[Clinical effect of MB-PDT assisted initial therapy on alveolar angle absorption of lower anterior teeth].

PURPOSE: To evaluate the effect of MB-PDT assisted essential therapy on angle resorption of lower anterior alveolar bone in patients with periodontitis. METHODS: Forty patients who were diagnosed with periodontitis stage III-IV or C, lower anterior teeth alveolar bone angle resorption, and periodontal pocket depth greater than 4 mm were selected from April 2018 to October 2020 in the Department of Periodontology and Oral Mucosal Diseases, Changsha Stomatological Hospital. The patients were randomly divided into control group and experimental group with 20 cases in each group. Compared with the control group which was only managed with essential treatment, the experimental group was treated with MB-PDT on the basis of the control group. The plaque index (PLI) and gingival bleeding index (GBI) scores of the two groups were recorded before surgery and 1 and 2 weeks after surgery. Probing depth (PD) and clinical attachment level (CAL) were detected before and 6 months after surgery. Statistical analysis of the data was performed using Graphpad Prism 5 software package. RESULTS: The PLI and GBI of the experimental group were significantly lower than those of the control group at 1 and 2 weeks after operation(P＜0.05). Six months after surgery, PD and CAL levels in the experimental group were significantly lower than those in the control group (P＜0.05). CONCLUSIONS: MB-PDT adjuvant therapy has the advantages of simple operation, efficient sterilization, promotion of healing, and high safety performance. It may be a new non-surgical adjuvant treatment strategy for effective treatment of lower anterior alveolar angular resorption.

Metformin enhances the therapeutic effects of extracellular vesicles derived from human periodontal ligament stem cells on periodontitis.

Metformin has shown outstanding anti-inflammatory and osteogenic abilities. Mesenchymal stem cell-derived extracellular vesicles (EVs) reveal promising therapeutic potency by carrying various biomolecules. This study explored the effects of metformin on the therapeutic potential of EVs derived from human periodontal ligament stem cells (PDLSCs) for periodontitis. PDLSCs were cultured in osteogenic medium with or without metformin, and the supernatant was then collected separately to extract EVs and metformin-treated EVs (M-EVs). After identifying the characteristics, we evaluated the anti-inflammatory and osteogenic effects of EVs and M-EVs in vivo and in vitro. Osteogenic differentiation of PDLSCs was markedly enhanced after metformin treatment, and the effect was dramatically inhibited by GW4896, an inhibitor of EVs' secretion. Metformin significantly increased EVs' yields and improved their effects on cell proliferation, migration, and osteogenic differentiation. Moreover, metformin significantly enhanced the osteogenic ability of EVs on inflammatory PDLSCs. Animal experiments revealed that alveolar bone resorption was dramatically reduced in the EVs and M-EVs groups when compared to the periodontitis group, while the M-EVs group showed the lowest levels of alveolar bone loss. Metformin promoted the osteogenic differentiation of PDLSCs partly through EVs pathway and significantly enhanced the secretion of PDLSCs-EVs with superior pro-osteogenic and anti-inflammatory potential, thus improving EVs' therapeutic potential on periodontitis.

Supramolecular Composite Hydrogel Loaded with CaF2 Nanoparticles Promotes the Recovery of Periodontitis Bone Resorption.

Treatments to reduce periodontal inflammation and rescue periodontitis bone resorption have been of interest to researchers. Bone tissue engineering materials have been gradually used in the treatment of bone defects, but periodontal bone tissue regeneration still faces challenges. Considering the biocompatibility factor, constructing bionic scaffolds with natural extracellular matrix properties is an ideal therapeutic pathway. Based on the pathological mechanism of periodontitis, in this study, short peptide and nanometer inorganic particles were comingled to construct NapKFF-nano CaF2 supramolecular composite hydrogels with different ratios. Material characterization experiments confirmed that the composite hydrogel had suitable mechanical properties and a three-dimensional structure that can function in the resorption region of the alveolar bone and provide spaces for cell proliferation and adhesion. The release of low concentrations of fluoride and calcium ions has been shown to have positive biological effects in both in vivo and in vitro experiments. Vitro experiments confirmed that the composite hydrogel had good biocompatibility and promoted osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Microbiological experiments confirmed that the composite hydrogel inhibited the activity of periodontal pathogenic bacteria. In animal studies, composite hydrogel applied to periodontitis rats in vivo can effectively repair alveolar bone resorption. This composite hydrogel has a simple preparation method and is inexpensive to produce, yet it has antibacterial and osteogenesis-promoting incremental effects, which makes it well suited for the treatment of periodontitis bone resorption, providing a new strategy for periodontal bone tissue engineering.

