Clinical and patient-reported outcomes of tissue engineering strategies for periodontal and peri-implant reconstruction.

Scientific advancements in biomaterials, cellular therapies, and growth factors have brought new therapeutic options for periodontal and peri-implant reconstructive procedures. These tissue engineering strategies involve the enrichment of scaffolds with living cells or signaling molecules and aim at mimicking the cascades of wound healing events and the clinical outcomes of conventional autogenous grafts, without the need for donor tissue. Several tissue engineering strategies have been explored over the years for a variety of clinical scenarios, including periodontal regeneration, treatment of gingival recessions/mucogingival conditions, alveolar ridge preservation, bone augmentation procedures, sinus floor elevation, and peri-implant bone regeneration therapies. The goal of this article was to review the tissue engineering strategies that have been performed for periodontal and peri-implant reconstruction and implant site development, and to evaluate their safety, invasiveness, efficacy, and patient-reported outcomes. A detailed systematic search was conducted to identify eligible randomized controlled trials reporting the outcomes of tissue engineering strategies utilized for the aforementioned indications. A total of 128 trials were ultimately included in this review for a detailed qualitative analysis. Commonly performed tissue engineering strategies involved scaffolds enriched with mesenchymal or somatic cells (cell-based tissue engineering strategies), or more often scaffolds loaded with signaling molecules/growth factors (signaling molecule-based tissue engineering strategies). These approaches were found to be safe when utilized for periodontal and peri-implant reconstruction therapies and implant site development. Tissue engineering strategies demonstrated either similar or superior clinical outcomes than conventional approaches for the treatment of infrabony and furcation defects, alveolar ridge preservation, and sinus floor augmentation. Tissue engineering strategies can promote higher root coverage, keratinized tissue width, and gingival thickness gain than scaffolds alone can, and they can often obtain similar mean root coverage compared with autogenous grafts. There is some evidence suggesting that tissue engineering strategies can have a positive effect on patient morbidity, their preference, esthetics, and quality of life when utilized for the treatment of mucogingival deformities. Similarly, tissue engineering strategies can reduce the invasiveness and complications of autogenous graft-based staged bone augmentation. More studies incorporating patient-reported outcomes are needed to understand the cost-benefits of tissue engineering strategies compared with traditional treatments.

Involvement of the endocannabinoid system in current and recurrent periodontitis: A human study.

OBJECTIVE: The aim of the present study was to assess if the endocannabinoid system is involved differently in patients with recurrent and non-recurrent periodontal disease and if in sites that have a predisposition for reactivation, levels of anandamide (AEA) change after periodontal therapy. BACKGROUND: Periodontal disease (PD) may be due to a dysregulation of the endocannabinoid system. METHODS: Periodontal patients were recruited, treated for PD and monitored. Gingival samples from these patients with recurrent (n = 10) and non-recurrent (n = 10) periodontal disease were harvested before and after treatment and compared to those of periodontally healthy (n = 10) subjects. Levels of CB1 and CB2, AEA and CBs receptor activation were assessed in healthy and inflamed samples using immunohistochemistry, chromatography and autoradiography. In healed sites, AEA levels were also assessed. RESULTS: The number of CBs in inflamed sites of recurrent patients was significantly higher than in those with non-recurrent disease and also higher than those in healthy subjects. Inflamed sites of recurrent patients had significantly lower CBs receptor activation than those of healthy subjects. Levels of AEA in inflamed sites of non-recurrent patients were significantly higher than those found both in inflamed recurrent sites and in healthy sites. Otherwise, the amount of AEA in healthy subjects and recurrent inflamed sites was similar. After periodontal therapy, levels of AEA were significantly lower in both periodontal groups. In recurrent sites, they resulted significantly lower than in non-recurrent and even in healthy subjects. CONCLUSIONS: The endocannabinoid system seems involved differently in subjects with recurrent and non-recurrent periodontal disease.

