Efficacy and safety of P11-4 for the treatment of periodontal defects in dogs.

OBJECTIVES: This study's aim was to investigate the safety and performance of a self-assembling peptide matrix (SAPM) P11-4 for the treatment of periodontal disease in a controlled pre-clinical study. MATERIALS AND METHODS: Acute buccal bony dehiscence defects (LxW: 5 × 3 mm) were surgically created on the distal root of four teeth on one mandible side of 7 beagle dogs followed by another identical surgery 8 weeks later on the contralateral side. SAPM P11-4 (with and without root conditioning with 24% EDTA (T1, T2)), Emdogain® (C) and a sham intervention (S) were randomly applied on the four defects at each time point. Four weeks after the second surgery and treatment, the animals were sacrificed, the mandibles measured by micro-computed tomography (µ-CT) and sections of the tissue were stained and evaluated histologically. RESULTS: Clinically and histologically, no safety concerns or pathological issues due to the treatments were observed in any of the study groups at any time point. All groups showed overall similar results after 4 and 12 weeks of healing regarding new cementum, functionality of newly formed periodontal ligament and recovery of height and volume of the new alveolar bone and mineral density. CONCLUSION: A controlled clinical study in humans should be performed in a next step as no adverse effects or safety issues, which might affect clinical usage of the product, were observed. CLINICAL RELEVANCE: The synthetic SAPM P11-4 may offer an alternative to the animal-derived product Emdogain® in the future.

Long-term clinical and radiographic results after treatment or no treatment of small buccal bone dehiscences at posterior dental implants: A randomized, controlled clinical trial.

AIM: To test whether or not buccal vertical bone dehiscences (≤5 mm) around posterior implants left for spontaneous healing (SH) result in the same clinical and radiologic outcome as dehiscences treated with guided bone regeneration (GBR) at 7.5 years after implant placement (IMPL). MATERIALS AND METHODS: Twenty-two patients receiving 28 posterior implants with a small non-contained buccal bone dehiscence (≤5 mm) were randomly assigned to the SH or the GBR group. Implants were loaded at 6 months. Clinical parameters (probing depths, sulcus bleeding index, plaque index) and approximal marginal radiographic bone levels were assessed regularly up to at least 6.8 years. The vertical extension of the dehiscences was measured clinically at IMPL and abutment connection and radiographically on cone beam computed tomographys at a mean follow-up time of 7.5 years. RESULTS: Twenty patients with a total of 26 implants were recalled at 7.5 years (9.1% dropout). The implant/crown survival rates were 100% in both groups. Stable peri-implant tissues were observed in both groups showing only minimal signs of inflammation. During the entire study period (IMPL-7.5-year follow-up), the median buccal vertical bone gain measured 1.61 mm for the GBR group and 0.62 for the SH group showing no significant difference between the groups. Also, at 7.5 years, the median approximal marginal bone levels (GBR: 0.53; SH: 0.68) were not significantly different between the two groups (p = .61) while the remaining median buccal vertical dehiscences were larger in the SH group (2.51 mm) compared to the GBR group (1.66 mm; p = .02). CONCLUSIONS: Implants with small non-contained buccal bone dehiscences exhibited high implant survival rates and healthy peri-implant tissues at 7.5 years. In the GBR group, the buccal vertical bone levels were higher compared to the SH group but remained stable over the entire study period for both treatments.

Soft tissue substitutes to increase gingival thickness: Histologic and volumetric analyses in dogs.

OBJECTIVES: To evaluate the histologic and volumetric changes of gingival tissues following grafting with collagen-based matrices at labial aspect of teeth in canines. MATERIALS AND METHODS: Gingival augmentation was performed in the mandibular incisor area using two types of xenogeneic cross-linked collagen matrices (CCMs), bovine CCM for BCCM group and porcine CCM for PCCM group, whereas the contralateral sides remained untreated (B-control group and P-control group). Descriptive histology, histometric and volumetric analyses were performed after 12 weeks. For statistical comparison between each test group and respective control group, paired t test was used for histometric analysis, and repeated-measured analysis of variance was used for volumetric analysis (p < 0.05). RESULTS: An increased number of rete pegs and an enhanced formation of new blood vessels were observed at both grafted sites compared to the corresponding control sites. There was statistically significant gain of horizontal thickness only in BCCM group (1.36 ± 0.27 mm vs. 1.26 ± 0.34 mm; p < 0.05) compared to the B-control groups. CONCLUSION: BCCM was effective for gingival augmentation in terms of horizontal thickness at the labial aspect of teeth at 12 weeks post-surgery.

Clinical and patient-reported outcomes of implants placed in autogenous bone grafts and implants placed in native bone: A case-control study with a follow-up of 5-16 years.

