Search Results (120)

Background/Objectives: This study aimed to evaluate the gingival crevicular fluid (GCF) levels of fractalkine/CX3CL1 and CX3CR1 in patients with gingivitis and periodontitis before and after non-surgical periodontal therapy. Methods: A total of 90 individuals comprising 30 with stage 3 periodontitis, 30 with gingivitis, and 30 periodontally healthy, were enrolled in the study. Gingivitis and periodontitis patients underwent non-surgical periodontal treatment. GCF samples were collected at baseline and at 1 and 3 months after treatment. CX3CL1 and CX3CR1 were measured by an ELISA analysis. Results: GCF CX3CL1 and CX3CR1 were significantly elevated in patients with periodontitis and gingivitis compared to healthy controls (p < 0.001). The periodontitis patients also showed higher GCF levels of CX3CL1 and CX3CR1 than those with gingivitis (p < 0.001). Significant decreases in GCF CX3CL1 and CX3CR1 were detected at 1 month after periodontal treatment compared to baseline values in both the gingivitis and periodontitis patients (p < 0.001). Moreover, the periodontitis patients exhibited significant decreases in both CX3CL1 and CX3CR1 levels at 3 months post-treatment compared to 1 month (p < 0.001), whereas no significant changes were observed between the two time points in the gingivitis patients (p > 0.05). Conclusions: Our findings suggest that the CX3CL1–CX3CR1 axis might contribute to the inflammatory processes of periodontal diseases and may represent a treatment-responsive component of the local host response. Full article

Background/Objectives: Cigarette smoking is a well-established risk factor for periodontal tissue damage caused by oxidative stress and increased proteolytic activity. Electronic cigarettes (e-cigarettes), marketed as less harmful alternatives, deliver nicotine and reactive compounds that may similarly disrupt periodontal health. However, their molecular effects on clinically healthy periodontal tissues remain unclear. This study aimed to compare oxidative stress-related and matrix-degradative biomarkers in the gingival crevicular fluid (GCF) of cigarette smokers (CS), e-cigarette (EC) users, and non-smokers (NS), and to examine the relationships among these markers. Methods: Sixty individuals, who were systemically and periodontally healthy (20 CS, 20 EC, and 20 NS), were examined. Clinical parameters, including probing depth (PD), clinical attachment level (CAL), plaque index (PI), and bleeding on probing (BOP), were recorded. GCF samples were analyzed for reactive oxygen species (ROS), matrix metalloproteinase-9 (MMP-9), and forkhead box protein O-1 (FOXO-1) using ELISA. Initial group comparisons were descriptive, followed by analysis of covariance (ANCOVA) to adjust for age; PI and PD were included as covariates in separate models. Correlations were assessed using Spearman’s analysis. Results: PD was significantly higher in both EC users and CS compared with NS (p = 0.022). MMP-9 levels were significantly higher in CS than in EC users and NS (p < 0.05), while FOXO-1 concentrations were significantly lower in CS compared with NS (p = 0.0227). ROS levels did not differ significantly among groups (p > 0.05). After adjustment for age, PI, or PD, group differences in MMP-9 and FOXO-1 remained statistically significant, whereas ROS levels remained comparable. FOXO-1 demonstrated positive correlations with ROS and MMP-9 within exposure groups; these associations were considered exploratory. Conclusions: In this cross-sectional study, CS and EC use were associated with altered matrix-regulatory biomarker profiles in clinically healthy periodontal tissues, independent of age and periodontal indices. Causal or temporal inferences cannot be drawn, and longitudinal studies are needed to clarify the long-term periodontal implications of these findings. Full article

Background/Objectives: Mathematical modelling provides a quantitative way to describe the fate and action of drugs in the oral cavity, where transport processes are shaped by salivary flow, pellicle formation, biofilm structure and the wash-out effect of gingival crevicular fluid (GCF). Local pharmacokinetics in the mouth differ substantially from systemic models, and therefore a dedicated framework is required. The aim of this work was to present a structured, physiologically based concept that links in vitro release testing with local pharmacokinetics and pharmacodynamics. Methods: A narrative review with elements of systematic search was conducted in PubMed, Scopus and Web of Science (1980–2025) for publications describing drug release, local PBPK, and PK/PD modelling in the oral cavity. Mathematical formulations were grouped into release kinetics, mini-PBPK transport and local PK/PD relations. Classical models (Higuchi, Korsmeyer–Peppas, Peppas–Sahlin) were integrated with a mini-PBPK structure describing saliva–mucosa–biofilm–pocket interactions. Results: The combined model captures adsorption to pellicle, diffusion within biofilm and wash-out by GCF. It allows simulation of variable clinical conditions, such as inflammation-related changes in Q_GCF, and links local exposure to pharmacodynamic outcomes. Case studies with PerioChip^®, Arestin^®, and Atridox^® demonstrate how mechanistic models explain observed therapeutic duration and low-systemic exposure. Conclusions: The proposed mini-PBPK framework bridges empirical release data and physiological transport in the oral cavity. It supports rational formulation design, optimisation of local dosage, and personalised prediction of drug retention in gingival pockets. This modelling approach can become a practical tool for the development of dental biomaterials and subgingival therapies. Full article

