Epigenetic and inflammatory events in experimental periodontitis following systemic microbial challenge.

AIM: The purpose of this study was to determine inflammatory and epigenetic features following induction of oral and gut dysbiosis in experimental periodontitis in order to examine the interplay between oral and systemic infection. MATERIALS AND METHODS: Periodontitis was induced in 6- to 8-week-old C57BL/6 mice by (a) Ligature placement (Lig group) (oral challenge); (b) P. gingivalis gavage (Pg group) (systemic challenge); and (c) the combination of the two models oral and systemic challenge (Pg + Lig). The duration of the experiment was 60 days, and the animals were then sacrificed for analyses. Alveolar bone loss was assessed, and a multiplex immunoassay was performed. Maxillae and gut tissues were immunostained for DNMT3b (de novo methylation marker), B and T lymphocyte attenuator (BTLA) and IL-18R1 (inflammation markers). RESULTS: Pg and Pg + Lig groups exhibited higher bone loss when compared to Sham. BAFF, VEGF, RANKL, RANTES and IP-10 were significantly higher with Pg gavage. Likewise, DNMT3b was overexpressed in both gut and maxilla after the Pg administration. The same pattern was observed for BTLA and IL-18R1 in gut tissues. CONCLUSIONS: The systemic microbial challenge either alone or in combination with local challenge leads to distinct patterns of inflammatory and epigenetic features when compared to simply locally induced experimental periodontitis.

Effects of Bifidobacterium probiotic on the treatment of chronic periodontitis: A randomized clinical trial.

AIM: This randomized placebo-controlled clinical trial evaluated the effect of Bifidobacterium animalis subsp. lactis (B. lactis) HN019-containing probiotic lozenges as adjuvant to scaling and root planing (SRP) in patients with generalized chronic periodontitis. MATERIALS AND METHODS: Forty-one chronic periodontitis patients were recruited and monitored clinically, immunologically, and microbiologically at baseline (before SRP) and 30 and 90 days after SRP. All patients were randomly assigned to a Test (SRP + Probiotic, n = 20) or Control (SRP + Placebo, n = 21) group. The probiotic lozenges were used twice a day for 30 days. The data were statistically analysed. RESULTS: The Test group presented a decrease in probing pocket depth and a clinical attachment gain significantly higher than those of the Control group at 90 days. The Test group also demonstrated significantly fewer periodontal pathogens of red and orange complexes, as well as lower proinflammatory cytokine levels when compared to the Control group. Only the Test group showed an increase in the number of B. lactis HN019 DNA copies on subgingival biofilm at 30 and 90 days. CONCLUSION: The use of B. lactis HN019 as an adjunct to SRP promotes additional clinical, microbiological, and immunological benefits in the treatment of chronic periodontitis (NCT03408548).

Evaluation of a bone substitute covered with a collagen membrane for ridge preservation after tooth extraction. Clinical and tomographic randomized controlled study in humans.

OBJECTIVE: To evaluate the use of a synthetic bone substitute covered with a collagen membrane for ridge preservation after tooth extraction, by clinical and tomographic analysis. MATERIAL AND METHODS: Fifteen patients, presenting at least two maxillary anterior teeth indicated for extraction, were selected: in the test group (TG), post-extraction sockets were filled by a synthetic bone substitute; in the control group (CG), by blood clot. In both groups, the sockets were covered by a collagen membrane. Cone-beam computerized tomography (CBCT) scans were acquired immediately after and 6 months post-surgically, and horizontal and vertical dimensional bone changes were quantified. RESULTS: Transurgical clinical analysis presented no statistically significant differences between TG and CG (p > .05). CBCT intragroup evaluation presented statistically significant reduction for the buccal alveolar measurement (TG = 1.58 mm or 21.82%, and CG = 1.66 mm or 24.08%) and horizontal cervical measurement (TG = 0.55 mm or 8.30% and CG = 1.30 mm or 17.68%), and not significant for palatal alveolar measurement (TG = 0.44 mm or 3.42% and CG = 0.26 mm or 3.89%). For alveolar height and horizontal apical measurements, this decrease was significant only for the CG, with reductions of 1.03 mm and 0.50 mm, respectively, compared to a decrease of 0.57 mm and 0.19 mm for the TG. The intergroup analysis showed significant difference for cervical horizontal measurement after 6 months (p < .05). CONCLUSION: The results showed that the use of the bone substitute covered with a collagen membrane resulted in less changes in vertical and horizontal alveolar ridge dimensions than the collagen membrane alone.