AIMS: To compare the radiographic marginal bone levels of implants placed in sites previously augmented with autogenous bone grafts and implants placed in native bone. Secondary outcomes included: implant survival, periodontal/peri-implant parameters as well as short- and long-term patient-reported outcome measures. MATERIALS AND METHODS: The study was designed as a case-control study including 38 patients equally distributed into two groups (previously augmented with autogenous bone blocks [AB] and implants placed in native bone [NB]). In total, 67 implants were placed. Clinical, radiographic and patient-reported outcome measures (PROMs), and complication rates were assessed based on a chart review and at a follow-up examination (≧5 years after implant placement). Nonparametric mixed models were applied for the comparison of the two groups because of the clustered data. The data were analyzed descriptively, and p-values were calculated using nonparametric mixed models to account for the clustered data. RESULTS: The mean follow-up time was 10.2 years (range 6-13 years; AB) and 8.3 years (range 5-16 years; NB). One implant was lost in group NB (97.5% survival rate) and none in group AB (100%). Following primary augmentation, six major complications (wound dehiscences, acute pulpitis, intra- and extraoral sensitivity disturbances) were observed at the donor sites. At time of implant placement, only minimal complications occurred and only in group NB. Median marginal bone levels at the follow-up were significantly higher in group NB (1.15; Q1: 0.50 mm/Q3: 1.83 mm) than in group AB (1.58; Q1: 1.01 mm/Q3: 2.40 mm; p = 0.0411). Probing depth, bleeding on probing and recession values were similar in both groups. PROMs revealed high visual analog scale values (i.e., high satisfaction) for both procedures. CONCLUSIONS: Dental implants placed in sites augmented with autogenous bone or in native bone revealed healthy peri-implant tissues after 5-16 years. Marginal bone levels were significantly higher for implant placed in native bone. Complications following primary augmentation encompassed every third patient but were mostly transient.

Porphyromonas gingivalis Outer Membrane Vesicles Induce Selective Tumor Necrosis Factor Tolerance in a Toll-Like Receptor 4- and mTOR-Dependent Manner.

Porphyromonas gingivalis is an important member of the anaerobic oral flora. Its presence fosters growth of periodontal biofilm and development of periodontitis. In this study, we demonstrated that lipophilic outer membrane vesicles (OMV) shed from P. gingivalis promote monocyte unresponsiveness to live P. gingivalis but retain reactivity to stimulation with bacterial DNA isolated from P. gingivalis or AIM2 ligand poly(dA·dT). OMV-mediated tolerance of P. gingivalis is characterized by selective abrogation of tumor necrosis factor (TNF). Neutralization of interleukin-10 (IL-10) during OMV challenge partially restores monocyte responsiveness toP. gingivalis; full reactivity toP. gingivalis can be restored by inhibition of mTOR signaling, which we previously identified as the major signaling pathway promoting Toll-like receptor 2 and Toll-like receptor 4 (TLR2/4)-mediated tolerance in monocytes. However, despite previous reports emphasizing a central role of TLR2 in innate immune recognition of P. gingivalis, our current findings highlight a selective role of TLR4 in the promotion of OMV-mediated TNF tolerance: only blockade of TLR4-and not of TLR2-restores responsiveness toP. gingivalis Of further note, OMV-mediated tolerance is preserved in the presence of cytochalasin B and chloroquine, indicating that triggering of surface TLR4 is sufficient for this effect. Taking the results together, we propose that P. gingivalis OMV contribute to local immune evasion of P. gingivalis by hampering the host response.

Neutrophil extracellular trap formation in supragingival biofilms.

BACKGROUND: Oral biofilms are the causative agents of the highly prevalent oral diseases periodontitis and caries. Additionally, the host immune response is thought to play a critical role in disease onset. Neutrophils are known to be a key host response factor to bacterial challenge on host surfaces. Release of neutrophil extracellular traps (NETs) as a novel antimicrobial defense strategy has gained increasing attention in the past years. Here, we investigated the influx of neutrophils into the dental plaque and the ability of oral bacteria to trigger intra-biofilm release of NETs and intracellular proteins. METHODS: Supragingival biofilms and whole saliva were sampled from systemically healthy subjects participating in an experimental gingivitis study. Biofilms were analysed by immunofluorescence followed by confocal and fluorescence microscopy. Moreover, concentrations of cytokines and immune-associated proteins in biofilm suspensions and saliva were assessed by ELISA. Neutrophils obtained from blood were stimulated with twelve bacterial species isolated from cultured biofilms or with lipopolysaccharide to monitor NET formation. RESULTS: Neutrophils, NETs, neutrophil-associated proteins (myeloperoxidase, elastase-2, cathepsin G, cathelicidin LL-37), interleukin-8, interleukin-1ß and tumor necrosis factor were detected within plaque samples and saliva. All tested bacterial species as well as the polymicrobial samples isolated from the plaque of each donor induced release of NETs and interleukin-8. The degree of NET formation varied among different subjects and did not correlate with plaque scores or clinical signs of local inflammation. CONCLUSIONS: Our findings indicate that neutrophils are attracted towards dental biofilms, in which they become incorporated and where they are stimulated by microbes to release NETs and immunostimulatory proteins. Thus, neutrophils and NETs may be involved in host biofilm control, although their specific role needs to be further elucidated. Moreover, inter-patient variability suggests NET formation as a potential factor influencing the individual course of disease.

