Correction: Vicencio et al. Transcriptional Signatures and Network-Based Approaches Identified Master Regulators Transcription Factors Involved in Experimental Periodontitis Pathogenesis. Int. J. Mol. Sci. 2023, 24, 14835.

In the original publication [...].

Transcriptional Signatures and Network-Based Approaches Identified Master Regulators Transcription Factors Involved in Experimental Periodontitis Pathogenesis.

Periodontitis is a chronic inflammatory disease characterized by the progressive and irreversible destruction of the periodontium. Its aetiopathogenesis lies in the constant challenge of the dysbiotic biofilm, which triggers a deregulated immune response responsible for the disease phenotype. Although the molecular mechanisms underlying periodontitis have been extensively studied, the regulatory mechanisms at the transcriptional level remain unclear. To generate transcriptomic data, we performed RNA shotgun sequencing of the oral mucosa of periodontitis-affected mice. Since genes are not expressed in isolation during pathological processes, we disclose here the complete repertoire of differentially expressed genes (DEG) and co-expressed modules to build Gene Regulatory Networks (GRNs) and identify the Master Transcriptional Regulators of periodontitis. The transcriptional changes revealed 366 protein-coding genes and 42 non-coding genes differentially expressed and enriched in the immune response. Furthermore, we found 13 co-expression modules with different representation degrees and gene expression levels. Our GRN comprises genes from 12 gene clusters, 166 nodes, of which 33 encode Transcription Factors, and 201 connections. Finally, using these strategies, 26 master regulators of periodontitis were identified. In conclusion, combining the transcriptomic analyses with the regulatory network construction represents a powerful and efficient strategy for identifying potential periodontitis-therapeutic targets.

Preclinical Evidence for the Use of Oral Mesenchymal Stem Cell-Derived Extracellular Vesicles in Bone Regenerative Therapy: A Systematic Review.

The development of extracellular vesicles (EVs) therapies has revolutionized personalized medicine, opening up new possibilities for treatment. EVs have emerged as a promising therapeutic tool within this field due to their crucial role in intercellular communication across various cell types and organisms. This systematic review aims to evaluate the therapeutic potential of oral mesenchymal stem cell (MSC)-derived EVs for bone regeneration, specifically focusing on findings from preclinical models. Sixteen articles meeting the inclusion criteria were selected following document analysis. The biological effects of oral MSC-derived EVs predominantly involve the upregulation of proteins associated with angiogenesis, and inflammation resolution, alongside the downregulation of proinflammatory cytokines. Moreover, these therapeutic agents have been found to contain a significant quantity of different molecules (proteins, lipids, DNA, microRNAs, etc) further contributing to their modulatory potential. The findings from this systematic review underscore that oral MSC-derived EVs, irrespective of their specific population, have the ability to enhance the osteogenic repair response in maxillary bone or periodontal defects. In summary, this systematic review highlights the promising potential of oral MSC-derived EVs for bone regeneration based on evidence from preclinical models. The comprehensive assessment of their biological effects and the presence of microRNAs underscores their therapeutic significance. These findings support the utilization of oral MSC-derived EVs in enhancing the osteogenic repair response in various maxillary bone or periodontal defects, providing insights into the mechanisms involved and potential therapeutic applications in the field of personalized medicine.

Clinical efficacy of guided bone regeneration in peri-implantitis defects. A network meta-analysis.

Guided bone regeneration (GBR) at peri-implantitis-related bone defects involves the placement of bone-filler particles in the intrabony defects and the application of a barrier membrane. The efficacy of different GBR-supported reconstructive measures as well as their potential superiority compared to non-GBR-supported treatment strategies for bone defects at peri-implantitis sites, however, remains unclear. Therefore, this analysis was designed to evaluate the long-term (≥12 months) clinical efficacy of GBR-supported reconstructive surgical therapy for peri-implantitis-related bone defects. In terms of resolving inflammation, the implementation of GBR protocols applying xenogenic bone substitutes yielded a higher reduction of bleeding on probing and probing depth value compared to the GBR protocol applying autogenous bone. Furthermore, for the changes in bleeding on probing and probing depths, GBR approaches using xenogenic bone showed superiority over the non-GBR treatments. Xenogenic bone with or without a barrier membrane was associated with improved radiographic bone levels and less soft tissue recession compared to the use of a GBR protocol implementing autogenous bone. Nonetheless, when interpreting this findings, the limited number of available studies with low to serious risk of bias and the short follow-up periods limited to 12 months should be considered.

