Soft-Tissue Phenotype as a Risk Indicator of Peri-Implantitis and Peri-Implant Soft-Tissue Dehiscence-A Cross-Sectional Study.

AIM: To investigate the association, as well as to characterize the associated panel of pro- and anti-inflammatory markers, between the different components of the peri-implant phenotype and the presence of peri-implantitis/peri-implant soft-tissue dehiscence (PISTD). MATERIALS AND METHODS: A total of 324 implants in 112 patients were included. The following components of the peri-implant phenotype were clinically measured through the use of a manual periodontal probe or a digital calliper: keratinized mucosa width (PIKM-W), mucosal thickness (MT), attached mucosa (AM) and vestibulum depth (VD). The presence of peri-implantitis and PISTD was assessed through clinical and radiographic examination. Mixed-models logistic regression analyses were performed to analyse the association between peri-implant phenotype and the presence of peri-implantitis or PISTD, adjusting for relevant confounders. Multiplex immunoassays were employed to evaluate the peri-implant crevicular fluid levels of a panel of pro- and anti-inflammatory markers. RESULTS: Peri-implant health, peri-implant mucositis and peri-implantitis were diagnosed in 36.6%, 21.4% and 42% of the patients (classified according to their worst implant) and 35.2%, 34.3%, and 30.5% of the implants, respectively. In the multi-level multiple regression model, the absence of PIKM-W (odds ratio [OR] = 9.24; 95% CI: 2.73-31.28), the absence of attached mucosa (OR = 19.58; 95% CI: 6.12-62.56) and a reduced (<4 mm) vestibulum depth (OR = 2.61; 95% CI: 1.05-6.48) were associated with peri-implantitis. Similarly, the absence of PIKM-W (OR = 6.32; 95% CI: 1.67-23.83), a thin (<2 mm) mucosa (OR = 157.75; 95% CI: 14.06-1769.9) and a reduced vestibulum depth (OR = 3.32; 95% CI: 1.02-10.84) were associated with the presence of PISTD. Implants with PIKM-W = 0 mm showed statistically significantly higher levels of interferon-γ in both regular (≥2 maintenance/year) and irregular (<2 maintenance/year) compliers (p = 0.046 and p = 0.012). In irregular compliers, the absence of PIKM-W was also associated with statistically significantly higher levels of interleukin (IL)-1ß and IL-21 (p = 0.016, p = 0.046). These associations were independent of the effect of relevant confounders (e.g., plaque, compliance with maintenance, etc.). CONCLUSIONS: Within their limits, the present findings indicate that (a) peri-implant soft-tissue phenotype appears to be associated with the presence of peri-implantitis and PISTD, and (b) in the absence of PIKM-W, the inflammatory response seems to be dysregulated and the soft-tissue remodelling up-regulated.

Effect of Coenzyme Q10 on early wound healing after recession coverage surgery with the modified coronally advanced tunnel technique and a connective tissue graft: A 6-month, triple-blinded, randomized, placebo-controlled pilot trial.

OBJECTIVES: Coenzyme Q10 (CoQ10) or ubiquinone is one of a cell's most important electron carriers during oxidative phosphorylation and many other cellular processes. As a strong anti-oxidant with further anti-inflammatory effects CoQ10 is of potential therapeutical value. The aim of this randomized controlled clinical trial was to investigate the effect of topical CoQ10 on early wound healing after recession coverage surgery using the modified coronally advanced tunnel (MCAT) and palatal connective tissue graft (CTG). MATERIALS AND METHODS: Thirty patients with buccal gingival recessions were evaluated after being randomly allocated to: 1) MCAT and CTG with topical application of a coenzyme Q10 spray for 21 days or 2) MCAT and CTG with placebo spray. Wound healing was evaluated by the early wound healing index (EHI). Patient-reported pain was analyzed by a 100-mm visual analogue scale (VAS) at day 2, 7, 14 and 21 post-surgically. Mean recession coverage, gain of keratinized tissue and esthetic outcomes were assessed at 6 months. RESULTS: EHI and pain scores showed no significant differences. Time to recovery defined as VAS<10 mm was shorter in the test group. Mean root coverage after 6 months was 84.62 ± 26.57% and 72.19 ± 26.30% for test and placebo, p=0.052. Complete root coverage was obtained in 9 (60%) test and in 2 (13.3%) placebo patients. Increase in keratinized tissue width and esthetical outcomes were similar for both groups. CONCLUSION: CoQ10 had no significant effect on early wound healing and on mean root coverage after 6 months. CLINICAL RELEVANCE: Early wound healing: in young healthy patients with no inflammatory oral conditions topical CoQ10 does not improve early healing.