Effect of surgical periodontal treatment associated to antimicrobial photodynamic therapy on chronic periodontitis: A randomized controlled clinical trial.

AIM: This randomized controlled clinical trial evaluated the effects of an adjunctive single application of antimicrobial photodynamic therapy (aPDT) in Surgical Periodontal Treatment (ST) in patients with severe chronic periodontitis (SCP). MATERIAL AND METHODS: In a split-mouth design, 20 patients with SCP were treated with aPDT+ST (Test Group, TG) or ST only (Control Group, CG). aPDT was applied in a single episode, using a diode laser and a phenothiazine photosensitizer. All patients were monitored until 90 days after surgical therapy. Levels of 40 subgingival species were measured by checkerboard DNA-DNA hybridization at baseline, 60 and 150 days. Clinical and microbiological parameters were evaluated. RESULTS: In deep periodontal pockets depth (PPD ≥5 mm), Test Group presented a significantly higher decrease in PPD than Control Group at 90 days after surgical therapy (p < .05). Test Group also demonstrated significantly less periodontal pathogens of red complex (Treponema denticola) (p < .05). CONCLUSION: A single episode of aPDT used in adjunct to open flap debridement of the root surface in the surgical treatment of SCP: i) significantly improved clinical periodontal parameters; ii) eliminates periodontal pathogens of the red complex more effectively (NCT02734784).

Antimicrobial photodynamic therapy as an alternative to systemic antibiotics: results from a double-blind, randomized, placebo-controlled, clinical study on type 2 diabetics.

AIM: This double-blind, placebo-controlled clinical study compared multiple applications of the antimicrobial photodynamic therapy (aPDT) treatment protocol, to systemic doxycycline as adjuvant to scaling and root planing (SRP) on type 2 diabetic patients on clinical, systemic and immune-inflammatory outcomes. MATERIALS AND METHODS: Thirty patients with Hba1c >7% were allocated in two groups, SRP + Doxy (n = 15) using systemic doxycycline 100 mg/day (14 days) and SRP + aPDT (n = 15) with multiple applications (0, 3, 7 and 14 days). Primary outcome was glycated haemoglobin levels (HbA1c). Clinical parameters: plaque score (PS), bleeding on probe, probing depth, suppuration, gingival recession, and clinical attachment level, percentage of pockets with desired clinical endpoint were measured at baseline and 3 months after therapy. Cytokine profile was assessed at 0, 1 and 3 month to measure IL1-ß, TNF-α and TGF-ß on gingival crevicular fluid. RESULTS: No significant difference was detected on HbA1c, between treatments. The SRP + aPDT group showed advantage on reducing moderate pockets in single-rooted teeth at 3 months. SRP + aPDT presented better results at 3 months on IL1-ß levels. There were no significant differences between TNF-α and TGF-ß. CONCLUSIONS: Both treatments improved clinical and systemic outcomes (Hba1c). SRP + aPDT performed better in moderate probing pocket depth on single-rooted teeth, reduced favourably inflammation in short term, and may be an alternative to systemic antibiotics. (Clinicaltrials.org ID NCT01595594).

Influence of periodontal tissue thickness on buccal plate remodelling on immediate implants with xenograft.

AIM: To evaluate the influence of gingival thickness and bone grafting on buccal bone plate remodelling after immediate implant placement in sockets with thin buccal bone, using a flapless approach. MATERIALS AND METHODS: The gingiva of eight dogs was thinned at one side of the mandible, mandibular premolars were extracted without flaps, and four implants were installed on each side at 1.5 mm from the buccal bone. The sites were randomly assigned into: TG (test group) = thin gingiva; TG + GM (TG with grafting material); CG (control group) = normal gingiva; and CG + GM (CG with grafting material). After 12 weeks the dogs were sacrificed and the samples were processed for histological analysis. RESULTS: All animals exhibited a thin buccal bone initially. In all the experimental groups the buccal gap was filled with newly formed bone and the buccal bone level was slightly apical to the implant shoulder. There were no statistically significant differences among the groups for the histomorphometric parameters. CONCLUSIONS: The thickness of the buccal bone was a fundamental factor in buccal bone plate resorption, even with flapless implantation. The gingival thickness or the addition of a biomaterial in the gap did not influence the results.

