Inhibition of Periodontitis Induction Using a Stimuli-Responsive Hydrogel Carrying Naringin.

BACKGROUND: Developing a drug carrier with favorable handling characteristics that can respond to environmental changes after inflammation, such as pH changes, may be beneficial for treating periodontitis. This study aims to investigate the preclinical feasibility of using naringin, a naturally derived polymethoxylated flavonoid compound with anti-inflammatory properties, to inhibit periodontitis induction via a thermogelling and pH-responsive injectable hydrogel. METHODS: The hydrogel was made of amphipathic carboxymethyl-hexanoyl chitosan (CHC), ß-glycerol phosphate (ß-GP), and glycerol. Thermogelling and pH-responsive characteristics of the hydrogel, as well as cell viability after treatment with the hydrogel containing naringin, were evaluated in vitro. Hydrogel was subgingivally delivered when experimental periodontitis was induced in vivo, and therapeutic effect was evaluated with microcomputed tomography imaging, histology, and expression of inflammation-associated genes, including toll-like receptor (TLR)2, the receptor for advanced glycation end products (RAGE), myeloid differentiation primary response gene-88, and tumor necrosis factor (TNF)-α. RESULTS: The hydrogel was consistently fluidic at 4°C but rapidly gelled at 37°C. Release of naringin was faster at pH 5.5 to 6.5, and viability was significantly promoted by treatment with 0.85% naringin. Naringin-carrying CHC-ß-GP-glycerol hydrogel sites showed significantly reduced periodontal bone loss (P <0.05) and inflammatory infiltration (P <0.01) as well as significantly downregulated TLR2 (P <0.05), RAGE (P <0.01), and TNF-α (P <0.05) relative to the sites with experimental periodontitis alone. CONCLUSION: Naringin-carrying CHC-ß-GP-glycerol colloidal hydrogel can be used to inhibit induction of experimental periodontitis with favorable handling and inflammation-responsive characteristics.

Evaluation of 660 nm LED light irradiation on the strategies for treating experimental periodontal intrabony defects.

This study aims to investigate the therapeutic value of 660 nm light-emitting diode (LED) light irradiation on the strategies for treating experimental periodontal intrabony defects in vivo. Large-sized periodontal intrabony defects were created bilaterally on the mesial aspect of the maxillary second molars of 48 Sprague-Dawley rats, and the rats were equally divided into four treatment groups with primary wound intention (n = 6/treatment/time point), including open flap debridement alone (OD), barrier membrane alone (MB), xenograft alone (BG), and xenograft plus barrier membrane (MG). Each group received daily 0 or 10 J/cm(2) LED light irradiation. The animals were sacrificed after 1 or 4 weeks. The treatment outcome was evaluated by gross observation of wound dehiscence and healing, micro-CT imaging for osteogenesis, and histological assessments for inflammatory cell infiltration and periodontal reattachment. With LED light irradiation, the extent of wound dehiscence was reduced, wound closure was accelerated, epithelial downgrowth was prevented, inflammation was reduced, and periodontal reattachment was promoted in all treatment strategies. Significant reduction of inflammation with LED light irradiation was noted at 1 week in the groups BG and MG (p < 0.05). Osteogenesis was significantly promoted only in the group OD at both time points (p < 0.05). Our study showed that 660 nm LED light accelerates mucoperiosteal flap healing and periodontal reattachment. However, the enhancement of osteogenesis appeared to be limited while simultaneously treating with a barrier membrane or xenograft.

pH-Responsive Hydrogel With an Anti-Glycation Agent for Modulating Experimental Periodontitis.

BACKGROUND: Stimulus-responsive devices have emerged as a novel approach for local drug delivery. This study investigates the feasibility of a novel chitosan-based, pH-responsive hydrogel loaded with N-phenacylthiazolium bromide (PTB), which cleaves the crosslinks of advanced glycation end products on the extracellular matrix. METHODS: A chitosan-based hydrogel loaded with PTB was fabricated, and the in vitro release profile was evaluated within pH 5.5 to 7.4. BALB/cJ mice and Sprague-Dawley rats were used to evaluate the effects during the induction and recovery phases of periodontitis, respectively, and animals in each phase were divided into four groups: 1) no periodontitis induction; 2) ligature-induced experimental periodontitis (group PR); 3) experimental periodontitis plus hydrogel without PTB (group PH); and 4) experimental periodontitis plus hydrogel with PTB (group PP). The therapeutic effects were evaluated by microcomputed tomographic imaging of periodontal bone level (PBL) loss and histomorphometry for inflammatory cell infiltration and collagen density. RESULTS: PTB was released faster at pH 5.5 to 6.5 and consistently slower at pH 7.4. In the induction phase, PBL and inflammatory cell infiltration were significantly reduced in group PP relative to group PR, and the loss of collagen matrix was significantly reduced relative to that observed in group PH. In the recovery phase, PBL and inflammatory cell infiltration were significantly reduced, and significantly greater collagen deposition was noted in group PP relative to groups PR and PH at 4 and 14 days after silk removal. CONCLUSION: Chitosan-based, pH-responsive hydrogels loaded with PTB can retard the initiation of and facilitate the recovery from experimental periodontitis.