Nano-superhydrophilic and bioactive surface in poor bone environment. Part 1: transition from primary to secondary stability. A controlled clinical trial : Bioactive implant surfaces in poor density bone.

OBJECTIVES: Bioactive surfaces were designed to increase the interaction between the surface and the cells. This may speed up the biological stability and loading protocols. MATERIALS AND METHODS: 36 patients with D3-D4 bone density were recruited and allocated into two groups. 30 bioactive (test group) and 30 traditional (control group) surfaced implants were placed. Insertion torque value (Ncm), insertion torque curve integral (cumulative torque, Ncm), torque density (Ncm/sec), implant stability quotient (ISQ) measured at three timepoints (baseline (T0), 30 (T30) and 45 (T45) days after surgery), and marginal bone loss (MBL) at 6 months of loading were assessed. RESULTS: The mean ISQ and standard deviation at T0, T30, T45 were respectively 74.57 ± 7.85, 74.78 ± 7.31, 74.97 ± 6.34 in test group, and 77.12 ± 5.83, 73.33 ± 6.13, 73.44 ± 7.89 in control group, respectively. Data analysis showed significant differences between groups in ΔISQ at T0-T30 (p = 0.005) and T30-T45 (p = 0.012). Control group showed a significant decrease in ISQ at T30 (p = 0.01) and T45 (p = 0.03) compared to baseline, while no significant change was observed in test group. Due to the stability of the ISQ value ≥ 70, 26 test group and 23 control group implants were functionally loaded after 45 days. Conversely, due to the ISQ < 70 at T45, four test group implants and one control group implant were loaded after 90 days, and 6 control group implants were loaded after 180 days. Neither insertion torque nor ISQ at baseline were correlated with bone density (in Hounsfield units). There was no significant correlation between cumulative torque and ISQ at baseline. There was a significant positive slope in the correlation between torque density and ISQ at baseline, more accentuated in D3 than D4. This correlation remained significant for the test group in D3 bone at day 30 and 45 (p < 0.01 in both time frames), but not in D4 bone, and it was not significant in CG. CONCLUSIONS: The bioactive surface showed better behavior in terms of implant stability in D3-D4 bone quality in the early stages of bone healing. Clinical relevance This study demonstrated that the transition from primary to secondary stability is improved using bioactive surface, especially in cases of poor bone environment (D3/D4 bone).

Autogenous graft versus collagen matrices for peri-implant soft tissue augmentation. A systematic review and network meta-analysis.

OBJECTIVE: The primary objective of this review is to compare autogenous soft tissue grafts (connective tissue graft - CTG and free gingival graft-FGG) with different type of matrices (acellular dermal matrix-ADM, xenograft collagen matrix-XCM, volume-stable collagen matrix-VCMX) used to increase peri-implant soft tissues. MATERIALS AND METHODS: A search on electronic databases was performed to identify randomized and non-randomized controlled trials (RCTs and CCTs, respectively) with either parallel or split-mouth design, and treating ≥ 10 patients. A network meta-analysis (NMA) was used to compare different matrices. Soft tissue thickness dimensional changes and keratinized width (KMW) changes were the primary outcome measures. The secondary outcomes were to evaluate: a) PROMs; b) volumetric changes; c) surgical operating time; and d) different periodontal measurements. RESULTS: A total of 23 studies were included in the qualitative analysis, and 16 studies (11 RCTs and 5 CCTs) in the quantitative analysis. A total of N = 573 sites were evaluated for NMA. CTG resulted the best material for increasing peri-implant soft tissue thickness, at 180 and 360 days after surgery. The use of an ADM showed good results for buccal thickness increase, primarily in the first three months after surgery. Vestibuloplasty + FGG resulted in the most effective technique for peri-implant KMW augmentation, after 180 days. CONCLUSIONS: While CTG demonstrated better performance in all the comparison and FGG showed to be the best graft to increase keratinized mucosa up to 90 days, ADM and VCMX may be used to increase soft tissue horizontal thickness with lower patients' morbidity. LIMITATIONS: The limits of this NMA are the following: a) limited number of included studies; b) high heterogeneity among them (number of patients, treatment sites, surgical techniques, outcome measures, and follow-ups). CLINICAL RELEVANCE: Many studies compared the efficacy of autogenous and non-autogenous grafts in terms of gingival thickness, volume, and keratinized width increase. However, there is still not clear overall evidence on this topic. This NMA helps clinicians to choose the right material in different peri-implant soft tissue procedures. Recommendations for future studies are mandatory.

Understanding exosomes: Part 2-Emerging leaders in regenerative medicine.