Effects of novel lactoferrin peptides on LPS-induced alveolar bone destruction in a rat model.

To develop novel bovine lactoferrin (bLF) peptides targeting bLF-tumour necrosis factor (TNF) receptor-associated factor 6 (TRAF6) binding sites, we identified two peptides that could target bLF-TRAF6 binding sites using structural analysis. Moreover, another peptide that could bind to the TRAF6 dimerization area was selected from the bLF sequence. The effects of each peptide on cytokine expression in lipopolysaccharide (LPS)-stimulated osteoblasts (ST2) and on osteoclastogenesis were examined using an LPS-treated co-culture of primary bone marrow cells (BMCs) with ST2 cells and a single culture of osteoclast precursor cells (RAW-D) treated with soluble receptor activator of NF-κB ligand. Finally, the effectiveness of these peptides against LPS-induced alveolar bone destruction was assessed. Two of the three peptides significantly suppressed LPS-induced TNF-α and interleukin-1ß expression in ST2 cells. Additionally, these peptides inhibited and reversed LPS-induced receptor activator of NF-κB ligand (RANKL) upregulation and osteoprotegerin (OPG) downregulation, respectively. Furthermore, both peptides significantly reduced LPS-induced osteoclastogenesis in the BMC-ST2 co-culture and RANKL-induced osteoclastogenesis in RAW-D cells. In vivo, topical application of these peptides significantly reduced the osteoclast number by downregulating RANKL and upregulating OPG in the periodontal ligament. It is indicated that the novel bLF peptides can be used to treat periodontitis-associated bone destruction.

Eupatilin suppresses osteoclastogenesis and periodontal bone loss by inhibiting the MAPKs/Siglec-15 pathway.

Periodontitis is a widely prevalent oral disease around the world characterized by the disruption of the periodontal ligament and the subsequent development of periodontal pockets, as well as the loss of alveolar bone, and may eventually lead to tooth loss. This research aims to assess the suppressive impact of Eupatilin, a flavone obtained from Artemisia argyi, on osteoclastogenesis in vitro and periodontitis in vivo. We found that Eupatilin can efficiently obstruct the differentiation of Raw264.7 and bone marrow-derived macrophages (BMDMs) induced by RANKL, leading to the formation of mature osteoclasts. Consistently, bone slice resorption assay showed that Eupatilin significantly inhibited osteoclast-mediated bone resorption in a dose-dependent manner. Eupatilin also downregulated the expression of osteoclast-specific genes and proteins in Raw264.7 and BMDMs. RNA sequencing showed that Eupatilin notably downregulated the expression of Siglec-15. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses identified significantly enriched pathways in DEGs, including MAPK signaling pathway. And further mechanistic investigations confirmed that Eupatilin repressed MAPKs/NF-κBsignaling pathways. It was found that Siglec-15 overexpression reversed the inhibitory impact of Eupatilin on the differentiation of osteoclasts. Furthermore, activating MAPK signaling pathway reversed the downregulation of Siglec-15 and the inhibition of osteoclastogenesis by Eupatilin. To sum up, Eupatilin reduced the expression of Siglec-15 by suppressing MAPK signaling pathway, ultimately leading to the inhibition of osteoclastogenesis. Meanwhile, Eupatilin suppressed the alveolar bone resorption caused by experimentalperiodontitis in vivo. Eupatilin exhibits potential therapeutic effects in the treatment of periodontitis, rendering it a promising pharmaceutical agent.

Treatment of Unfavorable Intrabony Defects with Autogenous Bone Graft in Combination with Leukocyte- and Platelet-Rich Fibrin or Collagen Membranes: A Non-Inferiority Study.