Levels of Pro-Inflammatory and Bone-Resorptive Mediators in Periodontally Compromised Patients under Orthodontic Treatment Involving Intermittent Forces of Low Intensities.

During orthodontic treatment, diverse cytokines, enzymes, and osteolytic mediators produced within the teeth surrounding periodontal tissues determine the rate of alveolar bone remodeling and consequent teeth movement. In patients with teeth presenting reduced periodontal support, periodontal stability should be ensured during orthodontic treatment. Thus, therapies based on the application of low-intensity intermittent orthodontic forces are recommended. To determine if this kind of treatment is periodontally well tolerated, this study aimed to analyze the production of receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), interleukin (IL)-6, IL-17A, and matrix metalloproteinase (MMP)-8 in periodontal tissues of protruded anterior teeth with reduced periodontal support and undergoing orthodontic treatment. Patients with periodontitis-associated anterior teeth migration received non-surgical periodontal therapy and a specific orthodontic treatment involving controlled low-intensity intermittent orthodontic forces. Samples were collected before periodontitis treatment, after periodontitis treatment, and at 1 week to 24 months of the orthodontic treatment. During the 2 years of orthodontic treatment, no significant differences were detected in the probing depth, clinical attachment level, supragingival bacterial plaque, and bleeding on probing. In line with this, the gingival crevicular levels of RANKL, OPG, IL-6, IL-17A, and MMP-8 did not vary between the different evaluation time-points of the orthodontic treatment. When compared with the levels detected during the periodontitis, the RANKL/OPG ratio was significantly lower at all the analyzed time-points of the orthodontic treatment. In conclusion, the patient-specific orthodontic treatment based on intermittent orthodontic forces of low intensities was well tolerated by periodontally compromised teeth with pathological migration.

Periodontal bacteria in the brain-Implication for Alzheimer's disease: A systematic review.

Periodontitis is a chronic non-communicable disease caused by a dysbiotic microbiota. Pathogens can spread to the bloodstream, colonize other tissues or organs, and favor the onset of other pathologies, such as Alzheimer's disease (AD). Pathogens could permanently or transiently colonize the brain and induce an immune response. Thus, we analyzed the evidence combining oral bacteria's detection in the brain, both in animals and humans affected with AD. This systematic review was carried out following the PRISMA guideline. Studies that detected oral bacteria at the brain level were selected. The search was carried out in the Medline, Latindex, SciELO, and Cochrane Library databases. SYRCLE tool and Newcastle-Ottawa Scale were used for the risk of bias assessment. 23 studies were selected according to the eligibility criteria. Infection with oral pathogens in animals was related to developing neuropathological characteristics of AD and bacteria detection in the brain. In patients with AD, oral bacteria were detected in brain tissues, and increased levels of pro-inflammatory cytokines were also detected. There is evidence of a microbiological susceptibility to develop AD when the most dysbiosis-associated oral bacteria are present. The presence of bacteria in the brain is related to AD's pathological characteristics, suggesting an etiological oral-brain axis.

Esthetic and clinical outcomes after immediate placement and restoration: Comparison of two implant systems in the anterior maxilla-A cross-sectional study.