The influence of the periodontal biotype on peri-implant tissues around immediate implants with and without xenografts. Clinical and micro-computerized tomographic study in small Beagle dogs.

OBJECTIVE: Soft tissues and buccal bone plate remodeling after immediate implantation in sockets with thin buccal bone, using the flapless approach with or without bone graft into the buccal gap, was compared between sites with thin and normal gingiva. MATERIAL AND METHODS: Eight dogs had the gingiva of one side of the mandible thinned, the mandibular premolars were extracted without flaps, and 4 implants were installed in each side, positioned 1.5 mm from the buccal bone. The sites were randomly assigned into: TG (test group) = thin gingiva; TG + GM (TG with grafting material); CG (control group) = normal gingiva; and CG + GM (CG with grafting material). Buccal bone thickness (BBT), thickness of keratinized tissue (TKT), alveolar thickness (AT), gingival recession (GR), and probing depth (PD) were clinically evaluated. Within 12 weeks the dogs were sacrificed and the samples were analyzed by micro-computerized tomography. RESULTS: A thin BBT was observed in all the dogs. The presurgical procedures reduced TKT in the test group, with minimal changes of the AT. There were no statistically significant differences among the groups for the clinical parameters and the tomographic analysis showed similar linear and tri-dimensional bone reduction in all the groups. CONCLUSION: The thickness of the buccal bone was a fundamental factor in buccal bone plate resorption, even with flapless implantation. The decrease in gingival thickness or the addition of a biomaterial in the gap did not influence the results.

Adjunctive effect of antimicrobial photodynamic therapy to nonsurgical periodontal treatment in smokers: a randomized clinical trial.

The aim of this study was to investigate the adjunctive effect of antimicrobial photodynamic therapy (aPDT) to scaling and root planing (SRP) in smokers with chronic periodontitis. Twenty subjects had two contralateral teeth randomly assigned to receive SRP (SRP group) or SRP + a single episode of aPDT (SRP + aPDT group), with a diode laser and a phenothiazine photosensitizer. Plaque index, bleeding on probing, probing depth (PD), clinical attachment level (CAL), and gingival recession were recorded, and gingival crevicular fluid was collected for assay of IL-1ß and matrix metalloproteinase (MMP)-8 levels. There was a significant PD reduction (SRP 1.81 ± 0.52 mm/SRP + aPDT 1.58 ± 1.28 mm; p < 0.001) and a significant CAL gain (SRP 1.60 ± 0.92 mm/SRP + aPDT 1.41 ± 1.58 mm; p < 0.001) for both groups. Significant differences were not observed in between-group comparisons. IL-1ß level in gingival crevicular fluid was higher in SRP group after 1 week (SRP 24.65 ± 18.85 pg/µL/SRP + aPDT 34.07 ± 24.81 pg/µL; p = 0.048), and MMP-8 level was higher in SRP group after 12 weeks (SRP 303.31 ± 331.62 pg/µL/SRP + aPDT 534.23 ± 647.37 pg/µL; p = 0.024). There were no statistically significant differences in intragroup comparisons. The adjunctive effect of aPDT did not warrant improvements on clinical parameters in smokers. However, it resulted in a suppression of IL-1ß and MMP-8 when compared with SRP alone.

Additional effects of aPDT on nonsurgical periodontal treatment with doxycycline in type II diabetes: a randomized, controlled clinical trial.