Background and Objectives: Unfavorable intrabony defects (IBDs) are associated with the progression of periodontal disease and tooth loss. Growing scientific evidence has demonstrated the effectiveness of platelet concentrations in periodontal treatment. The aim of our study was to demonstrate the non-inferiority of an autogenous bone graft (ABG) associated with leukocyte- and platelet-rich fibrin (L-PRF) compared to ABG + Collagen Membrane in the treatment of IBDs. Material and Methods: Sixty-four patients with at least one IBD were randomly assigned to two groups: ABG+L-PRF and CM+ABG. Clinical and radiographic evaluations were performed at baseline and 12-month follow-up. Clinical attachment level (CAL), gingival recession (GR), probing pocket depth (PPD), and radiograph defect bone level (DBL) were compared between the two treatments. To evaluate the effectiveness of ABG+L-PRF, a non-inferiority margin of =1 mm (-1 mm for GR) was chosen; a second non-inferiority margin of =0.5 mm (-0.5 mm for GR) was set for clinical relevance. Results: At 12-month follow up, both treatments showed clinical and radiographic improvements. The 90% confidence intervals of the CM+ABG-L-PRF+ABG mean difference for CAL gain (-0.0564 mm [-0.316 to 0.203]), DBL gain (-0.433 mm [-0.721 to -0.145]), and PPD reduction (0.232 mm [0.015 to 0.449]) were below the 0.5 mm non-inferiority margin; the GR increase (0.255 mm [0.0645 to 0.445]) stayed above the -0.5 mm. Conclusions: the L-PRF+ABG treatment of unfavorable IBDs is non-inferior with respect to the CM+ABG therapy for CAL gain, but with a lower GR, a slightly higher PPD, and DBL gain.

NF-κB Decoy Oligodeoxynucleotide-Loaded Poly Lactic-co-glycolic Acid Nanospheres Facilitate Socket Healing in Orthodontic Tooth Movement.

Orthodontic space closure following tooth extraction is often hindered by alveolar bone deficiency. This study investigates the therapeutic use of nuclear factor-kappa B (NF-κB) decoy oligodeoxynucleotides loaded with polylactic-co-glycolic acid nanospheres (PLGA-NfDs) to mitigate alveolar bone loss during orthodontic tooth movement (OTM) following the bilateral extraction of maxillary first molars in a controlled experiment involving forty rats of OTM model with ethics approved. The decreased tendency of the OTM distance and inclination angle with increased bone volume and improved trabecular bone structure indicated minimized alveolar bone destruction. Reverse transcription-quantitative polymerase chain reaction and histomorphometric analysis demonstrated the suppression of inflammation and bone resorption by downregulating the expression of tartrate-resistant acid phosphatase, tumor necrosis factor-α, interleukin-1ß, cathepsin K, NF-κB p65, and receptor activator of NF-κB ligand while provoking periodontal regeneration by upregulating the expression of alkaline phosphatase, transforming growth factor-ß1, osteopontin, and fibroblast growth factor-2. Importantly, relative gene expression over the maxillary second molar compression side in proximity to the alveolus highlighted the pharmacological effect of intra-socket PLGA-NfD administration, as evidenced by elevated osteocalcin expression, indicative of enhanced osteocytogenesis. These findings emphasize that locally administered PLGA-NfD serves as an effective inflammatory suppressor and yields periodontal regenerative responses following tooth extraction.

Quercetin-Loaded Bioglass Injectable Hydrogel Promotes m6A Alteration of Per1 to Alleviate Oxidative Stress for Periodontal Bone Defects.