AIM: To assess the esthetic and clinical performance of a novel self-tapping implant system for single-tooth restorations in the esthetic zone after immediate placement and provisionalization. MATERIALS AND METHODS: This cross-sectional study included 52 patients contributing a total of 52 immediately placed and restored implants with ≥12 months after functional loading, comparing two different implant systems: Straumann® BLX (Institut Straumann AG, Basel, Switzerland; 25 patients) and Ankylos® (Dentsply Sirona, Hanau, Germany; 27 patients). As the primary outcome measure, peri-implant tissue esthetics were assessed by means of pink esthetics score (PES) rated by three independent clinicians. Moreover, as secondary outcome measures, the peri-implant tissue health was assessed by means of bleeding on probing, probing depth, and suppuration. Apart from that, the modified plaque index, keratinized mucosa width, and the presence of mucosal recessions were also assessed. When clinical signs suggested the possibility of peri-implantitis, radiographs were indicated to assess progressive bone loss. RESULTS: The mean PES ratings were 12.10 ± 1.10 for Ankylos versus 11.2 ± 1.86 for BLX, both achieving good esthetic results without significant differences (p = 0.143). There were no differences among most clinical parameters (plaque, bleeding on probing, probing depth, peri-implant mucosal recession), although peri-implant mucositis was present in one-third of the cases. The inter-rater agreement on esthetics was not significant (p < 0.250). CONCLUSION: Within the limitations of the present study, it was concluded that the use of either BLX or Ankylos implant systems was associated to comparable peri-implant health and good pink esthetic outcomes during immediate implantation and restoration protocols, for at least 12 months.

Surgical interventions for the treatment of peri-implantitis.

BACKGROUND: Peri-implantitis constitutes one of the most frequent late dental implant complications. The disease is initiated by bacterial infection; therefore, anti-infective peri-implantitis treatment strategies are required to arrest the progressive marginal bone loss and maintain the affected implant in function. Although nonsurgical treatment strategies appear to be of limited predictability, treatment outcomes have been frequently improved following surgical interventions. PURPOSE: The present narrative review describes various surgical peri-implantitis treatment modalities, with respect to their indications, performance, and effectiveness. MATERIALS AND METHODS: The present narrative review considered the most relevant studies in the field published in the English language. RESULTS: Surgical peri-implantitis treatment approaches can be categorized as nonreconstrucive therapy, reconstructive therapy, and combined therapy (ie, reconstructive and resective therapy). In addition to disease resolution, reconstructive approaches also seek to regenerate the bone defect and achieve reosseointegration. CONCLUSIONS: The severity of the disease, the regenerative potential of the defetc and esthetic demands of the patient are the factors determining the surgical peri-implantitis treatment modality.

Electrolyzed water for the microbiologic control in the pandemic dental setting: a systematic review.

BACKGROUND: Electrolyzed water has brought recent attention due to its antimicrobial properties. Indeed, electrolyzed water has been proposed to sterilize dental materials and instruments without compromising their structural integrity. In addition, electrolyzed water has been proposed as a mouthwash to control bacterial and viral oral infections without detrimental effects on the oral mucosa. However, no current consensus or evidence synthesis could indicate its potentially favorable use in the dental setting, particularly during the COVID-19 context. Therefore, this systematic review aimed to elucidate whether electrolyzed water could improve microbiologic control in the COVID-19 pandemic dental setting. METHODS: MEDLINE via Pubmed, EMBASE, Cochrane's CENTRAL, Scopus, LILACS, and Web of Science databases were searched up to September 2021 to identify experimental studies utilizing electrolyzed water for eliminating microorganisms in a dental setting. Besides, a manual and a grey literature search were performed. The data selection and extraction were performed individually and in duplicate. The Risk of Bias (RoB) was assessed with the Nature Publication Quality Improvement Project (NPQIP) score sheet. The study protocol was registered at PROSPERO CRD42020206986. RESULTS: From a total of 299 articles, 63 studies met the inclusion criteria. The included studies assessed several types of electrolyzed waters, which showed a high disinfection potential when used to deal with different oral conditions. Electrolyzed water demonstrated a broad antimicrobial spectrum and was highly efficient in the dental office disinfection against viruses, fungi, and bacteria, being compatible with most dental materials. In addition, electrolyzed water could protect against SARS-CoV-2 infection and contamination in the dental office. Regarding the RoB, only 35.18% of entries were answered as 'Yes', thus achieving less than half of the reporting sheet. CONCLUSION: Electrolyzed water effectively disinfects contaminated surfaces, dental materials, and equipment. Therefore, their use is recommendable in the SARS-CoV-2 pandemic dental setting.