The association of doxycycline and periodontal treatment in non-controlled diabetes mellitus (DM) has shown positive results on clinical and metabolic parameters. Antimicrobial photodynamic therapy (aPDT) is a local and painless antimicrobial treatment that can be applied in periodontal treatment without systemic risks. The aim of this study was to evaluate the potential improvement of aPDT on clinical and metabolic effects in patients with type 2 diabetes mellitus in conjunction with nonsurgical periodontal treatment plus doxycycline. Thirty patients with type 2 diabetes and diagnosis of chronic periodontitis were treated with scaling and root planning (SRP; N = 15) or SRP plus phenothiazine chloride photosensitizer-induced aPDT (SRP + aPDT, N = 15). Patients of both groups took doxycycline (100 mg/day) for 2 weeks and plaque index, bleeding on probe (BOP), probing pocket depth (PPD), suppuration, clinical attachment level (CAL), and glycated hemoglobin levels (HbA1c) were measured at baseline and 3 months after therapy. An improvement in clinical parameters such as PPD, CAL, S, and BOP between groups was observed but without statistical significance (p > 0.05). Intragroup analysis showed a significant reduction of HbA1c (8.5 ± 0.9 to 7.5 ± 0.1, p < 0.01) in the SRP + aPDT group. The differences of HbA1c between baseline and 3 months were greater for the SRP + aPDT (11.4 %) than SRP (10 %) (0.87 ± 0.9 and 0.4 ± 0.84 respectively; p < 0.05). A single application of the aPDT as an adjunct to periodontal treatment did not show additional benefits in the clinical parameters but resulted in a slight greater decrease in HbA1c.

Buccal bone remodeling after tooth extraction using the flapless approach with and without synthetic bone grafting. A histomorphometric study in dogs.

OBJECTIVE: The aim of this study was to evaluate buccal bone remodeling of fresh sockets following tooth extraction using the flapless approach, with or without synthetic graft materials. MATERIAL AND METHODS: Eight dogs had the mandibular bicuspids extracted without flaps, and two alveoli on each side (total of 4) were selected. The following groups were devised: one socket on each side received a grafting material (test group), and the other remained only with a blood clot (control group). Ground sections were prepared from 12-week healing biopsies, and histomorphometry was performed. RESULTS: The buccal crest level (BCL) relative to the new bone (i), in the test group, showed numerically better data when compared with the control group, but without statistical relevance. The BCL relative to the old bone (ii) was very similar for the groups without statistical relevance. The alveolar ridge width (ARW) showed similar results without statistically significant difference between the groups. The total bone area (TBA) showed statistically significant differences between the test (38.60%) and control (47.18%) groups. The new bone area (NBA) presents a numerical difference between the test (15.62%) and control (22.24%), but without statistically significant differences. The old bone and the bone marrow were similar for both groups. CONCLUSION: It was observed that there was no loss of the buccal bone crest in relation to the lingual bone crest, especially in the test group.

Chronological analysis of periodontal bone loss in experimental periodontitis in mice.

OBJECTIVES: Periodontal disease is understood to be a result of dysbiotic interactions between the host and the biofilm, causing a unique reaction for each individual, which in turn characterizes their susceptibility. The objective of this study was to chronologically evaluate periodontal tissue destruction induced by systemic bacterial challenge in known susceptible (BALB/c) and resistant (C57BL/6) mouse lineages. MATERIAL AND METHODS: Animals, 6-8 weeks old, were allocated into three experimental groups: Negative control (C), Gavage with sterile carboxymethyl cellulose 2%-without bacteria (Sham), and Gavage with carboxymethyl cellulose 2% + Porphyromonas gingivalis (Pg-W83). Before infection, all animals received antibiotic treatment (sulfamethoxazole/trimethoprim, 400/80 mg/5 mL) for 7 days, followed by 3 days of rest. Microbial challenge was performed 3 times per week for 1, 2, or 3 weeks. After that, the animals were kept until the completion of 42 days of experiments, when they were euthanized. The alveolar bone microarchitecture was assessed by computed microtomography. RESULTS: Both C57BL/6 and BALB/c mice exhibited significant bone volume loss and lower trabecular thickness as well as greater bone porosity compared to the (C) and (Sham) groups after 1 week of microbial challenge (p < .001). When comparing only the gavage groups regarding disease implantation, time and lineage, it was possible to observe that within 1 week of induction the disease was more established in BALB/c than in C57BL/6 (p < .05). CONCLUSIONS: Our results reflected that after 1 week of microbial challenge, there was evidence of alveolar bone loss for both lineages, with the loss observed in BALB/c mice being more pronounced.

Acellular dermal matrix graft with or without enamel matrix derivative for root coverage in smokers: a randomized clinical study.

