Elucidating the molecular healing of intrabony defects following non-surgical periodontal therapy: A pilot study.

OBJECTIVE: To elucidate the molecular healing of intrabony defects following non-surgical periodontal therapy (NSPT) using gingival crevicular fluid (GCF). BACKGROUND DATA: Currently limited information is available regarding the GCF of intrabony defects and the change in biomarker levels in the GCF at early time points following treatment interventions. METHODS: Twenty-one patients (Periodontitis Stage III or IV) who have received NSPT, contributing one intrabony defect and one healthy site were included in this study. GCF sampling was performed at baseline, 1 day, 5 days and 3 months after NSPT. Multiplex bead immunoassays allowed the profiling of GCF for 27 markers, associated with inflammation and repair/regeneration. A mixed effects model with Bonferroni correction for multiple comparisons was employed to compare the changes in the levels of GCF markers over time. RESULTS: Following NSPT, changes were observed for several GCF markers, marked by significant increases 1 day post-intervention, before returning to baseline levels by 3 months. Specifically, GCF concentrations of IL-2, IL-4, IL-6, IL-8, MMP-1, MMP-3, TIMP-1 and FGFb significantly increased 1 day after NSPT. Signs of activation of cellular senescence were observed 1 day following treatment of intrabony defects, rapidly regressing by 5 days. CONCLUSION: Significant molecular changes are observed as early as 1 day following NSPT in intrabony defects, along with activation of cellular senescence.

Local drug delivery in the treatment of furcation defects in periodontitis: a systematic review.

OBJECTIVES: To evaluate the effect of subgingival administration of various antimicrobials and host-modulating agents in furcation defects as an adjunct to scaling and root planing (SRP) compared to SRP alone or combined with placebo. METHODS: A systematic review was carried out using MEDLINE-PubMed, Embase, and Scopus for articles up to October 2022 in addition to hand searches. All longitudinal studies that evaluated the effect of subgingival application of antimicrobial and host-modulating agents in furcation defects as adjuncts to SRP compared to SRP alone or SRP + placebo with at least 3 months of follow-up were eligible for inclusion. RESULTS: A total of eight studies were included. Superior clinical treatment outcomes were shown when alendronate, rosuvastatin, boric acid, simvastatin, and tetracycline (only at 3 months) were utilized in furcation defects in conjunction with SRP alone or SRP + placebo. Significant improvement was reported in radiographic bone defect depth and defect depth reduction when SRP was supplemented with alendronate, rosuvastatin, boric acid, and simvastatin. CONCLUSIONS: Within the limitations of this review, the adjunctive subgingival administration of medications and host-modulating agents in furcation defects may confer additional clinical and radiographic benefits than non-surgical periodontal treatment alone. Future investigations are needed to confirm their long-term effectiveness. CLINICAL RELEVANCE: Local host modulators and antimicrobials may be used supplementary to enhance the clinical and radiographic treatment outcomes of conventional periodontal therapy in furcation defects.

Expression of Wnt signaling agonists and antagonists in periodontitis and healthy subjects, before and after non-surgical periodontal treatment: A systematic review.

Periodontitis is a preventable and treatable multifactorial chronic inflammatory disease that can lead to irreversible periodontal destruction and tooth loss. Wnt signaling and its regulators play an important role in periodontal inflammation, destruction, regeneration, and reconstruction. This systematic review aimed at investigating the involvement of Wnt signaling agonists and antagonists in periodontitis and healthy subjects, before and after periodontal treatment. Electronic searches were carried out using MEDLINE/PubMed, EMBASE, and Cochrane Library databases in addition to hand searches. Studies having different designs assessing the levels of Wnt signaling antagonist and agonist levels in gingival crevicular fluid, serum, and tissue in patients diagnosed with periodontitis or gingivitis, compared with healthy individuals were included. In addition, studies compared these levels in periodontitis patients before and after non-surgical periodontal therapy were also eligible. Sixteen studies met the eligibility criteria. Sclerostin (SOST) has been mainly investigated in the literature (8 publications). Sclerostin (5 studies), Wnt-5a (2 studies), secreted frizzled-related protein 1 (SFRP1) (3 studies), and ß-catenin (3 studies) show increased levels in periodontitis compared with periodontal health. Strong correlations between marker levels and periodontal clinical parameters were identified for SOST (5 studies), SFRP1 (2 studies), and ß-catenin (2 studies). SOST (3 studies) and SFRP1 (1 study) levels significantly decrease following non-surgical periodontal treatment. The present systematic review demonstrated an association between Wnt signaling agonist and antagonist levels and periodontitis. Wnt agonists and antagonists may serve as valuable diagnostic and prognostic markers for periodontitis onset and progression. Further case-control and longitudinal studies should be conducted for different Wnt signaling agonists and antagonists.