Radiographic ratios for classifying furcation anatomy: proposal of a new evaluation method and an intra-rater and inter-rater operator reliability study.

OBJECTIVES: Even if it seems to be an important anatomical parameter for tissue regeneration, few studies in literature evaluate the "mean measure" of root divergence. Most of them are linear measurements, which hardly describe the dental furcation conformation in its entirety. It is left to the subjectivity of the operator deciding whether a furcation is convergent or divergent. The goal of this study is to create a visual evaluation method using specific measurements applied on endo-oral X-rays to overcome these problems, giving a conformation of the entire interradicular space and its divergence. MATERIAL AND METHODS: A user-friendly software (Paint®, Windows10®) was used to take three different measurements on endo-oral radiographs of upper and lower molars. Three blind operators measured 20 radiographs, to analyze the intra- and inter-operator reproducibility of the measurements. Then, the technique was repeated on 250 radiographic images to identify an average value and define a main conformation of the interradicular space. The ratio of these three measurements allowed to develop a new visual evaluation method of the interradicular space. RESULTS: Intra and inter-operator reproducibility was statistically confirmed on a sample of 20 anonymous endo-oral radiographs measured by 3 blind operators, indicating that the measurement technique was not operator dependent. Measurement made on 250 X-rays obtained with this technique permitted to subdivide in five groups the conformation of the interradicular space and define a mean value of the interradicular space. CONCLUSIONS: A new anatomical evaluation of the interradicular space in its entirety, which could help the clinicians in diagnostic and decisional phase in the therapy of furcated molars, can be obtained. CLINICAL RELEVANCE: A pre-operative evaluation of interradicular space conformation could affect therapy treatment choice.

The influence of interradicular anatomy on the predictability of periodontal regenerative therapy of furcation defects: a retrospective, multicenter clinical study.

BACKGROUND: The relationship between the anatomy of the interradicular space and success in regenerative therapy of furcation defects is discussed in this paper. The goal of this retrospective, multicenter clinical study is to clinically evaluate the relationship between the interradicular conformation and regenerative therapy success with the use of a novel measurement method. METHODS: One hundred thirty-eight radiographs of mandibular molars with furcation defects that had been treated with regenerative therapy were collected from six clinical centers. Data on the type of therapy and clinical parameters before and after treatment (follow-up of at least 12 months) were collected. The radiographs (before surgery and at least 12 months postoperatively) were measured with a visual evaluation method by a blind operator using graphics software. RESULTS: Success, defined as a reduction in horizontal and vertical furcation involvement, decrease in probing depths, and increase in clinical attachment level, was statistically assessed on 138 regenerated molars sites and were related to clinical variables such as age, sex, center, and treatment. No correlation was found between success in regenerative therapy and the conformation of the interradicular space, measured with a visual ratio method and a standard linear measurement. At the univariate analysis, the parameters that had a correlation with success were center, extent of furcation involvement, treatment, and sex. The use of enamel matrix derivative (EMD) seemed to be the most favorable therapy, with increase in CAL gain and reduction of vertical or horizontal furcation involvement. CONCLUSIONS: The regenerative outcome was not significantly influenced by the anatomy of furcation. The center, the degree of furcation involvement, sex, and treatment (EMD) were significantly associated with higher success of periodontal regeneration.

Soft tissue phenotype modification predicts gingival margin long-term (10-year) stability: Longitudinal analysis of six randomized clinical trials.

AIM: To assess the prognostic value of soft tissue phenotype modification following root coverage procedures for predicting the long-term (10-year) behaviour of the gingival margin. MATERIALS AND METHODS: Participants from six randomized clinical trials on root coverage procedures at the University of Michigan were re-invited for a longitudinal evaluation. Clinical measurements were obtained by two calibrated examiners. A data-driven approach to model selection with Akaike information criterion (AIC) was carried out via multilevel regression analyses and partial regression plotting for changes in the level of the gingival margin over time and interactions with the early (6-month) results of soft tissue phenotypic modification. RESULTS: One-hundred and fifty-seven treated sites in 83 patients were re-assessed at the long-term recall. AIC-driven model selection and regression analyses demonstrated that 6-month keratinized tissue width (KTW) and gingival thickness (GT) influenced the trajectory of the gingival margin similarly in a concave manner; however, GT was the driving determinant that predicted significantly less relapse in the treatments, with stability of the treated gingival margin obtained beyond values of 1.46 mm. CONCLUSIONS: Among a compliant patient cohort, irrespective of the rendered therapy, the presence of at least 1.5 mm KTW and 1.46 mm GT was correlated with the long-term stability of the gingival margin.