AIM: The aim of this randomized controlled clinical study was to compare the use of an acellular dermal matrix graft (ADMG) with or without the enamel matrix derivative (EMD) in smokers to evaluate which procedure would provide better root coverage. MATERIAL AND METHODS: Nineteen smokers with bilateral Miller Class I or II gingival recessions ≥3 mm were selected. The test group was treated with an association of ADMG and EMD, and the control group with ADMG alone. Probing depth, relative clinical attachment level, gingival recession height, gingival recession width, keratinized tissue width and keratinized tissue thickness were evaluated before the surgeries and after 6 months. Wilcoxon test was used for the statistical analysis at significance level of 5%. RESULTS: No significant differences were found between groups in all parameters at baseline. The mean gain recession height between baseline and 6 months and the complete root coverage favored the test group (p = 0.042, p = 0.019 respectively). CONCLUSION: Smoking may negatively affect the results achieved through periodontal plastic procedures; however, the association of ADMG and EMD is beneficial in the root coverage of gingival recessions in smokers, 6 months after the surgery.

A Randomized comparative clinical study of two surgical procedures to improve root coverage with the acellular dermal matrix graft.

AIM: This randomized, controlled, clinical study compared two surgical techniques for root coverage with the acellular dermal matrix graft (ADMG) to evaluate which procedure could provide better root coverage and greater amounts of keratinized tissue. MATERIALS AND METHODS: Fifteen pairs of bilateral Miller Class I or II gingival recessions were treated and assigned randomly to the test group, and the contra-lateral recessions were assigned to the control group. The ADMG was used in both groups. In the control group, the graft and flap were positioned at the level of the cemento-enamel junction (CEJ), and in the test group, the graft was positioned 1 mm apical to the CEJ and the flap 1 mm coronal to the CEJ. The clinical parameters were taken before the surgeries and after 6 months. The gingival recession area, a new parameter, was measured in standardized photographs through a special device and software. RESULTS: There were statistically significant differences favouring the proposed technique for all parameters except for the amount of keratinized tissue at 6 months. CONCLUSIONS: The proposed test technique is more suitable for root coverage procedures with ADMG, and the new parameter evaluated appears valuable for root coverage analysis. (Clinicaltrials.gov Identifier: NCT01175720).

Enamel matrix derivative and transforming growth factor-beta1 in Class III furcation defects. A histomorphometric study in dogs.

The objective of this study was to evaluate histomorphometrically, in dogs, the effect of enamel matrix derivative (EMD), with or without transforming growth factor-beta1 (TGF-beta1), in a periodontal Class III furcation model. Class III furcation defects were created in P3 and P4 of six dogs. The defects were allowed to stabilize for 21 days. Four experimental conditions were established: G1: control (propylene glycol alginate); G2: EMD; G3: TGF-beta1 and G4: EMD + TGF-beta1. After 12 weeks, the dogs were euthanized. Their jaws were removed, fixed, decalcified, dehydrated and embedded in paraffin. Semi-serial sections were obtained, stained and examined with light microscopy. The furcation defects were not completely closed in any specimen, with downgrowth of the junctional epithelium into the furcation area. The morphologic characteristics of the newly formed tissues in the test groups were similar to the control group, with slight differences in average values, but with no statistically significant differences between the groups. This study was not able to provide histological evidence that EMD, TGF-beta1 and EMD + TGF-beta1 present additional advantages in periodontal bone formation in a Class III furcation model in dogs.

Buccal bone plate remodeling after immediate implant placement with and without synthetic bone grafting and flapless surgery: radiographic study in dogs.

Recent studies in animals have shown pronounced resorption of the buccal bone plate after immediate implantation. The use of flapless surgical procedures prior to the installation of immediate implants, as well as the use of synthetic bone graft in the gaps represent viable alternatives to minimize buccal bone resorption and to favor osseointegration. The aim of this study was to evaluate the healing of the buccal bone plate following immediate implantation using the flapless approach, and to compare this process with sites in which a synthetic bone graft was or was not inserted into the gap between the implant and the buccal bone plate. Lower bicuspids from 8 dogs were bilaterally extracted without the use of flaps, and 4 implants were installed in the alveoli in each side of the mandible and were positioned 2.0 mm from the buccal bone plate (gap). Four groups were devised: 2.0-mm subcrestal implants (3.3 × 8 mm) using bone grafts (SCTG), 2.0-mm subcrestal implants without bone grafts (SCCG), equicrestal implants (3.3 × 10 mm) with bone grafts (ECTG), and equicrestal implants without bone grafts (ECCG). One week following the surgical procedures, metallic prostheses were installed, and within 12 weeks the dogs were sacrificed. The blocks containing the individual implants were turned sideways, and radiographic imaging was obtained to analyze the remodeling of the buccal bone plate. In the analysis of the resulting distance between the implant shoulder and the bone crest, statistically significant differences were found in the SCTG when compared to the ECTG (P = .02) and ECCG (P = .03). For mean value comparison of the resulting linear distance between the implant surface and the buccal plate, no statistically significant difference was found among all groups (P > .05). The same result was observed in the parameter for presence or absence of tissue formation between the implant surface and buccal plate. Equicrestally placed implants, in this methodology, presented little or no loss of the buccal bone. The subcrestally positioned implants presented loss of buccal bone, even though synthetic bone graft was used. The buccal bone, however, was always coronal to the implant shoulder.