Immediate versus delayed implant placement in the esthetic zone: a prospective 3D volumetric assessment of peri-implant tissue stability.

PURPOSE: To evaluate the volumetric stability of peri-implant soft and hard tissue prospectively, this study compared immediate versus delayed implants placed in the anterior esthetic region. METHODS: This non-randomized controlled clinical study included 25 patients, who received an immediate (type 1) or a delayed (type 4) implant placement for the replacement of a single anterior tooth. The anterior maxillae were intraorally scanned at three timepoints: before surgery (S0), 6 months (S1), and 12 months (S2) after surgery. A specific region of interest (ROI), divided into marginal and apical regions, was determined and superimposed for volumetric changes analysis. At 6 and 12 months, the probing depth (PD), bleeding/suppuration on probing (BOP/SUP), modified plaque index (PI), keratinized mucosa (KM) width, mucosal recession (MR), and implant stability (PTV) by means of periotest were recorded. RESULTS: Between S0-S2, tissue surrounding immediate implants was reduced in 0.37 ± 0.31 mm, whereas delayed implants gained 0.84 ± 0.57 mm mean tissue volume. Peri-implant tissue loss at type 1 implants occurred primarily in the marginal section of the ROI (0.42 ± 0.31 mm), whereas tissue gain at type 4 implants occurred mainly in the apical section (0.83 ± 0.51 mm). These values were significantly different between both groups for the entire ROI (p = 0.0452) and the marginal region (p = 0.0274). In addition, the mean buccal KM width around type 1 implants was significantly wider in comparison with the type 4 implants group after 12 months (p = 0.046). There were no significant differences between groups regarding PD, BOP/SUP, or PTV. CONCLUSIONS: The results suggest that type 1 implants placed in the esthetic region experience more tissue loss than type 4 implants, thus marginal tissue remodeling should be considered for planning immediate implants placement in the anterior maxillae.

Survival and Mechanical Complications of Posterior Single Implant-Supported Restorations Using Prefabricated Titanium Abutments: A Medium- and Long-Term Retrospective Analysis with up to 10 Years Follow-up.

PURPOSE: To evaluate the survival of implants and abutments and the incidence of mechanical complications of single posterior implant-supported restorations using prefabricated titanium abutments. MATERIALS AND METHODS: This retrospective clinical study analyzed 172 Astra Tech OsseoSpeed internal hexagon implants (Dentsply Sirona) placed in 85 patients with a follow-up between January 2009 and January 2019. All implants were restored with prefabricated titanium abutments and cement-retained metal-ceramic crowns. The clinical outcomes recorded were implant and abutment survival rates and mechanical complications (abutment/implant fractures, screw loosening/fracture, decementation of the superstructure, veneer chipping/fractures) and were analyzed according to age, sex, implant length/diameter, bone graft, arch, implant position, parafunctional habit or dental status, and opposite arch. Kaplan-Meier survival analysis was used to determine whether the distribution of time to event/failure differed based on implant position (premolar or molar), implant diameter, or abutment angulation. RESULTS: During the observation period (mean: 108 months), implant and abutment cumulative survival rates were 97.7% and 98.3%, respectively, with no statistically significant differences between implant positions (molar/premolar), implant diameters (3.5 vs 4 mm), or abutment angles (straight vs 15 degrees). Of the 172 single posterior implant-supported restorations, 14 mechanical complications (8.2%) were recorded. In particular, 3 abutment fractures (1.7%), 2 screw loosenings (1.2%), 2 screw fractures (1.2%), 1 implant fracture (0.6%), 2 chipping/fractures of veneering materials (1.2%), and 4 decementations of the superstructure (2.3%) occurred. CONCLUSION: The single posterior implant-supported restorations using prefabricated titanium abutments remain a clinically acceptable treatment in terms of prosthetic procedure and cost-effectiveness.