Autologous connective tissue graft or xenogenic collagen matrix with coronally advanced flaps for coverage of multiple adjacent gingival recession. 36-month follow-up of a randomized multicentre trial.

AIM: To report the 36-month follow-up of a trial comparing the adjunct of a xenogenic collagen matrix (CMX) or connective tissue graft (CTG) to coronally advanced flaps (CAF) for coverage of multiple adjacent recessions. MATERIAL AND METHODS: 125 subjects (61 CMX) with 307 recessions in 8 centres from the parent trial were followed-up for 36 months. Primary outcome was change in position of the gingival margin. Multilevel analysis used centre, subject and tooth as levels and baseline parameters as covariates. RESULTS: No differences were observed between the randomized and the follow-up population. Average baseline recession was 2.6 ± 1.0 mm. 3-year root coverage was 1.5 ± 1.5 mm for CMX and 2.0 ± 1.0 mm for CTG (difference of 0.32 mm, 95% CI from -0.02 to 0.65 mm). The upper limit of the confidence interval was over the non-inferiority margin of 0.25 mm. No treatment differences in position of the gingival margin were observed between 6- and 36-month follow-up (difference 0.06 mm, 95% CI -0.17 to 0.29 mm). CONCLUSION: CMX was not non-inferior with respect to CTG in multiple adjacent recessions. No differences in stability of root coverage were observed between groups and in changes from 6 to 36 months. Previously reported shorter time to recovery, lower morbidity and more natural appearance of tissue texture and contour observed for CMX in this trial are also relevant in clinical decision-making.

Implant soft tissue Dehiscence coverage Esthetic Score (IDES): A pilot within- and between-rater analysis of consistency in objective and subjective scores.

OBJECTIVES: To introduce an esthetic index for assessing the outcomes of peri-implant soft tissue dehiscence/deficiency (PSTD) coverage and test its within- and between-reviewer reliability. MATERIALS AND METHODS: Photographs of 51 single PSTDs at baseline and after treatment were provided to four periodontists from three centers. The examiners were asked to rate each case at two timepoints with the Implant soft tissue Dehiscence/deficiency coverage Esthetic Score (IDES) that involved the evaluation of the post-treatment level of the soft tissue margin, peri-implant papillae height, mucosa color, and mucosa appearance (summing up to a total score of 10). Variance components analysis was conducted using multilevel regression fit in a Bayesian framework for obtaining uncertainty intervals for fractional variance contributions and intraclass correlation values (ICC) of the IDES, and for each of its four clinical variables. RESULTS: Regression models showed reproducible esthetic evaluation among the examiners (inter-reliability) and negligible intra-reviewer variability (assessment of the same case at different timepoints). The ICC for the variability in the assessment of the overall IDES was 0.86, and for the individual components ranged from 0.78 to 0.87. Additionally, there was a strong similarity between the raters' IDES values, and their subjective esthetic response, by the same raters. CONCLUSION: The IDES showed persistent judgment among the 4 reviewers, and only a slight intra-reviewer variability across timepoints. Within its limitations, this study suggests that the proposed novel score can be a reliable tool for evaluating the esthetic outcomes of PSTD coverage, which can aid in standardization of esthetic assessments following the treatment of a PSTD.

Comparison between a xenogeneic dermal matrix and connective tissue graft for the treatment of multiple adjacent gingival recessions: a randomized controlled clinical trial.