The effect of a single episode of antimicrobial photodynamic therapy in the treatment of experimental periodontitis. Microbiological profile and cytokine pattern in the dog mandible.

The purpose of this study was to evaluate the effect of a single application of antimicrobial photodynamic therapy (aPDT) on microbiological profile and cytokine pattern in dogs. Periodontal disease was induced by placing 3.0 silk ligatures around the mandibular pre-molars bilaterally during 8 weeks. The dogs were randomly treated with aPDT using a dye/laser system, scaling and root planning (SRP), or with the association of treatments (SRP + aPDT). Plaque samples were collected at baseline, 1, 3, and 4 weeks, and the mean counts of 40 species were determined using DNA-DNA hybridization. Gingival biopsies were removed and the expression of tumor necrosis factor alpha (TNF-α), receptor activator of NF-kB ligand (RANKL), osteoprotegerin (OPG), matrix metalloproteinase (MMP-1), interleukin (IL) 6, IL-10 and total bacterial load by analysis of 16 S rRNA gene were evaluated through real-time PCR. The results shows that the levels of the majority of the species were reduced 1 week post-therapy for all treatments, however, an increase in counts of Prevotella intermedia (p = 0.00), Prevotella. nigrescens (p = 0.00) and Tannerella forsythia (p = 0.00) was observed for aPDT and SRP + aPDT. After 4 weeks, a regrowth of Porphyromonas gingivalis (p = 0.00) and Treponema denticola (p = 0.00), was observed for all treatments. Also, a strikingly reduction of counts on counts of Aggregatibacter actinomycetemcomitans was observed for the aPDT (p = 0.00). For the cytokine pattern, the results were similar for all treatments, and a reduction in the expression of cytokines and bacterial load was observed throughout the study. Our results suggest that SRP, aPDT in a single application, and SRP + aPDT affects different bacterial species and have similar effects on the expression of cytokines evaluated during the treatment of ligature-induced periodontitis.

Decitabine Inhibits Bone Resorption in Periodontitis by Upregulating Anti-Inflammatory Cytokines and Suppressing Osteoclastogenesis.

DNA methylation controls several inflammatory genes affecting bone homeostasis. Hitherto, inhibition of DNA methylation in vivo in the context of periodontitis and osteoclastogenesis has not been attempted. Ligature-induced periodontitis in C57BL/6J mice was induced by placing ligature for five days with Decitabine (5-aza-2'-deoxycytidine) (1 mg/kg/day) or vehicle treatment. We evaluated bone resorption, osteoclast differentiation by tartrate-resistant acid phosphatase (TRAP) and mRNA expression of anti-inflammatory molecules using cluster differentiation 14 positive (CD14+) monocytes from human peripheral blood. Our data showed that decitabine inhibited bone loss and osteoclast differentiation experimental periodontitis, and suppressed osteoclast CD14+ human monocytes; and conversely, that it increased bone mineralization in osteoblastic cell line MC3T3-E1 in a concentration-dependent manner. In addition to increasing IL10 (interleukin-10), TGFB (transforming growth factor beta-1) in CD14+ monocytes, decitabine upregulated KLF2 (Krüppel-like factor-2) expression. Overexpression of KLF2 protein enhanced the transcription of IL10 and TGFB. On the contrary, site-directed mutagenesis of KLF2 binding site in IL10 and TFGB abrogated luciferase activity in HEK293T cells. Decitabine reduces bone loss in a mouse model of periodontitis by inhibiting osteoclastogenesis through the upregulation of anti-inflammatory cytokines via KLF2 dependent mechanisms. DNA methyltransferase inhibitors merit further investigation as a possible novel therapy for periodontitis.

