Search Results (118)

Background and Objectives: Periodontitis is a common chronic inflammatory disease and a leading cause of tooth loss worldwide. Traditional diagnostic methods, such as probing and radiographic assessment, are retrospective and fail to detect ongoing disease activity. In recent years, salivary biomarkers and oral microbiome profiling have emerged as promising tools for earlier detection and precision-based management. The aim of this review is to synthesize current evidence on salivary and microbiome-derived biomarkers in periodontitis and to evaluate their translational potential in diagnostics and therapy. Materials and Methods: A narrative review was performed using PubMed, Scopus, and Web of Science to identify studies published between 2020 and 2025. Search terms included periodontitis, salivary biomarkers, oral microbiome, dysbiosis, and precision therapy. Priority was given to systematic reviews, meta-analyses, and translational studies that addressed diagnostic or therapeutic applications. Eligible publications included English-language original studies and reviews reporting on the diagnostic or therapeutic relevance of salivary or microbiome biomarkers in periodontitis. Results: Salivary biomarkers such as cytokines, matrix metalloproteinases (MMPs), oxidative stress markers, microRNAs, and extracellular vesicles (EVs) show consistent associations with disease activity and treatment outcomes. Oral microbiome studies reveal that both classical pathogens and community-level dysbiosis contribute to disease risk. Translational advances include chairside immunoassays, biosensors, lab-on-a-chip devices, and artificial intelligence (AI)-driven analyses. Biomarker-guided therapies—such as microbiome modulation, natural bioactive compounds, host-response modulation, and smart biomaterials—are being evaluated with increasing frequency in translational studies. Conclusions: By integrating salivary and microbiome biomarkers with novel diagnostic technologies and emerging therapies, this review complements existing systematic evidence and offers a translational roadmap toward precision periodontology. Full article

Objective: This study aimed to validate the clinical utility of a salivary molecular platform (Oral Predict^®) for periodontal pathogen detection across preventive, therapeutic, and maintenance settings. Methods: A longitudinal randomized study was conducted involving 78 adults who provided saliva samples at baseline, one month, and three months after professional dental hygiene. Participants were randomized into two groups: control group (n = 39) and probiotic group with Oral Predict^® probiotic supplementation (n = 39). Crude saliva was processed directly without nucleic acid extraction and analyzed by multiplex real-time PCR using either the compact Real-time PCR system or standard thermocyclers. Results: At baseline, Fusobacterium nucleatum was the most prevalent pathogen (84.6%), followed by Tannerella forsythia (53.8%) and Porphyromonas gingivalis (46.2%). The Total Pathogen Burden Score (TPBS) showed progressive increases with age, smoking, and poor oral hygiene, and was significantly higher in participants with gingival bleeding. Among individual pathogens, no significant associations were observed with periodontitis staging or grading. Professional hygiene induced mean reductions of 1–2 logs across all pathogens, with TPBS decreasing from 8.7 ± 3.2 to 4.1 ± 2.8 (p < 0.001). At three months, 69.2% of the control group experienced bacterial rebound, whereas 85% of probiotic users sustained or improved bacterial reductions. Conclusions: Salivary molecular testing provides a robust, non-invasive approach for periodontal pathogen detection, treatment monitoring, and long-term maintenance assessment. The flexibility of the Oral Predict^® platform across point-of-care and laboratory settings, combined with automated interpretation, supports integration into preventive protocols and personalized periodontal care. These findings demonstrate the potential of saliva-based molecular diagnostics to shift periodontal management from reactive to predictive and precision-based strategies. Full article

Background: Tooth preparation design strongly influences the long-term success of fixed prosthodontic restorations, affecting periodontal stability and esthetic outcomes. Conventional horizontal designs such as chamfer and shoulder remain widely used but present biological and technical limitations. The Biologically Oriented Preparation Technique (BOPT), a vertical approach, has been proposed as an alternative. Methods: This narrative review synthesizes evidence from clinical trials, histological investigations, and systematic reviews, comparing horizontal preparations with BOPT with emphasis on periodontal parameters and the role of digital workflows. Results: Horizontal designs provide predictable outcomes but may predispose to inflammation and marginal instability, especially with subgingival margins. BOPT has been associated with greater gingival thickness, stable probing depths, and favorable esthetic results, with prospective studies reporting stability for up to 10 years. Integration with CAD/CAM workflows appears to enhance precision and reproducibility. Conclusions: BOPT shows promising periodontal and esthetic benefits, particularly in thin gingival biotypes and esthetically demanding cases. However, current evidence is limited, and the available studies do not allow firm conclusions about superiority over conventional designs. Further randomized controlled trials with large cohorts and long-term follow-up are required before definitive clinical recommendations can be made. Full article