Postextraction ridge preservation by using dense PTFE membranes: A systematic review and meta-analysis.

STATEMENT OF PROBLEM: The use of dense polytetrafluoroethylene (dPTFE) membranes in alveolar ridge preservation may help reduce the risk of bacterial contamination and infection, maintaining the soft-tissue anatomy. However, systematic reviews on their efficacy in postextraction sites are lacking. PURPOSE: The purpose of this systematic review and meta-analysis was to assess the efficacy of alveolar ridge preservation with dPTFE membranes when used alone or in combination with bone grafting materials in postextraction sites. MATERIAL AND METHODS: An electronic search up to February 2021 was conducted by using PubMed, Embase, and the Cochrane library to detect studies using dPTFE membranes in postextraction sites. An additional manual search was performed in relevant journals. Clinical and radiographic dimensional changes of the alveolar ridge, histomorphometric, microcomputed tomography, implant-related findings, and rate of complications were recorded. One-dimensional meta-analysis was performed to calculate the overall means and 95% confidence intervals (α=.05). RESULTS: A total of 23 studies, 14 randomized controlled trials, 4 retrospective cohort studies, 3 case series, and 2 prospective nonrandomized clinical trials, met the inclusion criteria. Five studies were included in the quantitative analysis. The meta-analysis revealed that the use of dPTFE membranes resulted in a statistically significant (P=.042) increase in clinical keratinized tissue of 3.49 mm (95% confidence interval [CI]: 0.16, 6.83) when compared with extraction alone. Metaregression showed that the difference of 1.10 mm (95% CI: -0.14, 2.35) in the radiographic horizontal measurements was not significant (P=.082), but the difference of 1.06 mm (95% CI: 0.51, 1.62) in the radiographic vertical dimensional change between dPTFE membranes+allograft and extraction alone was statistically significant (P<.001). CONCLUSIONS: The use of dPTFE membranes was better than extraction alone in terms of keratinized tissue width and radiographic vertical bone loss.

Molecular profiling of intrabony defects' gingival crevicular fluid.

AIM: To profile, for the first time, the gingival crevicular fluid (GCF) of intrabony defects against a wide array of inflammatory and regenerative markers. MATERIALS AND METHODS: Twenty-one patients contributed one intrabony defect and one periodontally healthy site. Clinical and radiographic measures were obtained. GCF samples were analyzed with multiplex bead immunoassays over 27 markers previously identified by our group. Comparisons were performed using Wilcoxon matched-pairs signed-ranks tests, using a Bonferroni corrected α = 0.05/27 = 0.0019. RESULTS: Intrabony defect sites presented significantly increased GCF volume and disease-associated clinical and radiographic characteristics (p < .05). Intrabony defect sites presented significantly increased IL-1α, IL-1ß, IL-6, IFN-γ, and MMP-8 levels compared with periodontally healthy sites (p < .0019). For regeneration markers, significantly higher FGF basic and VEGF levels were observed (p < .0019). Notably, traits of cell senescence were identified for the first time in the GCF. CONCLUSIONS: The differentiation of intrabony defects from periodontally healthy control sites can be based on clinical and radiographic measures and on a differentiated GCF profile that is site-specific. Alongside catabolic processes, through significant up-regulation of inflammation and connective tissue remodeling, unique molecular characteristics of intrabony defects may render them a microenvironment amenable to regeneration. Traits of the senescence-associated secretory phenotype may suggest the existence of senescent cells during periodontal inflammation in intrabony defects.

Expression of inflammatory biomarkers and growth factors in gingival crevicular fluid at different healing intervals following non-surgical periodontal treatment: A systematic review.