Background/Objectives: End-stage chronic kidney disease (ESKD) represents a complex condition that also impacts oral health. This pilot study evaluates and compares some approaches to oral health assessment and aims to define the specific oral features common in adolescents with ESKD. Methods: A total of 50 children aged 12 to 17 years were examined, including 30 adolescents with ESKD (Group 1) and 20 adolescents without urinary pathology (Group 2). The decayed, missing, filled teeth (DMFT) index, oral hygiene index-simplified, papillary marginal attached index, and periodontal index were used for dental and periodontal assessment. The Milwaukee PH56 device was used to determine salivary pH. Oral microbiota was analyzed by chromatography–mass spectrometry and polymerase chain reaction detection of periodontopathogenic bacteria. Salivary and gingival crevicular fluid (GCF) biomarkers (IL-1β, TNF-α, IL-8, VEGF, sIgA) and total antioxidant capacity (TAC) were determined using an enzyme-linked immunosorbent assay. Results: DMFT did not differ between the groups. Periodontal indices in Group 1 were increased compared to Group 2 (p < 0.0001). Salivary pH in Group 1 was slightly alkaline; in Group 2, it was slightly acidic (p < 0.0001). Oral dysbiosis and periodontopathogenic bacteria were found in ESKD adolescents. Salivary IL-1β, TNF-α, VEGF, and IL-1β in GCF were elevated in Group 1 compared to Group 2 (p < 0.05). TNF-α, IL-8, and VEGF in GCF and TAC in both fluids were lower in Group 1 compared to Group 2 (p < 0.0001). Salivary IL-8 and sIgA in both saliva and GCF did not differ between the groups. Conclusions: ESKD adolescents had poor oral hygiene and significant oral dysbiosis including periodontopathogenic bacteria. Evaluation of biomarkers in saliva and GCF allowed us to vindicate inflammation, dysbiosis severity, and periodontal diseases. Full article

Background/Objectives: Orthodontic tooth movement is a biological process involving coordinated bone resorption and formation in response to mechanical stimulation. The aim of this study was to evaluate the temporal changes in C-terminal telopeptide of type I collagen (CTX), procollagen type I N-terminal propeptide (PINP), and vitamin D-binding protein (VDBP) levels in gingival crevicular fluid (GCF) and saliva during fixed orthodontic treatment, as well as to assess the relationships among these biomarkers. Methods: The study included a total of 27 systemically and periodontally healthy individuals comprising 14 males and 13 females. Clinical periodontal parameters were assessed at three time points: before treatment (T0), at 24–48 h (T1), and on day 40 (T2). GCF and saliva samples were collected at the same time points. Levels of CTX, PINP and VDBP in GCF and saliva were quantified using enzyme-linked immunosorbent assay. The data were analyzed using both parametric and non-parametric statistical tests. Temporal changes across the three time points were evaluated using mixed-effects models, differences between GCF and saliva biomarker levels were assessed using paired tests, and correlations were examined using Spearman correlation analysis. Results: GCF and salivary CTX levels demonstrated a significant increase from T0 to T1, while PINP levels exhibited a substantial rise from T1 to T2 (p < 0.001). Levels of VDBP in both GCF and saliva did not demonstrate significant temporal changes (p > 0.05). Higher VDBP levels in both fluids were found to be negatively associated with increases in CTX and positively associated with increases in PINP (p < 0.05). Furthermore, salivary CTX and VDBP levels exhibited a consistent increase compared to those measured in GCF at all time points (p < 0.05). Conclusions: Fixed orthodontic forces elicit sequential resorptive and formative responses in both GCF and saliva. The potential of VDBP to function as a local modulator is indicated, with the capacity to influence the balance between osteoclastic and osteoblastic activity. The evaluation of these biomarkers in non-invasive biological samples may offer a valuable approach for monitoring bone metabolism throughout orthodontic treatment. Full article