Periodontal disease ranks third among noncommunicable illnesses, behind cancer and cardiovascular disease, and is closely related to the occurrence and progression of various systemic diseases. However, elucidating the processes of periodontal disease and promoting periodontal bone regeneration remains a challenge. Here, quercetin is demonstrated to reduce the oxidative stress state of orofacial mesenchymal stem cells (OMSCs) in vitro and to affect the osteogenic growth of OMSCs through molecular mechanisms that mediate the m6A change in Per1. Nevertheless, the limited therapeutic efficacy of systemic medication and the limitations of local medication resulting from the small, moist, and highly dynamic periodontal environment make it challenging to treat periodontal tissues with medication. Herein, a biosafe injectable hydrogel drug-controlled delivery system is constructed as a bone-enhancing factory and loaded with quercetin to treat oxidative stress injury in periodontal tissues. This drug-carrying system made up of nanoscale bioglass microspheres and a light-cured injectable hydrogel, allows effective drug particle loading and cementation in the dynamic and moist periodontal environment. Furthermore, the system demonstrates the ability to stimulate OMSCs osteogenic differentiation in a Per1-dependent manner, which ultimately promotes periodontal bone repair, suggesting that this system has potential for clinical periodontal therapy.

Systemic antibiotics in the surgical treatment of peri-implantitis: A randomized placebo-controlled trial.

AIM: To study the clinical, radiographic and microbiological outcomes after surgical treatment of peri-implantitis, with or without adjunctive systemic antibiotics. MATERIALS AND METHODS: Eighty-four patients (113 implants) with peri-implantitis were randomized into three groups (A, amoxicillin and metronidazole; B, phenoxymethylpenicillin and metronidazole; or C, placebo). Treatment included resective surgery and implant surface decontamination with adjunctive antibiotics or placebo. Primary outcomes were probing pocket depth (PPD) reduction and marginal bone level (MBL) stability. Secondary outcomes were treatment success (defined as PPD ≤ 5 mm, bleeding on probing [BOP] ≤ 1site, absence of suppuration on probing [SOP] and absence of progressive bone loss of >0.5 mm), changes in BOP/SOP, mucosal recession (REC), clinical attachment level (CAL), bacterial levels and adverse events. Outcomes were evaluated for up to 12 months. The impact of potential prognostic indicators on treatment success was evaluated using multilevel logistic regression analysis. RESULTS: A total of 76 patients (104 implants) completed the study. All groups showed clinical and radiological improvements over time. Statistically significant differences were observed between groups for MBL stability (A = 97%, B = 89%, C = 76%), treatment success (A = 68%, B = 66%, C = 28%) and bacterial levels of Aggregatibacter actinomycetemcomitans and Tannerella forsythia, favouring antibiotics compared to placebo. Multiple regression identified antibiotic use as potential prognostic indicator for treatment success. Gastrointestinal disorders were the most reported adverse events in the antibiotic groups. CONCLUSIONS: Adjunctive systemic antibiotics resulted in additional improvements in MBL stability. However, the potential clinical benefits of antibiotics need to be carefully balanced against the risk of adverse events and possible antibiotic resistance.

ADJUNCTIVE ANTIBIOTICS MAY REDUCE PROBING DEPTH, INCREASE BONE LEVEL GAIN, AND CONTRIBUTE TO OVERALL SUCCESS IN PERI-IMPLANTITIS TREATMENT FOR UP TO 12 MONTHS POSTOPERATIVELY.

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Wang Y, Chen CY, Stathopoulou PG, Graham LK, Korostoff J, Chen YW. Efficacy of Antibiotics Used as an Adjunct in the Treatment of Peri-implant Mucositis and Peri-implantitis: A Systematic Review and Meta-analysis. Int J Oral Maxillofac Implants. 2022 Mar-Apr;37(2):235-249. doi:10.11607/jomi.9220. PMID: 35476853. SOURCE OF FUNDING: None. TYPE OF STUDY/DESIGN: Systematic review with meta-analysis of data.

Optimizing esthetic zone periodontal regeneration in a 1-2-wall infrabony defect using recombinant human platelet-derived growth factor BB and ß-tricalcium phosphate: A case report.