BACKGROUND: Non-surgical periodontal treatment (NSPT) is widely employed for the treatment of periodontal disease and yields significant clinical improvements. Gingival crevicular fluid (GCF) can be used to profile health and disease, and recent technological advances, such as multiplex bead immunoassays, are promising in identifying a wider array of GCF factors with the ultimate aim to predict the treatment response. OBJECTIVE: The aim of this systematic review was to compare the expression of GCF markers using multiplex bead immunoassays before treatment and during early, average, or late healing period, following non-surgical periodontal treatment (NSPT). METHODS: An electronic literature search was conducted by two independent examiners (VK and NC) in MEDLINE, EMBASE, OpenGrey, LILACS, and Cochrane Library up to January 2020. The PICO question formulated was as follows: "In patients with periodontal disease, does the expression of gingival crevicular fluid (GCF) markers detected using multiplex bead immunoassay differ at baseline compared with early (≤30 days), average (6-8 weeks), or late (≥3 months) healing after intervention?" RESULTS: A total of 366 publications were obtained and reviewed for eligibility for inclusion. Of these, 12 publications fulfilled the inclusion criteria and were included in the present review. Data for a total of 31 different GCF markers were extracted and summarized for early, average, or late healing after NSPT. Early healing following NSPT (≤ 30 days) indicated an increase in IL-1ß, TNFα, and IL-10. At the average healing period (6-8 weeks), IL-1ß, IL-1α, IL-6, TNF-α, IFN-γ, GM-CSF, MCP-1, and MIP-1α were all reduced, compared to their respective baseline values. Three months after NSPT, IL-1ß, IL-4, IL-6, IL-10, TNF-α, and IFN-γ were detected at reduced levels, compared to pre-treatment levels. Overall, the changes following treatment indicated a reduction of inflammation present at baseline. CONCLUSION: Following non-surgical periodontal treatment, an upregulation of inflammation markers is noted early post-operatively and a subsequent reduction of their levels three months following treatment. The investigation of levels of GCF markers associated with inflammation and regeneration, especially using multiplex bead immunoassay technologies, is a valuable tool to better understand the processes associated with healing following periodontal treatment.

Regenerative surgery versus access flap for the treatment of intra-bony periodontal defects: A systematic review and meta-analysis.

BACKGROUND: The aim of this systematic review was to compare clinical, radiographic and patient-reported outcomes (PROMs) in intra-bony defects treated with regenerative surgery or access flap. MATERIALS AND METHODS: A systematic review protocol was written following the PRISMA checklist. Electronic and hand searches were performed to identify randomized clinical trials (RCTs) on regenerative treatment of deep intra-bony defects (≥3 mm) with a follow-up of at least 12 months. Primary outcome variables were probing pocket depth (PPD) reduction, clinical attachment level (CAL) gain and tooth loss. Secondary outcome variables were Rec, radiographic bone gain, pocket "closure," PROMs and adverse events. Meta-analysis was carried out when possible. To evaluate treatment effect, odds ratios were combined for dichotomous data and mean differences for continuous data using a random-effect model. RESULTS: A total of 79 RCTs (88 articles) published from 1990 to 2019 and accounting for 3,042 patients and 3,612 intra-bony defects were included in this systematic review. Only 10 of included studies were rated at low risk of bias. A total of 13 meta-analyses were performed. All regenerative procedures provided adjunctive benefit in terms of CAL gain (1.34 mm; 0.95-1.73) compared with open flap debridement alone. Both enamel matrix derivative (EMD) and guided tissue regeneration (GTR) were superior to OFD alone in improving CAL (1.27 mm; 0.79-1.74 mm and 1.43 mm; 0.76-2.22, respectively), although with moderate-high heterogeneity. Among biomaterials, the addition of deproteinized bovine bone mineral (DBBM) improved the clinical outcomes of both GTR with resorbable barriers and EMD. Papillary preservation flaps enhanced the clinical outcomes. The strength of evidence was low to moderate. CONCLUSION: EMD or GTR in combination with papillary preservation flaps should be considered the treatment of choice for residual pockets with deep (≥3 mm) intra-bony defects.

Empirical or microbiologically guided systemic antimicrobials as adjuncts to non-surgical periodontal therapy? A systematic review.