AIM: To compare the outcomes of modified coronally advanced flap (mCAF) combined with either xenogeneic dermal matrix (XDM) or connective tissue graft (CTG) for the treatment of multiple adjacent gingival recessions (MAGRs). MATERIALS AND METHODS: Forty-two patients, in whom 130 maxillary (MAGRs) of type (RT1) were found, were randomly allocated to the two groups. Clinical, esthetic, and patient-centered outcomes were evaluated at baseline, 6, and 12 months post-treatment. RESULT: Group CAF+ CTG exhibited a higher mean root coverage value (mRC) (91.79%) (primary outcome variable) than group CAF+XDM (80.19%) without statistically significant difference at 12 months (p=0.06). The control group also had significantly higher percentage of teeth in which complete root coverage (CRC) and mean gain of gingival thickness (GT) were achieved, than the test group (p<0.05). With respect to patient-centered outcomes, patients of the test group reported having experienced significantly less pain than those of the control group until 7 days (p<0.05). Both surgical approaches were capable of significantly decreasing dentin hypersensitivity (p<0.05). No difference between groups was found in the esthetic score analysis (p>0.05). Mean surgical time was lower in the test group (p<0.05). CONCLUSION: The two treatments showed similar mRC. However, CAF+CTG was superior to CAF+XDM in providing CRC and in gaining GT. CAF+XDM demonstrated advantages over CAF+CTG with regard to patient morbidity and surgical time. CLINICAL RELEVANCE: Application of XDM provided a better patient experience and shortened the time to recovery after coronally advanced flaps for coverage of multiple adjacent recessions. However, CTG resulted in improved percentages of complete root coverage. TRIAL REGISTRATION: Brazilian Clinical Trials Registry (REBEC) number: RBR-974c9j.

Gingival phenotype assessment methods and classifications revisited: a preclinical study.

OBJECTIVE: To compare gingival phenotype assessment methods based on soft tissue transparency on different backgrounds and assessor experience levels. METHODS: For this purpose, 24 gingival specimens were retrieved from pig jaws with tissue thicknesses from 0.2 to 1.25 mm. Three methods were assessed: periodontal probe PCP12 (thin/thick), double-ended periodontal probe DBS12 (thin/moderate/thick) and colour-based phenotype probe CBP (thin/moderate/thick/very thick). Each sample was photographed with each probe underneath and categorized whether the probe was visible or not using different coloured backgrounds. To measure experience level influence, dentists, dental undergraduate students and laypersons (n = 10/group) performed the evaluation. RESULTS: PCP12 probe showed a threshold between 0.4 and 0.5 mm. To distinct between thin and moderate thick gingiva, a comparable range for DBS12 was found while moderate thickness was between 0.5 and 0.8 mm and for thick above 0.8 mm. CBP also showed a comparable threshold of 0.5 mm for thin versus moderate as compared with the other methods; above 0.8 mm, predominantly a very thick tissue was measured. In general, the background colour had a minor impact on PCP12 and DBS12, and investigator experience showed no clear influence on GP assessment. CONCLUSION: Based on probe transparency and within the limitation of a preclinical study, we suggest GP differentiation into three entities: thin (< 0.5 mm; high risk), moderate (0.5-0.8 mm; medium risk) and thick (> 0.8 mm; low risk). CLINICAL RELEVANCE: All three GP assessment methods are easy to perform and seem to have a high predictive value with a three entities classification for DBS12 and CBP.

Aesthetic-And patient-related outcomes following root coverage procedures: A systematic review and network meta-analysis.