OBJECTIVE: Periodontitis is an inflammatory condition induced by subgingival bacterial dysbiosis, resulting in inflammatory-mediated destruction of tooth-supporting structures, potentially leading to the formation of infrabony defects. This case report describes the treatment of a patient who presented with a combination 1-2-wall defect on tooth 21. To maintain the residual periodontal attachment and minimize esthetic consequences, a regenerative approach was performed using recombinant human platelet-derived growth factor-BB (rh-PDGF-BB) and ß-tricalcium phosphate (ß-TCP). MATERIALS AND METHODS: At the time of postscaling/root planing reevaluation, a 34-year-old Asian male initially diagnosed with molar/incisor pattern stage III grade C periodontitis exhibited a 6-mm residual probing depth on the mesiopalatal aspect of tooth 21. Periodontal regenerative surgery was performed using rh-PDGF-BB with ß-TCP, without the use of a membrane. RESULTS: At the 1-year follow-up, a significant reduction in probing depth and radiographic evidence of bone fill were observed. Additionally, re-entry surgery for implant placement at site tooth 23 confirmed bone fill in the defect on tooth 21. CONCLUSION: These results demonstrate the efficacy of rh-PDGF-BB with ß-TCP in enhancing periodontal regeneration and support its use as a treatment option when treating poorly contained infrabony defects in the esthetic zone.

A Biodegradable Tissue Adhesive for Post-Extraction Alveolar Bone Regeneration under Ongoing Anticoagulation-A Microstructural Volumetric Analysis in a Rodent Model.

In addition to post-extraction bleeding, pronounced alveolar bone resorption is a very common complication after tooth extraction in patients undergoing anticoagulation therapy. The novel, biodegenerative, polyurethane adhesive VIVO has shown a positive effect on soft tissue regeneration and hemostasis. However, the regenerative potential of VIVO in terms of bone regeneration has not yet been explored. The present rodent study compared the post-extraction bone healing of a collagen sponge (COSP) and VIVO in the context of ongoing anticoagulation therapy. According to a split-mouth design, a total of 178 extraction sockets were generated under rivaroxaban treatment, of which 89 extraction sockets were treated with VIVO and 89 with COSP. Post-extraction bone analysis was conducted via in vivo micro-computed tomography (µCT), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDX) after 5, 10, and 90 days. During the observation time of 90 days, µCT analysis revealed that VIVO and COSP led to significant increases in both bone volume and bone density (p ≤ 0.001). SEM images of the extraction sockets treated with either VIVO or COSP showed bone regeneration in the form of lamellar bone mass. Ratios of Ca/C and Ca/P observed via EDX indicated newly formed bone matrixes in both treatments after 90 days. There were no statistical differences between treatment with VIVO or COSP. The hemostatic agents VIVO and COSP were both able to prevent pronounced bone loss, and both demonstrated a strong positive influence on the bone regeneration of the alveolar ridge post-extraction.

Isobavachin attenuates osteoclastogenesis and periodontitis-induced bone loss by inhibiting cellular iron accumulation and mitochondrial biogenesis.

As bone-resorbing cells rich in mitochondria, osteoclasts require high iron uptake to promote mitochondrial biogenesis and maintain a high-energy metabolic state for active bone resorption. Given that abnormal osteoclast formation and activation leads to imbalanced bone remodeling and osteolytic bone loss, osteoclasts may be crucial targets for treating osteolytic diseases such as periodontitis. Isobavachin (IBA), a natural flavonoid compound, has been confirmed to be an inhibitor of receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast differentiation from bone marrow-derived macrophages (BMMs). However, its effects on periodontitis-induced bone loss and the potential mechanism of its anti-osteoclastogenesis effect remain unclear. Our study demonstrated that IBA suppressed RANKL-induced osteoclastogenesis in BMMs and RAW264.7 cells and inhibited osteoclast-mediated bone resorption in vitro. Transcriptomic analysis indicated that iron homeostasis and reactive oxygen species (ROS) metabolic process were enriched among the differentially expressed genes following IBA treatment. IBA exerted its anti-osteoclastogenesis effect by inhibiting iron accumulation in osteoclasts. Mechanistically, IBA attenuated iron accumulation in RANKL-induced osteoclasts by inhibiting the mitogen-activated protein kinase (MAPK) pathway to upregulate ferroportin1 (Fpn1) expression and promote Fpn1-mediated intracellular iron efflux. We also found that IBA inhibited mitochondrial biogenesis and function, and reduced RANKL-induced ROS generation in osteoclasts. Furthermore, IBA attenuated periodontitis-induced bone loss by reducing osteoclastogenesis in vivo. Overall, these results suggest that IBA may serve as a promising therapeutic strategy for bone diseases characterized by osteoclastic bone resorption.