Senescent CD4+CD28- T Lymphocytes as a Potential Driver of Th17/Treg Imbalance and Alveolar Bone Resorption during Periodontitis.

Senescent cells express a senescence-associated secretory phenotype (SASP) with a pro-inflammatory bias, which contributes to the chronicity of inflammation. During chronic inflammatory diseases, infiltrating CD4+ T lymphocytes can undergo cellular senescence and arrest the surface expression of CD28, have a response biased towards T-helper type-17 (Th17) of immunity, and show a remarkable ability to induce osteoclastogenesis. As a cellular counterpart, T regulatory lymphocytes (Tregs) can also undergo cellular senescence, and CD28- Tregs are able to express an SASP secretome, thus severely altering their immunosuppressive capacities. During periodontitis, the persistent microbial challenge and chronic inflammation favor the induction of cellular senescence. Therefore, senescence of Th17 and Treg lymphocytes could contribute to Th17/Treg imbalance and favor the tooth-supporting alveolar bone loss characteristic of the disease. In the present review, we describe the concept of cellular senescence; particularly, the one produced during chronic inflammation and persistent microbial antigen challenge. In addition, we detail the different markers used to identify senescent cells, proposing those specific to senescent T lymphocytes that can be used for periodontal research purposes. Finally, we discuss the existing literature that allows us to suggest the potential pathogenic role of senescent CD4+CD28- T lymphocytes in periodontitis.

A micro-CT analysis of radicular dentine thickness in mandibular first premolars presenting C-shaped root canals: Identification of potential danger zones.

AIM: To describe the radicular dentine thickness in mandibular first premolars presenting C-shaped root canals, to identify the canal walls with less thickness as potential danger zones. In addition, to describe the internal and external anatomical characteristics of these teeth and associate them with the dentine thickness. METHODOLOGY: A total of 70 mandibular first premolars presenting C-shaped root canals were examined. Their internal morphology was analysed using Vertucci's and Fan's criteria, and their external morphology was analysed using the ASUDAS score. Besides, the dentine thickness around the root canals was two/three-dimensionally determined at five root planes and quantified in the distal and the mesial aspects. RESULTS: According to Fan's, ASUDAS, and Vertucci's classifications, the most common canal configurations were category C3, grade 3, and type V, respectively. In Vertucci's type III anatomy, the mesial root wall of the lingual canal showed significantly less dentine thickness than the distal wall in the middle plane (p = .031). Similarly, in Vertucci's type V anatomy, significantly less dentine thickness was observed in the mesial root wall of the buccal and lingual canals in the middle plane (p < .001) and the buccal canal in the middle-apical plane (p = .014) than the distal root wall of these canals. In teeth with ASUDAS grade 3 and 4 scores, significantly less dentine thickness was observed in the mesial in comparison with the distal root wall of these canals. These differences were demonstrated in the middle and middle-apical planes (p < .001) of grade 3 teeth and the middle-apical plane (p < .001) of grade 4 teeth. In these root planes, the Ver1-AS3 and VerV-AS3 combinations presented a 4-times greater risk of presenting walls with a critical dentine thickness of 0.6 mm (odds ratio [OR] = 4, p = .025) than the combinations Ver1-AS2, VerV-AS2, VerV-AS4, and VerIII-AS3. CONCLUSIONS: The root canal system configuration of mandibular first premolars with C-shaped canals showed a wide range of anatomical variations. The lowest dentine thickness was located in the mesial wall of the canals in the middle and apical root thirds of Vertucci's type III and V anatomies and in teeth with deep radicular grooves scored as ASUDAS grades 3 and 4. In the middle and middle-apical planes, the presence of the combinations Ver1-AS3 and VerV-AS3 showed a high risk of presenting a critical dentine thickness of 0.6 mm. Therefore, these root canal walls with less dentine thickness represent potential instrumentation danger zones in mandibular first premolars with C-shaped canals.