BACKGROUND: Aim of this systematic review (SR) of randomized controlled trials (RCTs) was to evaluate effect of different flap designs and graft materials for root coverage, in terms of aesthetics, patient satisfaction and self-reported morbidity (post-operative pain/discomfort). MATERIAL AND METHODS: A comprehensive literature search was performed. A mixed-modelling approach to network meta-analysis was utilized to formulate direct and indirect comparisons among treatments for Root Coverage Esthetic Score (RES), with its individual components, and for subjective patient-reported satisfaction and post-operative pain/discomfort (visual analogue scale (VAS) of 100). RESULTS: Twenty-six RCTs with a total of 867 treated patients (1708 recessions) were included. Coronally Advanced Flap (CAF) + Connective Tissue Graft (CTG) (0.74 (95% CI [0.24, 1.26], p = .005)), Tunnel (TUN) + CTG (0.84 (95% CI [0.15, 1.53]), p = .01) and CAF + Graft substitutes (GS) (0.55 (95% CI [0.006, 1.094], p = .04)) were significantly associated with higher RES than CAF. No significant difference between CAF + CTG and TUN + CTG was detected (0.09 (95% CI [-0.54, 0.72], p = .77)). Addition of CTG resulted in less natural tissue texture (-0.21 (95% CI [-0.34, -0.08]), p = .003) and gingival colour (-0.06 (95% CI [-0.12, -0.03], p = .03)) than CAF. CTG techniques were associated with increased morbidity. CONCLUSIONS: Connective tissue graft procedures showed highest overall aesthetic performance for root coverage, although graft integration might impair soft tissue colour and appearance. Additionally, CTG-based techniques were also correlated with a greater patient satisfaction and morbidity.

Acellular dermal matrix and coronally advanced flap or tunnel technique in the treatment of multiple adjacent gingival recessions. A 12-year follow-up from a randomized clinical trial.

AIM: To evaluate the long-term outcomes of Acellular Dermal Matrix (ADM) with Coronally Advanced Flap (CAF) or Tunnel technique (TUN) in the treatment of multiple adjacent gingival recessions (MAGRs). MATERIAL AND METHODS: Nineteen of the original 24 patients contributing to a total number of 33 sites for CAF and 34 for TUN were available for the 12 years follow-up examination. Recession depth, mean root coverage (mRC), keratinized tissue width (KTW), gingival thickness (GT) were evaluated and compared with baseline values and 6-months results. Regression analysis was performed to identify factors related to the stability of the gingival margin. RESULTS: A highly significant drop in mRC was observed for both groups from the 6 months timepoint to the 12 years recall (p < .001). While there were no statistically significant differences between the two groups in terms of Clinical Attachment Level (CAL), KTW, GT changes and Root Coverage Esthetic Score at each timepoint (p > .05). KTW ≥ 2 mm and GT ≥ 1.2 mm at 6-months were two predictors for stability of the gingival margin (p = .03 and p = .01, respectively). CONCLUSIONS: A significant relapse of the gingival margin of MAGRs treated with CAF or TUN + ADM was observed after 12 years.

CEMP-1 Levels in Periodontal Wound Fluid during the Early Phase of Healing: Prospective Clinical Trial.

OBJECTIVES: Cementogenesis seems to be significantly compromised during tissue inflammation. In dental practice, surgical procedures are performed with the aim to regenerate periodontium including cementum. However, inflammation that occurs during the initial healing phases after surgery may impair regeneration of this tissues. The aim of the present study was to assess if surgical procedures designed to regenerate periodontium might affect levels of cementum protein-1 (CEMP-1) in periodontal wound fluid during early phase of healing. MATERIALS AND METHODS: In 36 patients, 18 intrabony periodontal defects were treated with regenerative therapy (REG group) and 18 suprabony periodontal defects were treated with open flap debridement (OFD group). In the experimental sites, gingival crevicular fluid was collected immediately before surgery, and periodontal wound fluid was collected 4, 7, 14, and 21 days after surgery. CEMP-1 levels were detected by indirect enzyme-linked immunosorbent assay technique. RESULTS: At the analysis, it resulted that there was a significant average difference in CEMP-1 values between the REG and OFD groups at baseline (p = 0.041), the CEMP-1-modeled average in the OFD group was lower by 0.45 ng/ml. There was a significant trend in CEMP-1 over time, and this trend was different among the 2 groups: the REG group showed a statistically significant rising CEMP-1 trend (0.18 ng/ml a week p = 0.012), while the OFD had a trend that was significantly lower (-0.22 ng/ml a week compared to the REG group trend p = 0.023), the OFD group lost on average 0.05 ng/ml a week. In REG sites, GCF protein levels resulted also related to clinical parameters. CONCLUSIONS: During the initial inflammatory phase of periodontal healing, CEMP-1 levels decrease regardless of the surgical protocol applied. The surgical procedures used to regenerate periodontal tissue are able to reverse this trend and to induce significant increase of CEMP-1 in periodontal wound fluid after the first week postop.