3-methyl-1H-indol-1-yl dimethylcarbamodithioate attenuates periodontitis through targeting MAPK signaling pathway-regulated mitochondrial function.

Periodontitis, the second most common oral disease, is primarily initiated by inflammatory responses and osteoclast differentiation, in which the MAPK signaling pathway and mitochondrial function play important roles. 3-methyl-1H-indol-1-yl dimethylcarbamodithioate (3o), a hybrid of indole and dithiocarbamate, was first synthesized by our group. It has shown anti-inflammatory activity against lipopolysaccharide-induced acute lung injury. However, it is not known if 3o can exert effects in periodontitis. In vitro study: LPS-induced macrophage inflammation initiation and a receptor activator of nuclear factor κB ligand-stimulated osteoclast differentiation model were established. Cell viability, inflammatory cytokines, osteoclast differentiation, the MAPK signaling pathway, and mitochondrial function before and after treatment with 3o were investigated. In vivo study: Alveolar bone resorption, inflammatory cytokine expression, osteoclast differentiation, and the underlying mechanisms were assessed in mice with periodontitis. Inflammatory cytokine expression and osteoclast differentiation appeared downregulated after 3o treatment. 3o inhibited the MAPK signaling pathway and restored mitochondrial function, including mitochondrial reactive oxygen species, mitochondrial membrane potential, and ATP production. Meanwhile, 3o reduced inflammation activation and bone resorption in mice with periodontitis, reflected by the decreased expression of inflammatory cytokines and osteoclasts, implying that 3o inhibited the MAPK signaling pathway and the mitochondrial oxidative DNA damage marker 8-OHdG. These results highlight the protective role of 3o in periodontitis in mice and reveal an important strategy for preventing periodontitis.

Effects of melatonin against experimentally induced apical periodontitis in rats.

Apical periodontitis is an inflammatory condition resulting from microbial invasion in the root canal system, causing periapical tissue destruction and bone resorption. This study investigated melatonin's effects, known for its antioxidant and anti-inflammatory properties, on experimentally induced apical periodontitis in rats. Three groups of rats were studied: control, apical periodontitis and apical periodontitis with melatonin treatment. Proinflammatory cytokines and enzyme levels in blood serum were measured, and micro-CT analysis assessed bone resorption. Results showed significantly elevated cytokines and enzyme levels in the apical periodontitis group compared to the control. However, in the melatonin-treated group, these levels were significantly reduced (p < 0.01-0.001). Micro-CT analysis indicated decreased periapical resorption cavity volume and surface area with melatonin treatment. This suggests that systemic melatonin administration can mitigate inflammation and reduce bone resorption in experimentally induced apical periodontitis in rats, potentially holding promise for human endodontic disease treatment pending further research.

Characterization and application of in situ curcumin/ZNP hydrogels for periodontitis treatment.

BACKGROUND: Periodontitis is a chronic inflammatory disease that occurs in tooth-supporting tissues. Controlling inflammation and alleviating periodontal tissue destruction are key factors in periodontal therapy. This study aimed to develop an in situ curcumin/zinc oxide (Cur/ZNP) hydrogel and investigate its characteristics and effectiveness in the treatment of periodontitis. METHODS: Antibacterial activity and cytotoxicity assays were performed in vitro. To evaluate the effect of the in situ Cur/ZNP hydrogel on periodontitis in vivo, an experimental periodontitis model was established in Sprague‒Dawley rats via silk ligature and inoculation of the maxillary first molar with Porphyromonas gingivalis. After one month of in situ treatment with the hydrogel, we examined the transcriptional responses of the gingiva to the Cur/ZNP hydrogel treatment and detected the alveolar bone level as well as the expression of osteocalcin (OCN) and osteoprotegerin (OPG) in the periodontal tissues of the rats. RESULTS: Cur/ZNPs had synergistic inhibitory effects on P. gingivalis and good biocompatibility. RNA sequencing of the gingiva showed that immune effector process-related genes were significantly induced by experimental periodontitis. Carcinoembryonic antigen-related cell adhesion molecule 1 (Ceacam1), which is involved in the negative regulation of bone resorption, was differentially regulated by the Cur/ZNP hydrogel but not by the Cur hydrogel or ZNP hydrogel. The Cur/ZNP hydrogel also had a stronger protective effect on alveolar bone resorption than both the Cur hydrogel and the ZNP hydrogel. CONCLUSION: The Cur/ZNP hydrogel effectively inhibited periodontal pathogenic bacteria and alleviated alveolar bone destruction while exhibiting favorable biocompatibility.