Perceptibility and Acceptability of Color Differences of Single-Tooth Implants at the Restoration and Mucosa Levels: An Exploratory Clinical Study.

PURPOSE: The aim of the present study was to assess the perceptibility and acceptability threshold values for color differentiation at the restoration and mucosa levels. MATERIALS AND METHODS: One restored single-tooth implant and the contralateral reference tooth were spectrophotometrically assessed in 20 patients. Perceptibility and acceptability were evaluated by dentists, dental technicians, and laypeople. RESULTS: Dental technicians had the highest sensitivity in the perception of tooth color differences (ΔE = 2.7), followed by dentists (ΔE = 3.3) and laypeople (ΔE = 4.4). Acceptability threshold values were generally higher than perceptibility threshold in all groups. Dental technicians exhibited the highest sensitivity in the perception of mucosa color differences (50% perceptibility at ΔE = 2.65), followed by dentists (ΔE > 3.7) and laypeople (ΔE > 6). CONCLUSION: Color differences were tolerated with varying degrees among the three groups. Laypeople accepted higher color differences at the mucosa level.

MicroRNA profiling of clear cell renal cell cancer identifies a robust signature to define renal malignancy.

MicroRNAs are short single-stranded RNAs that are associated with gene regulation at the transcriptional and translational level. Changes in their expression were found in a variety of human cancers. Only few data are available on microRNAs in clear cell renal cell carcinoma (ccRCC). We performed genome-wide expression profiling of microRNAs using microarray analysis and quantification of specific microRNAs by TaqMan real-time RT-PCR. Matched malignant and non-malignant tissue samples from two independent sets of 12 and 72 ccRCC were profiled. The microarray-based experiments identified 13 over-expressed and 20 down-regulated microRNAs in malignant samples. Expression in ccRCC tissue samples compared with matched non-malignant samples measured by RT-PCR was increased on average by 2.7- to 23-fold for the hsa-miR-16, -452*, -224, -155 and -210, but decreased by 4.8- to 138-fold for hsa-miR-200b, -363, -429, -200c, -514 and -141. No significant associations between these differentially expressed microRNAs and the clinico-pathological factors tumour stage, tumour grade and survival rate were found. Nevertheless, malignant and non-malignant tissue could clearly be differentiated by their microRNA profile. A combination of miR-141 and miR-155 resulted in a 97% overall correct classification of samples. The presented differential microRNA pattern provides a solid basis for further validation, including functional studies.

Influence of wound closure on volume stability with the application of different GBR materials: an in vitro cone-beam computed tomographic study.

PURPOSE: To assess the influence of using different combinations of guided bone regeneration (GBR) materials on volume changes after wound closure at peri-implant dehiscence defects. METHODS: In 5 pig mandibles, standardized bone defects were created and implants were centrally placed. The defects were augmented using different combinations of GBR materials: xenogeneic granulate and collagen membrane (group 1, n=10), xenogeneic granulate and alloplastic membrane (group 2, n=10), alloplastic granulates and alloplastic membrane (group 3, n=10). The horizontal thickness was assessed using cone-beam computed tomography before and after suturing. Measurements were performed at the implant shoulder (HT0) and at 1 mm (HT1) and 2 mm (HT2) below. The data were statistically analysed using the Wilcoxon signed-rank test to evaluate within-group differences. Bonferroni correction was applied when calculating statistical significance between the groups. RESULTS: The mean horizontal thickness before suturing was 2.55±0.53 mm (group 1), 1.94±0.56 mm (group 2), and 2.49±0.73 mm (group 3). Post-suturing, the values were 1.47±0.31 mm (group 1), 1.77±0.27 mm (group 2), and 2.00±0.48 mm (group 3). All groups demonstrated a loss of horizontal dimension. Intragroup changes exhibited significant differences in group 1 (P<0.001) and group 3 (P<0.01). Intergroup comparisons revealed statistically significant differences of the relative changes between groups 1 and 2 (P=0.033) and groups 1 and 3 (P=0.015). CONCLUSIONS: Volume change after wound closure was minimized by using an alloplastic membrane. The stability of the augmented horizontal thickness was most ensured by using this type of membrane irrespective of the bone substitute material used for membrane support.