Exosomes are the smallest subset of extracellular signaling vesicles secreted by most cells with the ability to communicate with other tissues and cell types over long distances. Their use in regenerative medicine has gained tremendous momentum recently due to their ability to be utilized as therapeutic options for a wide array of diseases/conditions. Over 5000 publications are currently being published yearly on this topic, and this number is only expected to dramatically increase as novel therapeutic strategies continue to be developed. Today exosomes have been applied in numerous contexts including neurodegenerative disorders (Alzheimer's disease, central nervous system, depression, multiple sclerosis, Parkinson's disease, post-traumatic stress disorders, traumatic brain injury, peripheral nerve injury), damaged organs (heart, kidney, liver, stroke, myocardial infarctions, myocardial infarctions, ovaries), degenerative processes (atherosclerosis, diabetes, hematology disorders, musculoskeletal degeneration, osteoradionecrosis, respiratory disease), infectious diseases (COVID-19, hepatitis), regenerative procedures (antiaging, bone regeneration, cartilage/joint regeneration, osteoarthritis, cutaneous wounds, dental regeneration, dermatology/skin regeneration, erectile dysfunction, hair regrowth, intervertebral disc repair, spinal cord injury, vascular regeneration), and cancer therapy (breast, colorectal, gastric cancer and osteosarcomas), immune function (allergy, autoimmune disorders, immune regulation, inflammatory diseases, lupus, rheumatoid arthritis). This scoping review is a first of its kind aimed at summarizing the extensive regenerative potential of exosomes over a broad range of diseases and disorders.

Understanding exosomes: Part 3-therapeutic + diagnostic potential in dentistry.

Exosomes are the smallest subset of extracellular signaling vesicles secreted by most cells with the ability to communicate with other tissues and cell types over long distances. Their use in regenerative medicine has gained tremendous momentum recently due to their ability to be utilized as therapeutic options for a wide array of various diseases. Over 5000 publications are currently being published on this topic yearly, many of which in the dental space. This extensive review article is the first scoping review aimed at summarizing all therapeutic uses of exosomes in regenerative dentistry. A total of 944 articles were identified as using exosomes in the dental field for either their regenerative/therapeutic potential or for diagnostic purposes derived from the oral cavity. In total, 113 research articles were selected for their regenerative potential (102 in vitro, 60 in vivo, 50 studies included both). Therapeutic exosomes were most commonly derived from dental pulps, periodontal ligament cells, gingival fibroblasts, stem cells from exfoliated deciduous teeth, and the apical papilla which have all been shown to facilitate the regenerative potential of a number of tissues including bone, cementum, the periodontal ligament, nerves, aid in orthodontic tooth movement, and relieve temporomandibular joint disorders, among others. Results demonstrate that the use of exosomes led to positive outcomes in 100% of studies. In the bone field, exosomes were found to perform equally as well or better than rhBMP2 while significantly reducing inflammation. Periodontitis animal models were treated with simple gingival injections of exosomes and benefits were even observed when the exosomes were administered intravenously. Exosomes are much more stable than growth factors and were shown to be far more resistant against degradation by periodontal pathogens found routinely in a periodontitis environment. Comparative studies in the field of periodontal regeneration found better outcomes for exosomes even when compared to their native parent stem cells. In total 47 diagnostic studies revealed a role for salivary/crevicular fluid exosomes for the diagnosis of birth defects, cardiovascular disease, diabetes, gingival recession detection, gingivitis, irritable bowel syndrome, neurodegenerative disease, oral lichen planus, oral squamous cell carcinoma, oropharyngeal cancer detection, orthodontic root resorption, pancreatic cancer, periodontitis, peri-implantitis, Sjögren syndrome, and various systemic diseases. Hence, we characterize the exosomes as possessing "remarkable" potential, serving as a valuable tool for clinicians with significant advantages.

Hyaluronic acid enhances cell migration, viability, and mineralized tissue-specific genes in cementoblasts.