Background: Diabetes mellitus (DM), periodontal disease (PD), and cardiovascular disease (CVD) are highly prevalent global health conditions with overlapping pathophysiological mechanisms. Emerging evidence suggests a bidirectional and synergistic relationship among them, driven by chronic inflammation, immune dysregulation, oxidative stress, and microbial dysbiosis. Objective: This review synthesizes current literature on the interconnectedness of DM, PD, and CVD, emphasizing shared molecular pathways, clinical implications, and opportunities for integrated management. Methods: A systematic review and narrative synthesis of recent clinical trials, observational studies, and multi-omics investigations was conducted to explore the mechanisms linking these three conditions. A structured literature search was performed across PubMed, Scopus, and Web of Science from database inception until 30 June 2025. Key findings were contextualized within systems biology, precision medicine, and real-world clinical strategies. Results: DM exacerbates periodontal inflammation and accelerates tissue destruction via hyperglycemia-induced inflammatory mediators, while periodontitis worsens glycemic control and insulin resistance. Both conditions independently elevate cardiovascular risk, and their co-occurrence significantly amplifies the incidence of adverse cardiovascular events. Shared biomarkers such as Interleukin (IL)-6, Tumor Necrosis Factor (TNF)-α, and CRP, as well as overlapping genetic and epigenetic signatures, underscore a common inflammatory axis. Periodontal therapy has demonstrated modest but meaningful benefits on glycemic control and endothelial function, while cardiometabolic therapies (e.g., statins, Glucagon-Like Peptide (GLP-1) receptor agonists, SGLT2 inhibitors) show potential to improve periodontal outcomes. Probiotics, microbiome-targeted therapies, and AI-based risk models are emerging as future tools. Conclusions: DM, PD, and CVD form a mutually reinforcing triad mediated by systemic inflammation and metabolic dysregulation. Integrated, multidisciplinary care models and precision health strategies are essential to address this inflammatory burden and improve long-term outcomes. Further large-scale interventional trials and mechanistic human studies are needed to establish causal links and optimize combined therapeutic approaches. Full article

Mandibular second molar (MM2) impaction presents a relatively rare but complex orthodontic challenge, with potential consequences for occlusal function, periodontal health, and adjacent teeth. The aim of the article is to share data on the design and protocols of working with digitally designed systems for Printed Dento-alveolar Anchorage (PDaA) used in orthodontic traction of MM2. Accuracy in design comes from incorporating intraoral scans with CBCT files when planning the support system. The customized PDaA has an extension in the retention area of MM2 and allows multiple points of force application and vector control for precise tooth movement. The clinical flow includes surgical exposure and button placement on MM2, orthodontic traction using elastic elements attached to the PDaA, periodic activation every 3–4 weeks until the introduction of MM2 into the dental arch, and continuing with complete treatment of the entire orthodontic malocclusion. The clinical results demonstrated successful eruption and vertical leveling of MM2, stable anchorage, and absence of adverse effects on supporting teeth. Therapy with PDaA was well tolerated by patients, and did not disrupt aesthetics. This study highlights the potential of digital orthodontics to deliver personalized, biomechanically efficient solutions for molar impaction cases. Full article