BACKGROUND: It is unclear whether patients with specific subgingival microbiological profiles benefit more from adjunctive systemic antibiotics. AIMS: To answer the question: "What is the clinical benefit in periodontitis patients taking adjunctive systemic antimicrobials to non-surgical therapy, depending on pre-treatment detection of periodontopathogenic bacteria?" MATERIALS AND METHODS: A search was conducted in four electronic databases for randomized controlled trials reporting clinical outcomes following adjunctive antibiotic therapy for patients divided by baseline microbiological profiles. RESULTS: The initial search resulted in 643 papers, reduced to five after screening and author contact. Four of these studies were suitable for a fixed effects two-stage individual participant data meta-analysis adjusted for baseline data. Collectively, adjunctive amoxicillin and metronidazole yielded superior clinical results (measured as reduction of PPDs) compared to placebo. No significant differences were detected for the effect of adjunctive antibiotics by the detection of Aggregatibacter actinomycetemcomitans on PPDs ≥ 5 mm (WMD = 1.16, 95% CI [-5.37, 7.68], I2  = 37.8%) or other clinical outcomes. All included studies had low risk of bias. CONCLUSION: There is no evidence to suggest that baseline detection of periodontopathogenic bacteria should be used as criterion for prescribing adjunctive antibiotics, although only limited information on microbial data and specific antimicrobials was available for analysis.

Peptide coatings enhance keratinocyte attachment towards improving the peri-implant mucosal seal.

There is a critical need for preventing peri-implantitis as its prevalence has increased and dental implants lack features to prevent it. Research strategies to prevent peri-implantitis have focused on modifying dental implants to incorporate different antimicrobial agents. An alternative strategy consists of barring the expansion of the biofilm subgingivally by forming a long-lasting permucosal seal between the soft tissue and the implant surface. Here, we innovatively biofunctionalized titanium with bioinspired peptide coatings to strengthen biological interactions between epithelial cells and the titanium surface. We selected laminin 332- and ameloblastin-derived peptides (Lam, Ambn). Laminin 332 participates in the formation of hemidesmosomes by keratinocytes and promotes epithelial attachment around teeth; and ameloblastin, an enamel derived protein, is involved in tissue regeneration events following disruption of the periodontium. Lam, Ambn or combinations of both peptides were covalently immobilized on titanium discs. Successful immobilization of the peptides was confirmed by contact angle goniometry, X-ray photoelectron spectroscopy and fluorescent labelling of the peptides. Additionally, we confirmed the mechanical and thermochemical stability of the peptides on Ti substrates. Proliferation and hemidesmosome formation of human keratinocytes (TERT-2/OKF-6) were assessed by immunofluorescence labelling. The peptide-coated surfaces increased cell proliferation for up to 48 h in culture compared to control surfaces. Most importantly, formation of hemidesmosomes by keratinocytes was significantly increased on surfaces coated with Ambn + Lam peptides compared to control (p < 0.01) and monopeptide coatings (p < 0.005). Together, these results support the Ambn + Lam multipeptide coating as a promising candidate for inducing a permucosal seal around dental implants.

Implant and root canal treatment: Survival rates and factors associated with treatment outcome.

OBJECTIVES: To assess and compare the survival rates of implant and root canal treatment as well as to investigate the effect of patient and tooth related variables on the treatment outcome in a large-scale population-based study. METHODS: Dental records of patients who received root canal treatment and implant therapy were retrieved from the electronic records of the University of Minnesota School of Dentistry. Demographic characteristics, dental insurance status, socioeconomic status as well as medical history and tobacco use were recorded. The treatment outcome was included as a binary variable (survival/failure). RESULTS: A total of 13,434 records of patients who had implant (33.6%) or root canal therapy (66.4%) were included. The survival rate analysis and Kaplan-Meier table revealed the majority of the implants were removed within the first year (58.8%), while only 35.2% of the root canal treatments failed in the same time period. The overall survival rate was significantly (p < 0.001) higher for implant therapy (98.3%) compared to root canal treatment (72.7%). A statistically significant association was found between treatment (p 

Quantification of facial and smile esthetics.