BACKGROUND/OBJECTIVES: It has been repeatedly demonstrated that cementum formation is a crucial step in periodontal regeneration. Hyaluronic acid (HA) is an important component of the extracellular matrix which regulates cells functions and cell-cell communication. Hyaluronic acid/derivatives have been used in regenerative periodontal therapy, but the cellular effects of HA are still unknown. To investigate the effects of HA on cementoblast functions, cell viability, migration, mineralization, differentiation, and mineralized tissue-associated genes and cementoblast-specific markers of the cementoblasts were tested. MATERIALS AND METHODS: Cementoblasts (OCCM-30) were treated with various dilutions (0, 1:2, 1:4, 1:8, 1:16, 1:32, 1:64, 1:128) of HA and examined for cell viability, migration, mineralization, and gene expressions. The mRNA expressions of osteocalcin (OCN), runt-related transcription factor 2 (Runx2), bone sialoprotein (BSP), collagen type I (COL-I), alkaline phosphatase (ALP), cementum protein-1 (CEMP-1), cementum attachment protein (CAP), and small mothers against decapentaplegic (Smad) -1, 2, 3, 6, 7, ß-catenin (Ctnnb1) were performed with real-time polymerase chain reaction (RT-PCR). Total RNA was isolated on days 3 and 8, and cell viability was determined using MTT assay on days 1 and 3. The cell mineralization was evaluated by von Kossa staining on day 8. Cell migration was assessed 2, 4, 6, and 24 hours following exposure to HA dilutions using an in vitro wound healing assay (0, 1:2, 1:4, 1:8). RESULTS: At dilution of 1:2 to 1:128, HA importantly increased cell viability (p < .01). HA at a dilution of 1/2 increased wound healing rates after 4 h compared to the other dilutions and the untreated control group. Increased numbers of mineralized nodules were determined at dilutions of 1:2, 1:4, and 1:8 compared with control group. mRNA expressions of mineralized tissue marker including COL-I, BSP, RunX2, ALP, and OCN significantly improved by HA treatments compared with control group both on 3 days and on 8 days (p < .01). Smad 2, Smad 3, Smad 7, and ß-catenin (Ctnnb1) mRNAs were up-regulated, while Smad1 and Smad 6 were not affected by HA administration. Additionally, HA at dilutions of 1:2, 1:4, and 1:8 remarkably enhanced CEMP-1 and CAP expressions in a dilution- and time-dependent manner (p < .01). CONCLUSIONS: The present results have demonstrated that HA affected the expression of both mineralized tissue markers and cementoblast-specific genes. Positive effects of HA on the cementoblast functions demonstrated that HA application may play a key role in cementum regeneration.

Clinical Evaluation of a Novel Combination of Sodium Hypochlorite/Amino Acid and Cross-linked Hyaluronic Acid Adjunctive to Non-surgical Periodontal Treatment: A Case Series.

PURPOSE: The adjunctive subgingival application of sodium hypochlorite/amino acid and a mixture of natural and cross-linked hyaluronic acid gels (high molecular weight) has been recently proposed as a novel modality to enhance the outcomes of non-surgical periodontal therapy. The aim of this prospective case series was to evaluate the clinical outcomes obtained following the subgingival application of a combination of sodium hypochlorite/amino acid and a mixture of natural and cross-linked hyaluronic acid (high molecular) gels in conjunction with non-surgical periodontal therapy. MATERIAL AND METHODS: Twenty-one systemically healthy, non-smoking patients diagnosed with stage II-III, grade A/B periodontitis underwent full-mouth subgingival debridement (SD) performed with ultrasonic and hand instruments. All sites with probing depths (PD) ≥ 4 mm were treated with additional repeated (i.e., 2-3 times) instillation of sodium hypochlorite/amino acid gel in the periodontal pockets prior to and during SRP. Following mechanical debridement, a mixture of natural and cross-linked hyaluronic acid (high molecular) gel was applied in the pockets. The primary outcome variable was PD reduction; changes in clinical attachment level (CAL) and bleeding on probing (BOP) were the secondary outcomes. The clinical parameters were assessed at baseline, 3 and 6 months after therapy. RESULTS: Compared to baseline, a statistically significant mean reduction of PD values was obtained after 3 and 6 months, amounting to 2.6 ± 0.4 mm, and 2.9 ± 0.4 mm, respectively (p < 0.001). Mean CAL gain measured 2.3 ± 0.5 mm at 3 months and 2.6 ± 0.5 mm at 6 months in comparison to baseline (p < 0.001). Mean reduction of BOP values was 54.9 ± 16.9 % at 3 months and 65.6 ± 16.4 % at 6 months (p < 0.001). The number of moderate pockets (4-5 mm) decreased from 1808 at baseline to 274 at the 6-month evaluation, and the number of deep (≥ 6 mm) pockets dropped from 319 to 3, respectively. CONCLUSION: The combination of sodium hypochlorite/amino acid and a mixture of natural and cross-linked hyaluronic acid (high molecular) adjunctive to subgingival debridement may represent a valuable approach to improve the outcomes of non-surgical periodontal treatment.

Longitudinal assessment of peri-implant diseases in patients with and without history of periodontitis: A 20-year follow-up study.