Treatment of a single gingival recession with a subepithelial connective tissue graft with a double papilla flap: A case report.

Gingival recessions are widely prevalent deformities that affect the normal position of the gingiva and cause exposure of the tooth root, and are often associated with unsatisfactory aesthetics and dentin hypersensitivity. The double papilla technique for root covering is a periodontal plastic surgery technique recommended for the treatment of gingival recessions. In this case report, we show the clinical results after a 12-month follow-up of a root-covering procedure in an upper canine affected by a gingival recession. A 56-year-old patient presenting a Cairo type I gingival recession on the vestibular surface of tooth 23 was treated with a one-stage surgical procedure, carried out using the double papilla technique in combination with a partially epithelialized connective tissue graft, reaching 100% root coverage. After a 12-month follow-up, this technique showed highly successful results both in 100% coverage of the defect and in long-term stability and aesthetics.

Natural Killer T (NKT) Cells and Periodontitis: Potential Regulatory Role of NKT10 Cells.

Natural killer T (NKT) cells constitute a unique subset of T lymphocytes characterized by specifically interacting with antigenic glycolipids conjugated to the CD1d receptor on antigen-presenting cells. Functionally, NKT cells are capable of performing either effector or suppressor immune responses, depending on their production of proinflammatory or anti-inflammatory cytokines, respectively. Effector NKT cells are subdivided into three subsets, termed NKT1, NKT2, and NKT17, based on the cytokines they produce and their similarity to the cytokine profile produced by Th1, Th2, and Th17 lymphocytes, respectively. Recently, a new subgroup of NKT cells termed NKT10 has been described, which cooperates and interacts with other immune cells to promote immunoregulatory responses. Although the tissue-specific functions of NKT cells have not been fully elucidated, their activity has been associated with the pathogenesis of different inflammatory diseases with immunopathogenic similarities to periodontitis, including osteolytic pathologies such as rheumatoid arthritis and osteoporosis. In the present review, we revise and discuss the pathogenic characteristics of NKT cells in these diseases and their role in the pathogenesis of periodontitis; particularly, we analyze the potential regulatory role of the IL-10-producing NKT10 cells.

Premature Senescence of T-cells Favors Bone Loss During Osteolytic Diseases. A New Concern in the Osteoimmunology Arena.

Cellular senescence is a biological process triggered in response to time-accumulated DNA damage, which prioritizes cell survival over cell function. Particularly, senescent T lymphocytes can be generated prematurely during chronic inflammatory diseases regardless of chronological aging. These senescent T lymphocytes are characterized by the loss of CD28 expression, a co-stimulatory receptor that mediates antigen presentation and effective T-cell activation. An increased number of premature senescent CD4+CD28- T lymphocytes has been frequently observed in osteolytic diseases, including rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, osteopenia, osteoporosis, and osteomyelitis. Indeed, CD4+CD28- T lymphocytes produce higher levels of osteoclastogenic molecular mediators directly related to pathologic bone loss, such as tumor necrosis factor (TNF)-α, interleukin (IL)-17A, and receptor-activator of nuclear factor κB ligand (RANKL), as compared with regular CD4+CD28+ T lymphocytes. In addition, premature senescent CD8+CD28- T lymphocytes have been negatively associated with bone healing and regeneration by inhibiting osteoblast differentiation and mesenchymal stromal cell survival. Therefore, accumulated evidence supports the role of senescent T lymphocytes in osteoimmunology. Moreover, premature senescence of T-cells seems to be associated with the functional imbalance between the osteolytic T-helper type-17 (Th17) and bone protective T regulatory (Treg) lymphocytes, as well as the phenotypic instability of Treg lymphocytes responsible for its trans-differentiation into RANKL-producing exFoxp3Th17 cells, a key cellular phenomenon directly related to bone loss. Herein, we present a framework for the understanding of the pathogenic characteristics of T lymphocytes with a premature senescent phenotype; and particularly, we revise and discuss their role in the osteoimmunology of osteolytic diseases.