STATEMENT OF PROBLEM: Whether deviations in alignment discrepancy, width-to-length ratio, application of the golden proportion, or number of teeth revealed in smile affect attractiveness is yet unknown. PURPOSE: The purpose of this analytical study was to quantify dental and facial esthetics to determine whether individuals identified as having superior smiles display differences in alignment discrepancies (angulation between interpupillary and commissure line); width-to-length ratios of maxillary anterior teeth; application of the golden proportion (approximately 1.618:1); and number of teeth revealed in an animated smile when compared with an average population. MATERIAL AND METHODS: An Internet search for "best smile" and "celebrity" identified 108 celebrities. Photographs showing smiles within 10 degrees of a frontal view were collected, while photographs of dental students were used for the control group. Alignment discrepancies, widths and lengths of the anterior teeth, and number of teeth revealed in an animated smile were measured with photo-editing software, and ratios were calculated. The groups were compared with repeated-measures ANOVA, the Mann-Whitney U test, and the Wilcoxon signed-rank test (α=.05). RESULTS: Usable photographs were obtained for 90 celebrities (58 women, 32 men) and compared with photographs of 97 dental students (54 women, 43 men). Statistically significant differences were found for alignment discrepancies (celebrities 0.97, students 1.25, P=.034) and for the number of teeth displayed (P=.049); 22.2% of the celebrities revealed 12 teeth, versus 6.2% of the students. In both groups, significant differences from the golden ratio (1.618:1) for the width of the central incisor/lateral incisor right and left and for the width of the lateral incisor/canine right and left were observed through 95% confidence intervals. Sex and left-right were nonsignificant factors. CONCLUSIONS: Celebrities identified as having a best smile had smaller mean alignment discrepancies and revealed a greater number of teeth in an animated smile than dental students.

Systematic review of cyclosporin A-induced gingival overgrowth and genetic predisposition.

OBJECTIVE: This systematic review aimed to investigate the influence of gene polymorphisms on the development of gingival overgrowth in renal transplant patients treated with cyclosporin A. METHOD AND MATERIALS: Electronic and hand literature searches were conducted by two independent reviewers in MEDLINE-Pubmed, Cochrane Library, ISI Web of Science, and SCOPUS Elsevier for prospective (case-control studies, cohort studies), cross-sectional, and retrospective studies published up to June 2016 (first week) in any language. Data were reviewed and extracted in duplicate independently. Methodologic quality assessment of the included studies was performed during the data extraction process. RESULTS: Due to the estimated high risk of bias and the heterogeneity of the included studies in regards to the variety of medications administered to study patients, a systematic review of the literature and not a meta-analysis of the data was performed. Fourteen articles meeting study inclusion criteria were selected for data extraction that examined the association between various genetic polymorphisms and gingival overgrowth in kidney transplant patients receiving cyclosporin A. Interleukin-1A, interleukin-10, transforming growth factor-ß1 and androgen receptor gene polymorphisms may have a significant effect on an individual susceptibility to cyclosporin A-induced gingival overgrowth in renal transplant patients. CONCLUSION: Genetic polymorphisms seem to affect the development of cyclosporin A-induced gingival overgrowth in renal transplant patients. Pharmacogenetics and pharmacogenomics have the potential to determine the clinical outcome of a medication, the drug efficacy, and adverse drug reactions such as gingival overgrowth.

Limitations and options using resorbable versus nonresorbable membranes for successful guided bone regeneration.

OBJECTIVE: Deficient bony ridges often complicate the implant treatment plan. Several treatment modalities are used to regenerate bone, including guided bone regeneration (GBR). The purpose of this study was to summarize the knowledge on different types of membranes available and currently used in GBR procedures in a staged approach or with simultaneous implant placement. The primary role of the membranes is to exclude epithelial and connective tissue cells from the wound area to be regenerated, and to create and maintain the space into which pluripotential and osteogenic cells are free to migrate. DATA SOURCES: A literature search was performed for articles that were published in English on the topic. A selected number of studies were chosen in order to provide a review of the main characteristics, applications, and outcomes of the different types of membranes. Resorbable membranes are made of natural or synthetic polymers like collagen and aliphatic polyesters. Collagens are the most common type used. They have similar collagen composition to the periodontal connective tissue. Other materials available include human, porcine, and bovine pericardium membranes, human amnion and chorion tissue, and human acellular freeze-dried dermal matrix. Nonresorbable membranes used in GBR include dense-polytetrafluoroethylene (d-PTFE), expanded-polytetrafluoroethylene (e-PTFE), titanium mesh, and titanium-reinforced polytetrafluoroethylene. CONCLUSIONS: The most common complication of nonresorbable membranes is exposure, which has detrimental effect on the final outcome with both types of membranes. For vertical bone augmentation procedures, the most appropriate membranes are the nonresorbable. For combination defects, both types result in a successful outcome.

