Injectable Thermosensitive GelMA/β-Glycerophosphate Hydrogel for Sustained Local Delivery of Metronidazole in Periodontal Therapy

Abstract

Local delivery of antimicrobial agents can improve periodontal therapy by prolonging drug residence at the infection site while limiting systemic exposure. This study developed an injectable thermosensitive GelMA/β-glycerophosphate (β-GP) hydrogel for sustained local delivery of metronidazole (MTZ). GelMA/β-GP formulations were evaluated for temperature-responsive gelation, injectability, rheological properties, swelling, degradation, drug encapsulation, and in vitro release. Antibacterial activity against Porphyromonas gingivalis and cytocompatibility toward human gingival fibroblasts were also investigated. The optimized formulation containing 10% (w/v) GelMA and 4% (w/v) β-GP exhibited a gelation temperature of 34.2±0.8°C and formed a stable gel within 4.1±0.4 min at 37°C. MTZ encapsulation efficiency was 82.6±2.8%, with 76.3±3.5% cumulative release after 168 h. The release profile was best described by the Korsmeyer–Peppas model (R²=0.987; n = 0.68±0.04), indicating predominantly diffusion-controlled release with polymer relaxation. The MTZ-loaded hydrogel showed 86.4±2.7% inhibition of P. gingivalis, while fibroblast viability remained above 94%. The optimized hydrogel demonstrated suitable thermoresponsive gelation, sustained MTZ release, antibacterial activity, and favorable preliminary cytocompatibility, supporting its potential as a localized periodontal drug-delivery platform.