A whole-course-repair system based on ROS/glucose stimuli-responsive EGCG release and tunable mechanical property for efficient treatment of chronic periodontitis in diabetic rats.

Elevated glucose levels, multiple pro-inflammatory cytokines and the generation of excessive reactive oxygen species (ROS) are pivotal characteristics within the microenvironments of chronic periodontitis with diabetes mellitus (CPDM). Control of inflammation and modulation of immune system are required in the initial phase of CPDM treatment, while late severe periodontitis requires a suitable scaffold to promote osteogenesis, rebuild periodontal tissue and reduce alveolar bone resorption. Herein, a whole-course-repair system is introduced by an injectable hydrogel using phenylboronic acid functionalized oxidized sodium alginate (OSA-PBA) and carboxymethyl chitosan (CMC). Epigallocatechin-3-gallate (EGCG) was loaded to simultaneously adjust the mechanical property of the OSA-PBA/CMC + EGCG hydrogel (OPCE). This hydrogel has distinctive adaptability, injectability, and ROS/glucose-triggered release of EGCG, making it an ideal drug delivery carrier. As expected, OPCE hydrogel shows favourable antioxidant and anti-inflammatory properties, along with a regulatory influence on the phenotypic transition of macrophages, providing a favourable immune microenvironment. Apart from that, it provides a favourable mechanical support for osteoblast/osteoclast differentiation regulation at the late proliferation stage of periodontal regeneration. The practical therapeutic effects of OPCE hydrogels were also confirmed when applied for treating periodontitis in diabetic rats. In summary, OPCE hydrogel may be a promising whole-course-repair system for the treatment of CPDM.

Preventive effects of systemic Pistacia eurycarpa Yalt. administration on alveolar bone loss and oxidative stress in rats with experimental periodontitis.

OBJECTIVE: This study aimed to investigate the effects of systemic administration of P. eurycarpa Yalt. plant extract on alveolar bone loss and oxidative stress biomarkers in gingival tissue in a rat model of experimental periodontitis. METHODOLOGY: 32 male Wistar albino rats, weighing 200-250 g, were divided into four groups (n=8): Healthy control (HC), Experimental periodontitis control (EPC), Experimental periodontitis 400 mg/kg (EP400), Experimental periodontitis 800 mg/kg (EP800). Experimental periodontitis was induced using the ligating method. Distilled water was administered to the HC and EPC groups and the plant extract was administered to the EP400 and EP800 groups by oral gavage at doses of 400 mg/kg and 800 mg/kg, respectively. The rats were sacrificed on the 15th day. The values of glutathione peroxidase GSH-Px, malondialdehyde (MDA), superoxide dismustase (SOD), interleukin-1ß (IL-1ß), interleukin-10 (IL-10), total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI) in the gingival tissues were analyzed by ELISA tests. Alveolar bone loss was assessed using micro-CT images of the maxilla. RESULTS: Although the IL-1ß, TOS, OSI results of the healthy control group were lower than those of the other groups, the TAS values were higher (p<0.05). No significant difference was found in the biochemical parameters among the EPC, EP400, and EP800 groups (p>0.05). Alveolar bone loss was significantly reduced in the extract groups compared to the EPC group (p<0.001). CONCLUSION: Within the limitations of this study, it was observed that the systemic P. eurycarpa extract application reduced alveolar bone loss in a rat model of experimental periodontitis. Further studies are needed to elucidate the beneficial effects of P. eurycarpa.

Computational analysis of curcumin-mediated alleviation of inflammation in periodontitis patients with experimental validation in mice.