Humanized Mouse Models for the Study of Periodontitis: An Opportunity to Elucidate Unresolved Aspects of Its Immunopathogenesis and Analyze New Immunotherapeutic Strategies.

Periodontitis is an oral inflammatory disease in which the polymicrobial synergy and dysbiosis of the subgingival microbiota trigger a deregulated host immune response, that leads to the breakdown of tooth-supporting tissues and finally tooth loss. Periodontitis is characterized by the increased pathogenic activity of T helper type 17 (Th17) lymphocytes and defective immunoregulation mediated by phenotypically unstable T regulatory (Treg), lymphocytes, incapable of resolving the bone-resorbing inflammatory milieu. In this context, the complexity of the immune response orchestrated against the microbial challenge during periodontitis has made the study of its pathogenesis and therapy difficult and limited. Indeed, the ethical limitations that accompany human studies can lead to an insufficient etiopathogenic understanding of the disease and consequently, biased treatment decision-making. Alternatively, animal models allow us to manage these difficulties and give us the opportunity to partially emulate the etiopathogenesis of periodontitis by inoculating periodontopathogenic bacteria or by placing bacteria-accumulating ligatures around the teeth; however, these models still have limited translational application in humans. Accordingly, humanized animal models are able to emulate human-like complex networks of immune responses by engrafting human cells or tissues into specific strains of immunodeficient mice. Their characteristics enable a viable time window for the study of the establishment of a specific human immune response pattern in an in vivo setting and could be exploited for a wider study of the etiopathogenesis and/or treatment of periodontitis. For instance, the antigen-specific response of human dendritic cells against the periodontopathogen Porphyromonas gingivalis favoring the Th17/Treg response has already been tested in humanized mice models. Hypothetically, the proper emulation of periodontal dysbiosis in a humanized animal could give insights into the subtle molecular characteristics of a human-like local and systemic immune response during periodontitis and support the design of novel immunotherapeutic strategies. Therefore, the aims of this review are: To elucidate how the microbiota-elicited immunopathogenesis of periodontitis can be potentially emulated in humanized mouse models, to highlight their advantages and limitations in comparison with the already available experimental periodontitis non-humanized animal models, and to discuss the potential translational application of using these models for periodontitis immunotherapeutics.

The influence of flap design on patients' experiencing pain, swelling, and trismus after mandibular third molar surgery: a scoping systematic review.

Third molar removal surgery usually comes accompanied by postoperative discomfort, which could be influenced by the surgical approach chosen. This scoping systematic review aimed at compiling the available evidence focused on the influence of flap design, including envelope flap (EF), triangular flap (TF), and modified triangular flap (MTF), on postoperative pain, swelling, and trismus, as primary outcome measures, and any result mentioning healing promotion or delay, as secondary outcome measure, after mandibular third molar extraction surgery. An electronic search, complemented by a manual search, of articles published from 1999 to 2020 was conducted in the Medline (PubMed), EMBASE and Web of Science databases including human randomized controlled trials, prospective, and retrospective studies with at least 15 patients. The risk of bias of the included studies was assessed either with the Cochrane's Risk of Bias tool or with the Newcastle-Ottawa scale. Every step of the review was performed independently and in duplicate. The initial electronic search recovered 2102 articles. After applying the inclusion criteria, 12 articles were included. For patient's perceived postoperative pain, TF and MTF frequently reported better results than EF. For swelling, the literature is divided, despite a trend favoring EF. For trismus, data showed that its occurrence is mostly associated with the duration of the surgery rather than with the chosen flap. For healing, the limited data is inconclusive. Finally, randomized studies showed a high risk of bias, whereas nonrandomized studies were mostly of good quality and low risk of bias. Although there was no clear consensus regarding the influence of different flap designs for third mandibular molar extraction on postoperative clinical morbidities; the surgeon's experience, estimated surgical difficulty, molar position and orientation, and surg ery duration should be considered when choosing among the different flap designs.

Patient satisfaction and survival of maxillary overdentures supported by four or six splinted implants: a systematic review with meta-analysis.