Celebrity smile esthetics assessment: Smile angulation.

STATEMENT OF PROBLEM: Whether deviations in the angulation discrepancy between the intercanine and interpupillary line significantly affect attractiveness is unknown. PURPOSE: The purpose of this prospective study was to quantify dental and facial esthetics to determine whether smile angulation discrepancies in individuals identified as having attractive smiles are smaller than those in the average population. MATERIAL AND METHODS: An Internet search for "best smile" and "celebrity" identified 108 celebrities (Test group). Photographs showing smiles within 10 degrees of a frontal view were gathered. In mannequin testing, small head rotation (<10 degrees) was found not to affect the measurements. Photographs of dental students were used for the control group. The angulation discrepancy between the intercanine and interpupillary line was measured using computer software. Groups were compared using the Mann-Whitney U test (α=.05). RESULTS: Usable photographs were obtained for 94 celebrities (62 women, 32 men) and were compared with photographs of 97 dental students (54 women, 43 men). Significant (P<.01) differences in angulation discrepancy were found, with celebrities having smaller mean angulation discrepancies (0.97 degrees) than dental students (1.33 degrees). The differences between men and women were not statistically significant (P>.05). CONCLUSIONS: Celebrities identified as having "best smile" had significantly smaller mean angulation discrepancies than the control group.

Risk Indicators of Papillary Recession in the Anterior Maxilla.

PURPOSE: The interdental papilla is the portion of the gingiva that occupies the space between two adjacent teeth. When papillary recession occurs, an array of problems arises ranging from phonetics to food impaction and esthetic concerns. The aim of this study was to identify risk indicators for visible papillary recession in the anterior maxilla among a Caucasian population utilizing an advanced analytical approach. MATERIALS AND METHODS: A dataset of 211 adult dentate Caucasian patients that had undergone intraoral assessment of midline papillary recession and extra-oral assessment of visible papillary recession during maximum ("Duchenne") smile was utilized. An enhanced analytical approach was employed to identify risk indicators for papillary recession. RESULTS: Approximately one-third of the participants (38%) demonstrated papillary recession during maximum smile ("visible papillary recession"). An association between sex (male preference) and visible papillary recession was found in this sample population, while age was found to be a risk indicator for papillary recession in individuals over 65 years of age. CONCLUSIONS: Visible midline papillary recession in the maxilla is a highly prevalent clinical entity in Caucasian individuals, thus the development of efficacious treatment modalities for papillary regeneration is necessary. Findings of the present study on risk indicators for visible papillary absence, namely sex and age, may facilitate clinicians in treating patient with compromised interdental aesthetics as well as identifying patients that are in high risk for loss of interdental tissues. CLINICAL SIGNIFICANCE: Findings of the present study on risk indicators for visible papillary absence, namely sex and age, indicate the need for careful assessment and meticulous treatment planning with respect to preservation of the interdental tissues. The consideration of these risk indicators can help dentists to identify patients at risk for papillary recession.

Non-syndromic and syndromic keratocystic odontogenic tumors: systematic review and meta-analysis of recurrences.

BACKGROUND: Keratocystic odontogenic tumors (KCOTs) are locally aggressive benign tumors which occur in the bones of both jaws with a high recurrence rate. The aim of the present study was to define and evaluate the post-treatment recurrence of KCOT lesions in non-syndromic and syndromic patients. METHODS: A systematic review of the literature and meta-analysis was conducted according to the PRISMA statement. Seven electronic databases were searched from their start up to August 2013 for clinical studies on human patients without limitation to year, language or publication status. RESULTS: A total of five case series studies with 323 treated KCOT lesions were included in the quantitative synthesis. The recurrence rate of KCOTs for three treatment forms ranged from 7% to 28%. Comparisons among the various treatments suggest that resection or marsupialization might be associated with fewer recurrences. However, high risk of bias and effect imprecision preclude the making of clinical recommendation. Existing evidence regarding nevoid basal cell carcinoma patients was likewise scarce. CONCLUSIONS: The absence of studies with low risk of bias precludes the making of safe recommendations about the optimal management of KCOTs.