Nisin, a food preservative lantibiotic produced by Lactococcus lactis, exhibits potent antimicrobial activity against a wide range of Gram-positive pathogens, including antibiotic-resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA). This study explores the development of a novel nano drug delivery platform comprising nisin-loaded niosomes, formulated via microfluidic mixing, and integrated into fast-dissolving oral films for targeted buccal administration. Microfluidic synthesis enabled the precise control of critical parameters including the flow rate ratio, surfactant composition, and lipid concentration, resulting in uniform niosomal vesicles with optimal size distribution (100–200 nm), low polydispersity index, and high encapsulation efficiency. Span 40 and Span 60 were employed as non-ionic surfactants, stabilized with cholesterol to improve bilayer rigidity and drug retention. The encapsulated nisin demonstrated improved physicochemical stability over time and protection against proteolytic degradation, thus preserving its antimicrobial potency. The niosomal suspensions were subsequently incorporated into polymer-based oral films as a final dosage form composed of polyvinyl alcohol (PVA) as the primary film-forming polymer, polyethylene glycol 400 (PEG400) as a plasticizer, and sucralose and mint as a sweetener and flavoring agent, respectively. A disintegrant was added to accelerate film dissolution in the oral cavity, facilitating the rapid release of niosomal nisin. The films were cast and evaluated for thickness uniformity, mechanical properties, disintegration time, surface morphology, and drug content uniformity. The dried films exhibited desirable flexibility, rapid disintegration (<30 s), and consistent distribution of nisin-loaded vesicles. In vitro antimicrobial assays confirmed that the bioactivity of nisin was retained post-formulation, showing effective inhibition zones (16 mm) against Bacillus subtilis. This delivery system offers a promising platform for localized antimicrobial therapy in the oral cavity, potentially aiding in the treatment of dental plaque, oral infections, and periodontal diseases. Overall, the integration of microfluidic-synthesized nisin niosomes into oral films presents a novel, non-invasive strategy for enhancing the stability and therapeutic efficacy of peptide-based drugs in mucosal environments. Physicochemical characterization of the niosomes and niosome films was performed using Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) to evaluate thermal stability and scanning electron microscopy (SEM) to assess surface morphology. In vitro peptide release studies demonstrated sustained release from both niosomal suspensions and film matrices, and the resulting data were further fitted to established kinetic models to elucidate the underlying drug release mechanisms. This delivery system offers a promising platform for localized antimicrobial therapy in the oral cavity, potentially aiding in the treatment of dental plaque, oral infections, and periodontal diseases. Overall, the integration of microfluidic-synthesized nisin niosomes into oral films presents a novel, non-invasive strategy for enhancing the stability and therapeutic efficacy of peptide-based drugs in mucosal environments. Full article

Background and Objectives: Cone Beam Computed Tomography (CBCT) offers high-resolution, three-dimensional imaging for detecting apical periodontitis (AP) and evaluating the technical quality of endodontic treatments. This study aimed to investigate the diagnostic value of CBCT in identifying endodontic failures and periapical lesions and to explore the clinical patterns associated with these findings in a Romanian patient cohort. Materials and Methods: A retrospective study was conducted on 258 patients (with 876 root canal-treated teeth), all of whom underwent CBCT imaging between October 2024 and April 2025 at a private radiology center in Craiova, Romania. Of the 876 treated teeth, 409 were diagnosed with apical periodontitis. Patients were present for endodontic treatment at the Endodontics Clinic of the Faculty of Dentistry, University of Medicine and Pharmacy of Craiova. With the patients’ consent, 3D radiological examinations were recommended for better case planning and accurate diagnosis. The periapical status and technical parameters of root canal fillings were assessed using the CBCT-PAI index and evaluated by three calibrated observers. Associations with demographic, clinical, and behavioral factors were statistically analyzed. Results: Apical periodontitis was detected in 46.69% of the teeth examined during the study period, with CBCT-PAI score 3 being the most prevalent. Poor root canal obturation quality (underfilling, overfilling, and voids) was significantly associated with periapical pathology. Chronic lesions were more common than acute ones, especially in older patients. The number of teeth with endodontic treatments and no AP, as well as the number of teeth with AP, was significantly lower for patients with acute AP, indicating the more severe impact of chronic AP on the patients’ oral health status. CBCT allowed the precise localization of missed canals and assessment of lesion severity. Conclusions: Within the limits of a retrospective, referral-based cohort, CBCT aided the detection of periapical pathology in root canal-treated teeth (46.69%). These findings do not represent population-based rates but support the selective use of CBCT, in line with current ESE guidance, for complex cases or when conventional imaging is inconclusive. Full article