PURPOSE: To longitudinally assess the prevalence of peri-implant health, peri-implant mucositis and peri-implantitis in a cohort of patients with and without history of periodontitis over a 20-year period. MATERIALS AND METHODS: Eighty-four patients who attended a specialist private periodontal practice were evaluated prospectively 10 and 20 years after prosthesis delivery. Following successful completion of periodontal/implant therapy, patients (172 implants) were enrolled on an individualised supportive periodontal care programme. Clinical and radiographic parameters were collected to assess the prevalence of peri-implant health and diseases. Prevalence of peri-implantitis and peri-implant mucositis was calculated based on the case definition set out in 2018. A multilevel logistic regression analysis was conducted to assess potential risk or protective factors. RESULTS: The analysis was performed on 22 periodontally healthy and 62 periodontally compromised patients rehabilitated with 39 and 130 implants, respectively. The 10-year prevalence of peri-implant health, peri-implant mucositis and peri-implantitis was 21.4%, 67.9% and 10.6%, respectively, whereas the 20-year prevalence was 29.8%, 47.6% and 33.3%, respectively. Non-compliant periodontally compromised patients showed a statistically significantly increased risk at 20 years of both peri-implant mucositis (odds ratio 11.1; 95% confidence interval 1.8-68.6) and peri-implantitis (bone loss and probing depth) (odds ratio 14.3; 95% confidence interval 1.8-32.9). High full-mouth plaque and bleeding scores were associated with higher odds of both peri-implant mucositis and peri-implantitis. CONCLUSIONS: Peri-implant diseases were prevalent in patients rehabilitated with dental implants and followed up for a period of 20 years. History of periodontal disease and a lack of compliance with a tailored supportive periodontal care programme were identified as risk factors for peri-implant diseases.

Mechanical force application and inflammation induce osteoclastogenesis by independent pathways.

OBJECTIVE: To investigate the functional changes of PDL fibroblasts in the presence of mechanical force, inflammation, or a combination of force and inflammation. MATERIALS AND METHODS: Inflammatory supernatants were prepared by inoculating human neutrophils with Porphyromonas gingivalis. Primary human PDL fibroblasts (PDLF), gingival fibroblasts (GFs), and osteoblasts (Saos2) were then exposed to the inflammatory supernatants. Orthodontic force on the PDLFs was simulated by centrifugation. Analyses included cell proliferation, cell viability, cell cycle, and collagen expression, as well as osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-Β ligand (RANKL) expression. RESULTS: Mechanical force did not affect PDLF viability, but it increased the metabolic rate compared to resting cells. Force application shifted the PDLF cell cycle to the G0/G1 phase, arresting cell proliferation and leading to elevated collagen production, mild OPG level elevation, and robust RANKL level elevation. Including an inflammatory supernatant in the presence of force did not affect PDLF viability, proliferation, or cytokine expression. By contrast, the inflammatory supernatant increased RANKL expression in GFs, but not in Saos2 cells. CONCLUSION: Applying mechanical force significantly affects PDLF function. Although inflammation had no effect on PDLF or Saos2 cells, it promoted RANKL expression in GF cells. Within the limitations of the in vitro model, the results suggest that periodontal inflammation and mechanical forces could affect bone catabolism through effects on different cell types, which may culminate in synergistic bone resorption.

Complications and treatment errors related to regenerative periodontal surgery.

Regenerative periodontal surgical procedures are an important component in the treatment of advanced periodontitis. They aim to improve the long-term prognosis of teeth that are periodontally compromised by the presence of intrabony and/or furcation defects, resulting biologically in formation of root cementum, periodontal ligament, and alveolar bone and evidenced clinically by reduction of deep pockets to maintainable probing depths and/or improvements of vertical and horizontal furcation depth. Over the last 25 years, substantial clinical evidence has been accumulated to support the value of regenerative procedures in periodontally compromised dentitions. However, treatment success requires close attention to certain factors on the level of the patient, the tooth/defect, and the operator. Ignoring these factors in case selection, treatment planning, and treatment execution will increase the risk of complications that may jeopardize clinical success and may even be considered as treatment errors. Based on the currently available evidence from clinical practice guidelines, treatment algorithms, and on expert opinion, the present article provides an overview on the main factors, which influence the outcomes of regenerative periodontal surgery and gives recommendations on how to prevent complications and treatment errors.

Histological evaluation following treatment of recession-type defects with coronally advanced flap and a novel human recombinant amelogenin.