Pain perception following epithelialized gingival graft harvesting: a randomized clinical trial.

OBJECTIVES: The aim of this study was to compare the effects of a hemostatic collagen sponge and a collagen sponge sealed with a bio-adhesive material on the palatal donor sites with the purpose of minimizing postoperative pain after epithelialized gingival graft (EGG) harvesting. MATERIAL AND METHODS: The present study consisted of 44 EGGs harvested in 44 patients. In the control group, a hemostatic collagen sponge was applied over the palatal wound, while the test group was treated with additional cyanoacrylate. Patients were observed for 14 days, evaluating the pain level by using the visual analogic scale. The consumption of analgesic during the postoperative period, the willingness for retreatment and the characteristic of the graft were also analyzed. RESULTS: Statistically significant differences in pain perception were found between test and control groups in each of the studied days (p < 0.01). Analgesic consumption was lower in the test group (p < 0.01). Graft width < 14 mm was found to be associated with lower discomfort (p < 0.01). CONCLUSIONS: Adding an additional layer of cyanoacrylate over a hemostatic collagen sponge on the palatal wound following EGG harvesting was found to be successful in minimizing the postoperative discomfort and the need for analgesics. CLINICAL RELEVANCE: Postoperative pain after palatal tissue harvesting can be successfully minimized if the donor site open wound is protected with an external layer of cyanoacrylate over a collagen sponge.

Influence of suturing technique on marginal flap stability following coronally advanced flap: a cadaver study.

OBJECTIVES: The outcomes of periodontal soft tissue root coverage procedures can be influenced by a variety of different factors. Following coronally advanced flap (CAF), the impact of marginal flap stability (MFS) through the employment of specific suturing techniques has not yet been investigated. The purpose of this study was to compare the MFS of CAF following three different suture techniques. METHODS: Fifty-six CAF procedures were performed on seven fresh human cadaver heads. The MFS following simple interrupted, single sling or sling and tag (SAT) suture techniques were investigated through a specific tool involving a load cell-based recording device. RESULTS: A highly statistically significant MFS was observed for sling and SAT sutures compared to the simple interrupted suture (p < 0.001). SAT suture technique was related to the greatest MFS (p < 0.001). The addition of sutures to the vertical releasing incision was able to provide a greater MFS compared to the suturing of the papillae alone (p < 0.001). No statistically significant difference was observed with regard to the suturing sequence between the two sling groups when the vertical incisions were sutured before or after the surgical papillae (p > 0.05). Linear regression model showed a positive correlation between thicker gingival tissue and MFS changes (p < 0.001). CONCLUSIONS: Suturing technique highly affects the MFS following CAF on cadavers. Flap thickness was shown to be a positive predictor for flap stability. CLINICAL RELEVANCE: Within the limitation of this study, the suturing of CAF with the SAT technique may provide higher MFS. However, clinical studies are necessary to validate these findings.

Predictor factors for long-term outcomes stability of coronally advanced flap with or without connective tissue graft in the treatment of single maxillary gingival recessions: 9 years results of a randomized controlled clinical trial.