Background/Objectives: Tooth autotransplantation is a natural tooth replacement method that preserves the periodontal ligament, supporting root development and alveolar bone remodeling. Unlike dental implants, autotransplanted teeth maintain sensory function and adapt better to the mouth. Although once overlooked, new surgical, imaging, and regenerative advances have revived interest in this technique. This narrative review explores the renewed interest in tooth autotransplantation by assessing its benefits, success rates, technological advancements, and role in modern dentistry while evaluating its advantages, limitations, and potential impact on dental care. Methods: A narrative approach was used to provide a comprehensive and descriptive overview of current knowledge on tooth autotransplantation. A literature search was conducted in PubMed, Scopus, and Google Scholar using keywords such as “tooth autotransplantation”, “biological tooth replacement”, “periodontal ligament”, and “dental implants alternative”. English-language articles published between 2000 and 2025 were included, covering clinical trials, reviews, and relevant case reports. Selection focused on studies discussing biological mechanisms, clinical techniques, technological advances, and treatment outcomes. Results: Success rates range from 80% to 95%, with better predictability in younger patients with immature donor teeth. Long-term viability depends on preserving the PDL and performing atraumatic extractions. However, challenges such as root resorption, ankylosis, and appropriate case selection remain significant considerations. Technological advancements, including CBCT, 3D-printed surgical guides, and biomimetic storage media, have improved surgical precision and clinical outcomes. Conclusions: Tooth autotransplantation is an effective and cost-effective alternative to dental implants, particularly for growing patients or when implants are not suitable. While success depends on surgical skill and proper case selection, improvements in imaging and regenerative techniques have made outcomes more predictable. Future advances in bioengineering, AI-based planning, and regenerative therapies are likely to expand their use in modern dentistry. Full article

The Maxillary Skeletal Expander (MSE) is used for maxillary expansion in adolescents and young adults. Virtual planning using 3D models, CBCT and 3D printers help in case selection, appliance design and fabrication. Using the proposed digital workflow, the accuracy of the patient selection phase and appliance delivery are increased, and the required number of visits to the clinic is decreased. The MSE serves as a guide for the insertion of mini-implants, reducing the number of appointments needed for installation. (1) Introduction: Mini-Implant-Assisted Rapid Palatal Expansion (MARPE) appliances, like the MSE, decrease the side effects that regular tooth-anchored appliances have on dental and periodontal structures, especially for skeletally mature patients, combining palatal anchorage with dental support for guidance. The digital planning of the insertion sites, length and angulation of the mini screws, and the fabrication of the 3D-printed appliance that stands as a mini-implant insertion guide give an undeniable precision. (2) Materials and methods: The laboratory steps used in the digital design and fabrication, and clinical steps needed for the insertion protocol are described. (3) Discussions: The individual assessment of the anatomical structures and the use of virtual integrated dental impressions and CBCT increase the accuracy of diagnosis, appliance fabrication and treatment progress. Implementing a digital workflow for mini-implant-supported expansion is a real advantage for both dental teams and patients. (4) Conclusions: The wide range of advantages and the ease of the process support the introduction of this digital workflow in every orthodontic practice. Full article

Periodontal disease is a widespread chronic condition linked to systemic illnesses such as cardiovascular disease, diabetes, and adverse pregnancy outcomes. Despite its global burden, population-specific studies on its risk factors remain limited, particularly in Central and Eastern Europe. The SANA-biome Project is a cross-sectional, community-based study designed to investigate the biological and social determinants of periodontal disease in Romania, a country with disproportionately high oral disease rates and minimal microbiome data. This protocol will integrate metagenomic, proteomic, and metabolomic data of the oral microbiome from saliva and dental calculus samples with detailed sociodemographic and lifestyle data collected through a structured 44-question survey. This study is grounded in two complementary frameworks: the IMPEDE model, which conceptualizes inflammation as both a driver and a consequence of microbial dysbiosis, and Ecosocial Theory, which situates disease within social and structural contexts. Our aims are as follows: (1) to identify lifestyle and behavioral predictors of periodontal disease; (2) to characterize the oral microbiome in individuals with and without periodontal disease; and (3) to evaluate the predictive value of combined microbial and sociodemographic features using statistical and machine learning approaches. Power calculations based on pilot data indicate a target enrollment of 120 participants. This integrative approach will help disentangle the complex interplay between microbiological and structural determinants of periodontal disease and inform culturally relevant prevention strategies. By focusing on an underrepresented population, this work contributes to a more equitable and interdisciplinary model of oral health research and supports the development of future precision public health interventions. Full article