OBJECTIVES: To histologically evaluate the effects of a novel human recombinant amelogenin (rAmelX) on periodontal wound healing / regeneration in recession-type defects. MATERIALS AND METHODS: A total of 17 gingival recession-type defects were surgically created in the maxilla of three minipigs. The defects were randomly treated with a coronally advanced flap (CAF) and either rAmelX (test), or a CAF and placebo (control). At three months following reconstructive surgery, the animals were euthanized, and the healing outcomes histologically evaluated. RESULTS: The test group yielded statistically significantly (p = 0.047) greater formation of cementum with inserting collagen fibers compared with the control group (i.e., 4.38 mm ± 0.36 mm vs. 3.48 mm ± 1.13 mm). Bone formation measured 2.15 mm ± 0.8 mm in the test group and 2.24 mm ± 1.23 mm in the control group, respectively, without a statistically significant difference (p = 0.94). CONCLUSIONS: The present data have provided for the first-time evidence for the potential of rAmelX to promote regeneration of periodontal ligament and root cementum in recession-type defects, thus warranting further preclinical and clinical testing. CLINICAL RELEVANCE: The present results set the basis for the potential clinical application of rAmelX in reconstructive periodontal surgery.

Clinical and radiographic outcomes of implant-supported zirconia fixed dental prostheses with cantilever extension: A proof-of-principle study with a follow-up of at least 1 year.

OBJECTIVES: To test the reliability of full zirconia implant-supported fixed dental prostheses with cantilever extension (FDPCs) after at least 1 year of function. MATERIALS AND METHODS: Thirty-five patients in need of implant-supported single unit crowns (SUC) and FDPCs in posterior areas were enrolled. After implant placement, patients were rehabilitated with screw-retained full-zirconia FDPCs. Implant survival rate, pocket probing depth (PPD), presence/absence of bleeding on probing (BoP), and presence/absence of mechanical/technical complications were recorded. Mesial and distal radiographic marginal bone levels (mBLs) from baseline (i.e., recall appointment 3-6 months after implant loading [T0]) to the follow-up examination (i.e., latest recall appointment after at least 12 months after T0 [T1]), were calculated. RESULTS: Thirty patients with 34 FDPCs (31 SUCs and 3 FDPs) supported by 37 implants were available for analysis after a mean loading time of 2.6 ± 1.5 years (range: 13-87 months). No implants were lost. MBLs and mean PPD values did not change statistically significantly from T0 to T1 from 0.92 mm ± 0.42 to 0.96 mm ± 0.38 (95% CI: -0.07/0.17; p = .418) and from 2.99 mm ± 0.70 to 3.27 mm ± 0.71 (95% CI: -0.11/0.68; p = .25) respectively. Peri-implant mucositis was diagnosed in 22 cases. Screw-loosening and zirconia chipping occurred 1× in 4 patients. CONCLUSION: Within the limitations of the present proof-of-principle study, the use of full-zirconia FDPCs in posterior areas seems a valid and safe short-term treatment option.

Defect angle as prognostic indicator in the reconstructive therapy of peri-implantitis.

OBJECTIVE: To analyze the influence of the characteristics of bone defects caused by peri-implantitis on the clinical resolution and radiographic bone gain following reconstructive surgery. METHODS: This is a secondary analysis of a randomized clinical trial. Periapical x-rays of bone defects, caused by peri-implantitis exhibiting intrabony component, were analyzed at baseline and 12-month follow-up after reconstructive surgery. Therapy consisted of anti-infective therapy along with a mixture of allografts with or without a collagen barrier membrane. The association of defect configuration, defect angle (DA), defect width (DW), and baseline marginal bone level (MBL) with clinical resolution (based on a prior defined composite criteria) and radiographic bone gain was correlated by means of generalized estimating equations. RESULTS: Overall, 33 patients with a total of 48 implants exhibiting peri-implantitis were included. None of the evaluated variables yielded statistical significance with disease resolution. Defect configuration demonstrated statistical significance when compared to class 1B and 3B, favoring radiographic bone gain for the former (p = 0.005). DW and MBL did not demonstrate statistical significance with radiographic bone gain. On the contrary, DA exhibited strong statistical significance with bone gain (p < 0.001) in the simple and multiple logistic regression analyses. Mean DA reported in this study was 40°, and this resulted in 1.85 mm radiographic bone gain. To achieve ≥1 mm of bone gain, DA must be <57°, while to attain ≥2 mm of bone gain, DA must be <30°. CONCLUSION: Baseline DA of peri-implantitis intrabony components predicts radiographic bone gain in reconstructive therapy (NCT05282667-this clinical trial was not registered prior to participant recruitment and randomization).

Prevention and treatment of peri-implant diseases-The EFP S3 level clinical practice guideline.

