC=8 μg/ml; >80% growth inhibition) with significant biofilm disruption (P < 0.05). At 8 μg/ml, Bak showed no cytotoxicity to hPDLCs but enhanced HGFs proliferation and migration (P < 0.05). It shows the significant pro-inflammatory cytokines downregulation (IL-6/IL-8/TNF-α, P < 0.01) and osteogenic genes (ALP/RUNX2/COL-1, P < 0.05) upregulation, and accelerating mineralization. The optimized 8 μg/ml Bak was loaded into F127/F68@Bak hydrogel, demonstrating rapid 37°C-triggered gelation in 75 s, 85% sustained release over 72h, and excellent biocompatibility. In rat periodontitis models, this hydrogel reduced alveolar bone loss (CEJ-ABC, P < 0.05), promoted osteoclast activity, and decreased IL-6/TNF-α levels (P < 0.05) while maintaining systemic biosafety. The Bakuchiol thermosensitive hydrogel exhibits potent antibacterial, anti-inflammatory, and osteogenic properties for periodontal treatment.