Background and objective: Periodontitis, a chronic inflammatory disease driven by host immune dysregulation, leads to progressive destruction of periodontal tissues. This study employed an integrative approach combining single-cell transcriptomics, hierarchical weighted gene co-expression network analysis (hdWGCNA), and deep learning algorithms to identify key biomarkers associated with neutrophil degranulation in periodontitis, aiming to establish diagnostic models for early detection and precision interventions. Methods: We integrated single-cell RNA sequencing (scRNA-seq) data from human gingival tissues with bulk transcriptomic datasets. Pathogenic neutrophil subsets were characterized via pseudotime trajectory and cell–cell communication analyses. Hierarchical weighted gene co-expression network analysis (hdWGCNA) identified functional modules linked to degranulation. Machine learning and a convolutional neural network (CNN) model combining gene expression and immune cell profiles were developed for diagnosis. Results: scRNA-seq revealed a neutrophil subpopulation significantly increased infiltration in periodontitis, with cell–cell communication and pseudotime trajectory analyses demonstrating amplified inflammatory crosstalk. hdWGCNA identified the turquoise module enriched in PD-KEY-Neutrophils, containing hub genes linked to neutrophil degranulation and complement activation. Immune infiltration and non-negative matrix factorization linked high-degranulation neutrophil signatures to the periodontal immunity microenvironment. Machine learning demonstrated that the neutrophil degranulation-associated genes effectively distinguish diseased gingival tissue, suggesting their potential to predict periodontitis. Finally, integrating transcriptomic and immunological data, we developed a gene-immune CNN deep learning model accurately diagnosed periodontitis in diverse cohorts (AUC = 0.922). Conclusions: Our study identified a pathogenic neutrophil subpopulation driving periodontitis through degranulation and inflammation. The neutrophil degranulation genes serve as critical biomarkers, offering new insights for clinical diagnosis and treatment of periodontitis. Full article

The oral microbiota, long recognized for their role in local pathologies, are increasingly implicated in systemic disorders, particularly cardiovascular disease (CVD). This review focuses on emerging evidence linking oral dysbiosis to neuroglial activation and autonomic dysfunction as key mediators of cardiovascular pathology. Pathogen-associated molecular patterns, as well as gingipains and leukotoxin A from Porphyromonas gingivalis, Fusobacterium nucleatum, Treponema denticola, Aggregatibacter actinomycetemcomitans, etc., disrupt the blood–brain barrier, activate glial cells in autonomic centers, and amplify pro-inflammatory signaling. This glia driven sympathetic overactivity fosters hypertension, endothelial injury, and atherosclerosis. Crucially, sex hormones modulate these neuroimmune interactions, with estrogen and testosterone shaping microbial composition, glial reactivity, and cardiovascular outcomes in distinct ways. Female-specific factors such as early menarche, pregnancy, adverse pregnancy outcomes, and menopause exert profound influences on oral microbial ecology, systemic inflammation, and long-term CVD risk. By mapping this oral–brain–heart axis, this review highlights the dual role of oral microbial virulence factors and glial dynamics as mechanistic bridges linking periodontal disease to neurogenic cardiovascular regulation. Integrating salivary microbiome profiling with glial biomarkers [e.g., GFAP (Glial Fibrillary Acidic Protein) and sTREM2 (soluble Triggering Receptor Expressed on Myeloid cells 2)] offers promising avenues for sex-specific precision medicine. This framework not only reframes oral dysbiosis as a modifiable cardiovascular risk factor, but also charts a translational path toward gender tailored diagnostics and therapeutics to reduce the global CVD burden. Full article