BACKGROUND: The recently published Clinical Practice Guidelines (CPGs) for the treatment of stages I-IV periodontitis provided evidence-based recommendations for treating periodontitis patients, defined according to the 2018 classification. Peri-implant diseases were also re-defined in the 2018 classification. It is well established that both peri-implant mucositis and peri-implantitis are highly prevalent. In addition, peri-implantitis is particularly challenging to manage and is accompanied by significant morbidity. AIM: To develop an S3 level CPG for the prevention and treatment of peri-implant diseases, focusing on the implementation of interdisciplinary approaches required to prevent the development of peri-implant diseases or their recurrence, and to treat/rehabilitate patients with dental implants following the development of peri-implant diseases. MATERIALS AND METHODS: This S3 level CPG was developed by the European Federation of Periodontology, following methodological guidance from the Association of Scientific Medical Societies in Germany and the Grading of Recommendations Assessment, Development and Evaluation process. A rigorous and transparent process included synthesis of relevant research in 13 specifically commissioned systematic reviews, evaluation of the quality and strength of evidence, formulation of specific recommendations, and a structured consensus process involving leading experts and a broad base of stakeholders. RESULTS: The S3 level CPG for the prevention and treatment of peri-implant diseases culminated in the recommendation for implementation of various different interventions before, during and after implant placement/loading. Prevention of peri-implant diseases should commence when dental implants are planned, surgically placed and prosthetically loaded. Once the implants are loaded and in function, a supportive peri-implant care programme should be structured, including periodical assessment of peri-implant tissue health. If peri-implant mucositis or peri-implantitis are detected, appropriate treatments for their management must be rendered. CONCLUSION: The present S3 level CPG informs clinical practice, health systems, policymakers and, indirectly, the public on the available and most effective modalities to maintain healthy peri-implant tissues, and to manage peri-implant diseases, according to the available evidence at the time of publication.

In-Vitro Safety Evaluation of Sodium Hypochlorite (NaOCl) as Part of Step 2 and Maintenance Therapy Protocols in Patients with Periodontitis Stages III-IV.

PURPOSE: Since NaOCl acts as a strong oxidizing agent and presents potential toxicity, this study was adressed to evaluate the in-vitro safety of NaOCl solutions at concentrations below the limit of patient tolerance, i.e. ≥ 0.5%. MATERIALS AND METHODS: First, an in-silico evaluation was conducted to predict the potential toxicity of NaOCl in terms of mutagenic, tumorigenic, irritant, and reproductive risks, as well as some drug-like properties of the molecule. The in-vitro experiments were based on 2D and 3D models. For the 2D approach, two selected cell lines - HaCaT (human skin keratinocytes) and HGF (human gingival fibroblasts) - were exposed to NaOCl at five concentrations (0.05 - 0.5%) for 10, 30, and 60 s to simulate possible clinical administration. The irritative potential of NaOCl 0.05% and 0.25% was assessed in a 3D in-vitro model (EpiDerm, reconstructed human epidermis). Statistical significance was set at p < 0.05. RESULTS: The main findings suggest that NaOCl exerts cytotoxicity towards HaCaT immortalised keratinocytes and HGF primary gingival fibroblasts in a cell type-, dose- and time-dependent manner, with the most prominent effect being recorded in HaCaT cells after 60 s of treatment with NaOCl 0.5%. However, NaOCl was computationally predicted as free of mutagenic, tumorigenic, irritant, and reproductive toxicity, and showed no irritative potential in 3D reconstructed epidermis at concentrations of 0.05% and 0.25%. CONCLUSION: Further clinical and histological studies are required to confirm these results, as well as elucidate the potential cytotoxic mechanism induced by NaOCl in HaCaT and HGF cells at the tested concentrations.

Healing of intrabony defects using a novel human recombinant amelogenin: a preclinical study.

OBJECTIVE: To histologically evaluate the effects of a novel human recombinant amelogenin (rAmelX) on periodontal wound healing/regeneration in intrabony defects. METHOD AND MATERIALS: Intrabony defects were surgically created in the mandible of three minipigs. Twelve defects were randomly treated with either rAmelX and carrier (test group) or with the carrier only (control group). At 3 months following reconstructive surgery, the animals were euthanized, and the tissues histologically processed. Thereafter, descriptive histology, histometry, and statistical analyses were performed. RESULTS: Postoperative clinical healing was uneventful. At the defect level, no adverse reactions (eg, suppuration, abscess formation, unusual inflammatory reaction) were observed with a good biocompatibility of the tested products. The test group yielded higher values for new cementum formation (4.81 ± 1.17 mm) compared to the control group (4.39 ± 1.71 mm) without reaching statistical significance (P = .937). Moreover, regrowth of new bone was greater in the test compared to the control group (3.51 mm and 2.97 mm, respectively, P = .309). CONCLUSIONS: The present results provided for the first-time histologic evidence for periodontal regeneration following the use of rAmelX in intrabony defects, thus pointing to the potential of this novel recombinant amelogenin as a possible alternative to regenerative materials from animal origins.

Resolution of peri-implant mucositis at tissue- and bone-level implants: A 6-month prospective controlled clinical trial.