BACKGROUND: Implant-supported overdentures offer enhanced mechanical properties, which lead to better patient satisfaction and survival rates than conventional dentures. However, it is unclear whether these satisfaction levels and survival rates depend on the number of implants supporting the overdenture. Therefore, this systematic review aimed to compare maxillary overdentures supported by four or six splinted implants in terms of patient satisfaction, implant survival, overdenture survival, and prosthodontic complications. METHODS: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (PubMed), and EMBASE databases were systematically searched and complemented by hand searching from 2000 to 2019, employing a combination of specific keywords. Studies comparing the use of four versus six implants for supporting overdentures with at least one-year of follow-up after prosthesis installation and including ten fully edentulous patients were included. The risk of bias (RoB) was analyzed with Cochrane's RoB 2 and Newcastle-Ottawa tools. Implants and prosthesis survival rates were analyzed by random-effects meta-analysis and expressed as risk ratios or risk differences, respectively, and by the non-parametric unpaired Fisher's test. RESULTS: A total of 15 from 1865 articles were included, and reported follow-up times after implant placement ranged from 1 to 10 years. Irrespective of the number of implants used, high scores were reported by all studies investigating patient satisfaction. Meta-analysis and non-parametric Fisher's test showed no statistical differences regarding the survival rate of implants (P = 0.34, P = 0.3) or overdentures (P = 0.74, P = 0.9) when using 4 versus 6 splinted implants to support overdentures, and no significant differences regarding prosthodontic complications were found between groups. Randomized studies presented high RoB and non-randomized studies presented acceptable quality. CONCLUSIONS: Within the limits of this systematic review, we can conclude that the bar-supported overdenture on four implants is not inferior to the overdenture supported by six implants for rehabilitating the edentulous maxilla, in terms of patient satisfaction, survival rates of implants and overdentures, and prosthodontic complications.

Levels of low-molecular-weight hyaluronan in periodontitis-treated patients and its immunostimulatory effects on CD4+ T lymphocytes.

OBJECTIVES: During periodontitis, chronic inflammation triggers soft tissue breakdown, and hyaluronan is degraded into fragments of low molecular weight (LMW-HA). This investigation aimed to elucidate whether LMW-HA fragments with immunogenic potential on T lymphocytes remain in periodontal tissues after periodontal treatment. MATERIALS AND METHODS: GCF samples were obtained from 15 periodontitis-affected patients and the LMW-HA, RANKL, and OPG levels were analyzed before and after 6 months of periodontal treatment by ELISA. Eight healthy individuals were analyzed as controls. Besides, human T lymphocytes were purified, exposed to infected dendritic cells, and pulsed with LMW-HA. Non-treated T lymphocytes were used as control. The expression levels of the transcription factors and cytokines that determine the Th1, Th17, and Th22 lymphocyte differentiation and function were analyzed by RT-qPCR. Similarly, the expression levels of RANKL and CD44 were analyzed. RESULTS: In the GCF samples of periodontitis-affected patients, higher levels of LMW-HA were detected when compared with those of healthy individuals (52.1 ± 15.4 vs. 21.4 ± 12.2, p < 0.001), and these increased levels did not decrease after periodontal therapy (52.1 ± 15.4 vs. 45.7 ± 15.9, p = 0.158). Similarly, the RANKL levels and RANKL/OPG ratios did not change after periodontal therapy. Furthermore, in human T lymphocytes, LMW-HA induced higher expression levels of the Th1, Th17, and Th22-related transcription factors and cytokines, as well as CD44 and RANKL, as compared with non-treated cells. CONCLUSIONS: In some patients, increased levels of LMW-HA persist in periodontal tissues after conventional periodontal therapy, and these remaining LMW-HA fragments with immunostimulatory potential could induce the polarization of a pathologic Th1/Th17/Th22-pattern of immune response on T lymphocytes. CLINICAL RELEVANCE: The persistence of increased levels of LMW-HA in periodontal tissues after periodontal therapy could favor the recurrence of the disease and further breakdown of periodontal supporting tissues.