AIM: Using network pharmacology and experimental validation to explore the therapeutic efficacy and mechanism of curcumin (Cur) in periodontitis treatment. MATERIALS AND METHODS: Network pharmacology was utilized to predict target gene interactions of Cur-Periodontitis. Molecular docking was used to investigate the binding affinity of Cur for the predicted targets. A mouse model with ligature-induced periodontitis (LIP) was used to verify the therapeutic effect of Cur. Microcomputed tomography (micro-CT) was used to evaluate alveolar bone resorption, while western blotting, haematoxylin-eosin staining and immunohistochemistry were used to analyse the change in immunopathology. SYTOX Green staining was used to assess the in vitro effect of Cur in a mouse bone marrow-isolated neutrophil model exposed to lipopolysaccharide. RESULTS: Network pharmacology identified 114 potential target genes. Enrichment analysis showed that Cur can modulate the production of neutrophil extracellular traps (NETs). Molecular docking experiments suggested that Cur effectively binds to neutrophil elastase (ELANE), peptidylarginine deiminase 4 (PAD4) and cathepsin G, three enzymes involved in NETs. In LIP mice, Cur alleviated alveolar bone resorption and reduced the expression of ELANE and PAD4 in a time-dependent but dose-independent manner. Cur can directly inhibit NET formation in the cell model. CONCLUSIONS: Our research suggested that Cur may alleviate experimental periodontitis by inhibiting NET formation.

Oxytocin alleviates periodontitis in adult rats.

OBJECTIVE: The objective of the study was to evaluate the expression of oxytocin receptors in normal and inflamed gingiva, as well as the effects of systemic administration of oxytocin in bone loss and gum inflammatory mediators in a rat model of experimental periodontitis. BACKGROUND DATA: Current evidence supports the hypothesis of a disbalance between the oral microbiota and the host's immune response in the pathogenesis of periodontitis. Increased complexity of the microbial biofilm present in the periodontal pocket leads to local production of nitrogen and oxygen-reactive species, cytokines, chemokines, and other proinflammatory mediators which contribute to periodontal tissue destruction and bone loss. Oxytocin has been suggested to participate in the modulation of immune and inflammatory processes. We have previously shown that oxytocin, nitric oxide, and endocannabinoid system interact providing a mechanism of regulation for systemic inflammation. Here, we aimed at investigating not only the presence and levels of expression of oxytocin receptors on healthy and inflamed gingiva, but also the effects of oxytocin treatment on alveolar bone loss, and systemic and gum expression of inflammatory mediators involved in periodontal tissue damage using ligature-induced periodontitis. Therefore, anti-inflammatory strategies oriented at modulating the host's immune response could be valuable adjuvants to the main treatment of periodontal disease. METHODS: We used an animal model of ligature-induced periodontitis involving the placement of a linen thread (Barbour flax 100% linen suture, No. 50; size 2/0) ligature around the neck of first lower molars of adult male rats. The ligature was left in place during the entire experiment (7 days) until euthanasia. Animals with periodontitis received daily treatment with oxytocin (OXT, 1000 µg/kg, sc.) or vehicle and/or atosiban (3 mg/kg, sc.), an antagonist of oxytocin receptors. The distance between the cement-enamel junction and the alveolar bone crest was measured in stained hemimandibles in the long axis of both buccal and lingual surfaces of both inferior first molars using a caliper. TNF-α levels in plasma were determined using specific rat enzyme-linked immunosorbent assays (ELISA). OXT receptors, IL-6, IL-1ß, and TNF-α expression were determined in gingival tissues by semiquantitative or real-time PCR. RESULTS: We show that oxytocin receptors are expressed in normal and inflamed gingival tissues in male rats. We also show that the systemic administration of oxytocin prevents the experimental periodontitis-induced increased gum expression of oxytocin receptors, TNF-α, IL-6, and IL-1ß (p < .05). Furthermore, we observed a reduction in bone loss in rats treated with oxytocin in our model. CONCLUSIONS: Our results demonstrate that oxytocin is a novel and potent modulator of the gingival inflammatory process together with bone loss preventing effects in an experimental model of ligature-induced periodontitis.