OBJECTIVE: The objective of the study was to compare resolution of inflammation of naturally occurring peri-implant mucositis (PM) at tissue-level (TL) and bone-level (BL) implants after non-surgical mechanical debridement. MATERIALS AND METHODS: Fifty-four patients with 74 Implants with PM were allocated in two groups (39 TL and 35 BL implants) and treated by means of subgingival debridement using a sonic scaler with a plastic tip without adjunctive measures. At baseline and at 1, 3, 6 months, the full-mouth plaque score (FMPS), full-mouth bleeding score (FMBS), probing depth (PD), bleeding on probing (BOP), and modified plaque index (mPlI) were recorded. The primary outcome was BOP change. RESULTS: After 6 months, the FMPS, FMBS, PD, and number of implants with plaque decreased statistically significantly in each group (p < .05); however, no statistically significant differences were found between TL and BL implants (p > .05). After 6 months, 17 (43.6%) TL and 14 (40%) BL implants showed a BOP change in (17.9%) and (11.4%), respectively. No statistical difference was recorded between groups. CONCLUSIONS: Within the limitations of present study, the findings showed no statistically significant differences in terms of changes in clinical parameters following non-surgical mechanical treatment of PM at TL and BL implants. A complete resolution of PM (i.e., no BOP at all implant sites) was not achieved in both groups.

Effect of argon plasma pre-treatment of healing abutments on peri-implant microbiome and soft tissue integration: a proof-of-concept randomized study.

PURPOSE: Biofilm-free implant surface is ultimate prerequisite for successful soft and bone tissue integration. Objective of the study was to estimate the effects of argon plasma healing abutment pre-treatment (PT) on peri-implant soft-tissue phenotype (PiSP), inflammation, plaque accumulation and the microbiome (PiM) between non-treated (NPT) and treated (PT) abutments following 3-months healing period. The hypothesis was that cell-conductive and antimicrobial properties of PT would yield optimal conditions for soft tissue integration. MATERIAL AND METHODS: Two months following second-phase surgery, microbiological and clinical parameters were assessed around thirty-six healing abutments with two types of microtopography, smooth surface (MACHINED) and ultrathin threaded microsurface (ROUGH). A two level randomization schema was used to achieve equal distribution and abutments were randomly divided into rough and machined groups, and then divided into PT and NPT groups. PiM was assessed using next-generation DNA sequencing. RESULTS: PiM bacterial composition was highly diverse already two months post-implantation, consisting of key-stone pathogens, early and late colonizers, while the mycobiome was less diverse. PT was associated with lower plaque accumulation and inflammation without significant impact on PiSP, while in NPT clinical parameters were increased and associated with periopathogens. NPT mostly harbored late colonizers, while PT exerted higher abundance of early colonizers suggesting less advanced plaque formation. Interaction analysis in PT demonstrated S. mitis co-occurrence with pro-healthy Rothia dentocariosa and co-exclusion with Parvimonas micra, Porphyromonas endodontalis and Prevotella oris. PiSP parameters were generally similar between the groups, but significant association between PiM and keratinized mucosa width was observed in both groups, with remarkably more expressed diversity in NPT compared to PT. PT resulted in significantly lower BOP and PI around rough and machined abutments, respectively, without specific effect on PiM and PiSP. CONCLUSIONS: PT contributed to significantly the less advanced biofilm accumulation and inflammation without specific effects on PiSP.

Physiopathology of peri-implant diseases.

BACKGROUND: Peri-implant health is characterized by the absence of clinical signs of soft tissue inflammation. Peri-implant diseases are initiated by the presence of bacterial biofilms and share a similar etiology as that involved in the onset of periodontal diseases. PURPOSE: To summarize available evidence on the physiopathology of peri-implant diseases with emphasis on similarities and differences with periodontal diseases. MATERIALS AND METHODS: Evidence on the biologic mechanisms involved in the pathogenesis of peri-implant mucositis and peri-implantitis were explored in the recent scientific literature. RESULTS: Findings of studies in animals and in humans indicate that experimental peri-implant mucositis leads to a larger inflammatory connective tissue infiltrate and to a higher frequency of bleeding sites around implants compared with teeth. Tissue destruction at experimental peri-implantitis sites is more pronounced compared with that at experimental periodontitis sites. Although human periodontitis and peri-implantitis lesions share similarities with respect to etiology and clinical features, they represent distinct entities from a physiopathologic point of view. CONCLUSIONS: Diagnosis of peri-implant health requires a clinical examination to confirm absence of peri-implant soft tissue inflammation. In order to make a correct diagnosis and select the appropriate therapeutic steps to manage peri-implant diseases, knowledge of their pathogenetic mechanisms is required.