AIM: To assess the clinical outcomes 9 years after the surgical treatment of single maxillary gingival recessions and identify predictors for long-term gingival margin stability. MATERIALS AND METHODS: Twenty-five gingival recessions (Miller Class I and II) were randomly treated with Coronally Advanced Flap (CAF) plus Connective Tissue Graft (CTG) or CAF alone. Outcomes included complete root coverage (CRC), recession reduction (REC), keratinized tissue (KT) gain and dentin hypersensitivity, and were evaluated at 6 months, 1 and 9 years. Multilevel analysis was performed to identify predictors for long-term gingival margin stability. RESULTS: Baseline gingival recession was 2.4 ± 0.8 mm and 2.4 ± 1.0 mm in the CAF + CTG and in the CAF-treated sites, respectively (p = 0.693). The chance to gain and preserve CRC over time is equal to 70% in the CAF + CTG group (Relative Risk [RR] = 1.70, 95% CI [0.84-3.45]; adjusted RR = 1.48, 95% CI [0.61-3.62]). Using the CTG, an increase in KT was recorded 9 years after the surgery (p = 0.019). An OR of 0.12 (p = 0.022) of not achieving CRC was observed in cases with non-carious cervical lesions (NCCL) compared to cases without NCCL. CONCLUSION: Both treatment modalities demonstrated stability over time. Additional use of CTG provided a greater increase in KT. The presence of NCCL negatively affected CRC and REC.

Xenogenic collagen matrix or autologous connective tissue graft as adjunct to coronally advanced flaps for coverage of multiple adjacent gingival recession: Randomized trial assessing non-inferiority in root coverage and superiority in oral health-related quality of life.

AIM: To evaluate the non-inferiority of the adjunct of a xenogeneic collagen matrix (CMX) or connective tissue graft (CTG) to coronally advanced flaps (CAF) for coverage of multiple adjacent recessions and compare superiority in patient-reported outcomes (PROM). MATERIAL AND METHODS: One hundred and eighty-seven subjects (92 CMX) with 485 recessions in 14 centres were randomized and followed up for 6 months. Patients filled daily diaries for 15 days to monitor patient-reported experience. The primary outcome was changed in position of the gingival margin. Multilevel analysis used centre, subject and tooth as levels and baseline parameters as covariates. RESULTS: Average baseline recession was 2.5 ± 1.0 mm. The surgery was 15.7 min shorter (95%CI from 11.9 to 19.6, p < .0001) and perceived lighter (11.9 VAS units, 95%CI from 4.6 to 19.1, p = .0014) in CMX subjects. Time to recovery was 1.8 days shorter in CMX. Six-month root coverage was 1.7 ± 1.1 mm for CMX and 2.1 ± 1.0 mm for CTG (difference of 0.44 mm, 95%CI from 0.25 to 0.63 mm). The upper limit of the confidence interval was over the non-inferiority margin of 0.25 mm. Odds of complete root coverage were significantly higher for CTG (OR = 4.0, 95% CI 1.8-8.8). CONCLUSION: Replacing CTG with CMX shortens time to recovery and decreases morbidity, but the tested generation of devices is probably inferior to autologous CTG in terms of root coverage. Significant variability in PROMs was observed among centres.

Immediate versus delayed implant placement after anterior single tooth extraction: the timing randomized controlled clinical trial.

AIM: To compare need for bone augmentation, surgical complications, periodontal, radiographic, aesthetic and patient reported outcomes in subjects receiving implant placement at the time of extraction (Immediate Implant) or 12 weeks thereafter. METHODS: Subjects requiring single tooth extraction in the anterior and premolar areas were recruited in seven private practices. Implant position and choice of platform were restoratively driven. Measurements were performed by calibrated and masked examiners. RESULTS: IMI was unfeasible in 7.5% of cases. One hundred and 24 subjects were randomized. One implant was lost in the IMI group. IMI required bone augmentation in 72% of cases compared with 43.9% for delayed (p = 0.01), while wound failure occurred in 26.1% and 5.3% of cases, respectively (p = 0.02). At 1 year, IMI had deeper probing depths (4.1 ± 1.2 mm versus 3.3 ± 1.1 mm, p < 0.01). A trend for greater radiographic bone loss was observed at IMI over the initial 3-year period (p-trend < 0.01). Inadequate pink aesthetic scores were obtained in 19% of delayed and in 42% of IMI implant cases (p = 0.03). No differences in patient reported outcomes were observed. CONCLUSIONS: Immediate implant placement should not be recommended when aesthetics are important, IMI should be limited to selected cases. Longer follow-up is needed to assess differences in complication rates.