Aptamers recognizing fibronectin confer improved bioactivity to biomaterials and promote new bone formation in a periodontal defect in rats.

The use of alloplastic materials in periodontal regenerative therapies is limited by their incapacity to establish a dynamic dialog with the surrounding milieu. The aim of the present study was to control biomaterial surface bioactivity by introducing aptamers to induce the selective adsorption of fibronectin from blood, thus promoting platelets activation in vitro and bone regeneration in vivo. A hyaluronic acid/polyethyleneglycole-based hydrogel was enriched with aptamers selected for recognizing and binding fibronectin. In vitro, the capacity of constructs to support osteoblast adhesion, as well as platelets aggregation and activation was assessed by chemiluminescence within 24 h. Matrices were then evaluated in a rat periodontal defect to assess their regenerative potential by microcomputed tomography (µCT) and their osteogenic capacity by Luminex assay 5, 15 and 30 d postoperatively. Aptamers were found to confer matrices the capacity of sustaining firm cell adhesion (p = 0.0377) and to promote platelets activation (p = 0.0442). In vivo, aptamers promoted new bone formation 30 d post-operatively (p < 0.001) by enhancing osteoblastic lineage commitment maturation. Aptamers are a viable surface modification, which confers alloplastic materials the potential capacity to orchestrate blood clot formation, thus controlling bone healing.

Potential of bioactive glass particles of different size ranges to affect bone formation in interproximal periodontal defects in dogs.

BACKGROUND: The aim of this study was to compare the potential of bioactive glass particles of different size ranges to affect bone formation in periodontal defects, using the guided tissue regeneration model in dogs. METHODS: In six dogs, 2-wall intrabony periodontal defects were surgically created and chronified on the mesial surfaces of mandibular third premolars and first molars bilaterally. After 1 month, each defect was randomly assigned to treatment with bioabsorbable membrane in association with bioactive glass with particle sizes between 300 and 355 microm (group 1) or between 90 and 710 microm (group 2), membrane alone (group 3), or negative control (group 4). The dogs were sacrificed 12 weeks after surgeries, and histomorphometric measurements were made of the areas of newly formed bone, new mineralized bone, and bioactive glass particle remnants. RESULTS: With regard to the area of bioactive glass particle remnants, there was a statistically significant difference between groups 1 and 2, favoring group 1. There were greater areas of mineralized bone in groups 1 and 2 compared to groups 3 and 4 (P <0.05). CONCLUSION: The bioactive glass particles of small size range underwent faster resorption and substitution by new bone than the larger particles, and the use of bioactive glass particles favored the formation of mineralized bone.

The impact of predatory bacteria on experimental periodontitis.

BACKGROUND: This study evaluated the effects of topical administration of Bdellovibrio bacteriovorus HD100 on experimental periodontitis (EP) in rats. METHODS: Thirty-two rats were divided into groups C (control), EP, C-HD100, and EP-HD100. At day 0, animals of groups EP and EP-HD100 received cotton ligatures around mandibular first molars (MFM). In groups C-HD100 and EP-HD100, 1 mL of suspensions containing B. bacteriovorus HD100 was topically administered in the subgingival region of MFMs at days 0, 3, and 7. Animals were euthanized at day 14. Gingival tissue, hemimandibles, and oral biofilm were collected. Data were statistically analyzed. RESULTS: Group EP-HD100 presented greater bone volume and lower connective tissue attachment loss (CTAL) than group EP (P < 0.05). Group EP-HD100 presented greater proportions of Actinomyces and Streptococcus-like species and lower proportions of Prevotella intermedia, Peptostreptococcus micros, Fusobacterium nucleatum, Fusobacterium polymorphum, Eikenella corrodens, Eubacterium nodatum, Campylobacter gracilis, Capnocytophaga sputigena, and Veillonella parvula-like species than group EP. Group EP-HD100 presented greater levels of osteoprotegerin and gene expression of interleukin (IL)-17, IL-10, and forkhead box P3 than group EP (P < 0.05). CONCLUSION: Topical use of B. bacteriovorus HD100 promotes a protective effect against alveolar bone loss and CTAL in rats with EP.