Fusobacterium nucleatum (F. nucleatum), a Gram-negative anaerobe traditionally associated with periodontal disease, has recently emerged as a putative contributor to gastric carcinoma (GC) pathogenesis. Beyond its detection in gastric tissues, particularly in patients negative for Helicobacter pylori (H. pylori) or in advanced GC cases, F. nucleatum exerts diverse oncogenic effects. It promotes GC progression by modulating the tumor microenvironment through IL−17/NF-κB signaling, inducing tumor-associated neutrophils (TANs), upregulating PD-L1 expression, and enhancing immune evasion. Moreover, it increases tumor invasiveness via cytoskeletal reorganization, while extracellular vesicles (EVs) induced by the infection contribute to tumor cell proliferation, invasion, and migration. Clinically, its presence correlates with increased tumor mutational burden (TMB), venous thromboembolism, and poor prognosis. This review summarizes the current evidence regarding the emerging role of F. nucleatum in gastric tumorigenesis, examines its potential utility as a diagnostic and prognostic biomarker within the framework of precision oncology, and outlines the molecular methodologies presently employed for its detection in gastric tissue specimens. Full article

Objectives: The objective of this narrative review was to evaluate the clinical challenges encountered in the application of the 2018 AAP/EFP Classification of Periodontitis. Methods: Electronic and manual searches were conducted to identify studies reporting diagnostic accuracy and inter- and intra-examiner agreement when using the 2018 Classification, both with and without the aid of implementation tools. Results: Eleven studies were included, encompassing a total of 459 clinical cases. Overall, 852 examiners participated, with 31 gold-standard examiners providing the reference diagnoses. General dentists often exhibited lower diagnostic accuracy and consistency compared to students and periodontal experts. Diagnostic challenges were observed in staging, particularly distinguishing between Stage III/IV and gingivitis/Stage I. Grading reliability was reduced in the absence of longitudinal data and high-level modifying factors. This review also explored difficulties in reporting ‘hopeless teeth’ and assigning the extent of periodontitis. Education, training, and implementation tools substantially improved diagnostic accuracy and consistency, increasing the agreement with reference diagnosis and strengthening inter- and intra-examiner agreement. Conclusions: The application of the 2018 Classification showed notable variability in diagnostic accuracy and inter- and intra-examiner agreement. Improving clinician experience and training and incorporating diagnostic aids and emerging AI technologies has the potential to enhance diagnostic accuracy and consistency, which are essential for precisely estimating periodontitis prevalence, interpreting research findings, and determining prognosis and treatment needs. Full article

Tooth development (odontogenesis) is regulated by interactions between epithelial and mesenchymal tissues through signaling pathways such as Bone Morphogenetic Protein (BMP), Wingless-related integration site (Wnt), Sonic Hedgehog (SHH), and Fibroblast Growth Factor (FGF). Mesenchymal stem cells (MSCs) derived from dental tissues—including dental pulp stem cells (DPSCs), periodontal ligament stem cells (PDLSCs), and dental follicle progenitor cells (DFPCs)—show promise for regenerative dentistry due to their multilineage differentiation potential. Epigenetic regulation, particularly DNA methylation, is hypothesized to underpin their distinct regenerative capacities. This study reanalyzed publicly available DNA methylation data generated with Illumina Infinium HumanMethylation450 BeadChip arrays (450K arrays) from DPSCs, PDLSCs, and DFPCs. High-confidence CpG sites were selected based on detection p-values, probe variance, and genomic annotation. Principal Component Analysis (PCA) and hierarchical clustering identified distinct methylation profiles. Functional enrichment analyses highlighted biological processes and pathways associated with specific methylation clusters. Noncoding RNA analysis was integrated to construct regulatory networks linking DNA methylation patterns with key developmental genes. Distinct epigenetic signatures were identified for DPSCs, PDLSCs, and DFPCs, characterized by differential methylation across specific genomic contexts. Functional enrichment revealed pathways involved in odontogenesis, osteogenesis, and neurodevelopment. Network analysis identified central regulatory nodes—including genes, such as PAX6, FOXC2, NR2F2, SALL1, BMP7, and JAG1—highlighting their roles in tooth development. Several noncoding RNAs were also identified, sharing promoter methylation patterns with developmental genes and being implicated in regulatory networks associated with stem cell differentiation and tissue-specific function. Altogether, DNA methylation profiling revealed that distinct epigenetic landscapes underlie the developmental identity and differentiation potential of dental-derived mesenchymal stem cells. This integrative analysis highlights the relevance of noncoding RNAs and regulatory networks, suggesting novel biomarkers and potential therapeutic targets in regenerative dentistry and orthodontics. Full article