Evaluation of DNA methylation of inflammatory genes following treatment of chronic periodontitis: A pilot case-control study.

OBJECTIVE: To evaluate the influence of periodontal therapy on DNA methylation in patients with chronic periodontitis as compared to healthy individuals. MATERIAL AND METHODS: Twenty patients were enrolled into two groups: (i) 10 diagnosed as clinically healthy; and (ii) 10 diagnosed with chronic periodontitis. Clinical measures were recorded and gingival biopsies were harvested at baseline (both patient groups) and at 2 and 8 weeks post-baseline for diseased individuals. Molecular DNA methylation analysis was performed by pyrosequencing for the putative inflammation-associated genes LINE-1, COX-2, IFN-γ and TNF-α. Random-intercept linear regression models were applied to evaluate methylation levels across groups at baseline and the methylation changes over time in the diseased and normal tissues. RESULTS: Periodontal therapy did not influence gene expression methylation of TNF-α, IFN-γ and LINE-1 levels at normal and periodontitis sites over time. However, it significantly reduced COX-2 methylation levels comparable to healthy individuals at both 2 and 8 weeks post-treatment (p < .05). CONCLUSIONS: Periodontal therapy resets the DNA methylation status of inflammatory gene for COX-2 in patients with periodontal disease. DNA methylation levels of TNF-α, IFN-γ and LINE-1 were sustained in periodontitis sites despite therapy. Future studies should consider an expanded panel of inflammatory genes over time. (ClinicalTrials.gov NCT02835898).

Pleural malignant mesothelioma in dental laboratory technicians: A case series.

Asbestos was used in dentistry as a binder in periodontal dressings and as lining material for casting rings and crucible. However, until now, only one case of malignant mesothelioma with occupational exposure to asbestos in dental practice has been reported. We present 4 pleural mesotheliomas out of 5344 cases identified in Lombardy, Italy, in 2000-2014. Three men had been working as dental laboratory technicians, with asbestos exposure for 10, 34, and 4 years, and one woman had been helping her husband for 30 years in manufacturing dental prostheses. The men described the use of asbestos as a lining material for casting rings, while the woman was not able to confirm this use. We confirm the association of malignant mesothelioma with dental technician work. Dental technicians suffering from mesothelioma should be questioned about past occupational asbestos exposure.

Twenty years of enamel matrix derivative: the past, the present and the future.

BACGROUND: On June 5th, 2015 at Europerio 8, a group of leading experts were gathered to discuss what has now been 20 years of documented evidence supporting the clinical use of enamel matrix derivative (EMD). Original experiments led by Lars Hammarström demonstrated that enamel matrix proteins could serve as key regenerative proteins capable of promoting periodontal regeneration including new cementum, with functionally oriented inserting new periodontal ligament fibres, and new alveolar bone formation. This pioneering work and vision by Lars Hammarström has paved the way to an enormous amount of publications related to its biological basis and clinical use. Twenty years later, it is clear that all these studies have greatly contributed to our understanding of how biologics can act as mediators for periodontal regeneration and have provided additional clinical means to support tissue regeneration of the periodontium. AIMS: This review article aims to: (1) provide the biological background necessary to understand the rational for the use of EMD for periodontal regeneration, (2) present animal and human histological evidence of periodontal regeneration following EMD application, (3) provide clinically relevant indications for the use of EMD and (4) discuss future avenues of research including key early findings leading to the development of Osteogain, a new carrier system for EMD specifically developed with better protein adsorption to bone grafting materials.