Due to the limitations of SRP, new methods are being sought to support non-surgical periodontal therapy. One of them is the use of antiseptics such as low-concentration sodium hypochlorite gel buffered with amino acids (NaOCl/AA). The aim of the study was to evaluate periodontal parameters and the concentration of metalloproteinase 8 (MMP-8) and interleukin 8 (IL-8) in the gingival crevicular fluid (GCF) after SRP with or without NaOCL/AA gel. The study included 40 periodontal patients randomized to study and control groups. Before SRP, the study group had a gel introduced into pockets with PD ≥ 5 mm. After treatment in both groups, the pocket depth (PD) decreased, there was a CAL gain, and unnoticeable changes in the gingival recession (GR). In the study group, deep pockets accounted for 25% of the sites examined prior to therapy, whereas after therapy, they decreased to 12%. In the control group, the proportion of deep periodontal pockets (PD ≥ 5 mm) fell from 17.46% to 9.05%. No differences were noted between groups. In the study group, there was a significant reduction in the amount of MMP-8 in GCF from 8.32 ng/mL to 5.14 ng/mL after 3 months. No statistically significant difference was observed in the control group. The concentration of IL-8 decreased significantly over time in both groups without differences between them. A single application of the NaOCl/AA gel in deep periodontal pockets does not affect clinical results and IL-8 levels. However, it had a significant effect on the amount of MMP-8. Full article

Background: Chlorhexidine (CHX) is an effective antiseptic rinse for managing gingival inflammation; however, side effects such as staining and altered taste limit its long-term use. StellaLife^® (SL), an herbal-based mouth rinse and a gel, has shown promising in vitro effects, including enhanced biocompatibility and wound healing. This study aimed to compare the clinical efficacy of SL and 0.12% CHX in an experimental gingivitis model. Methods: In this randomized, controlled, cross-over clinical trial, 34 dental students received both treatment regimens in alternating two-week phases following prophylaxis. Group 1 used SL (mouth rinse and the gel) and then crossed over to CHX with placebo gel. Group 2 followed the reverse sequence. Participants refrained from oral hygiene during treatment phases. Clinical parameters and gingival crevicular fluid (GCF) were assessed at baseline and post-treatment. Paired t-tests and Bonferroni corrections were applied (p < 0.05). Bacterial count was determined by an external laboratory using a PCR test. Mean values for bacteria after SL and CHX use measured in genome copies/mL for Aggregatibacter actinomycetemcomitans, P. gingivalis, T. denticola, T. forsythia and F. nucleatum. Results: No statistically significant differences were observed between the SL and CHX groups for PI (p = 0.057), GI (p = 0.960), PD (p = 0.112), BOP (p = 0.895), GR (p = 0.768), CAL (p = 0.112), or GCF (p = 0.951). Both regimens improved periodontal parameters similarly. No significant differences were found between CHX and SL use in respect to periodontal pathogenic bacteria in the oral cavity. Conclusions: SL demonstrated clinical efficacy comparable to CHX in managing experimental gingivitis. Given its favorable safety profile, SL may serve as a promising alternative to CHX, though larger and longer-term studies are warranted. Full article

Gingival crevicular fluid (GCF) reflects both local periodontal inflammation and systemic conditions. This review highlights the role of oxidative stress, oxidised low-density lipoprotein (oxLDL), and apolipoprotein B (apoB) as molecular links between periodontitis and metabolic disorders. Elevated GCF levels of oxLDL and apoB indicate enhanced vascular permeability and local oxidative modification, particularly in diabetes. Furthermore, oxLDL promotes the formation of neutrophil extracellular trap (NET) via connecting oxidative stress with immune-mediated tissue injury. These insights establish GCF as a valuable, non-invasive biomarker for understanding the interplay between periodontal and systemic diseases. Full article

Background and Objectives: Orthodontic tooth movement triggers micro-trauma in the periodontal ligament, leading to a balanced process of bone resorption and apposition mediated by local inflammatory responses. Monitoring N-telopeptide levels in gingival crevicular fluid (GCF) and applying low-intensity laser biostimulation can help optimize mechanical loading, reduce adverse effects, and enhance tissue remodeling during treatment. Materials and Methods: This study had a split-mouth observational design. From 30 patients with ages between 20 and 50, with standardized fixed orthodontic treatment, GCF samples were collected from both control and laser-treated hemiarches before and 14 days after appliance activation. Low-intensity laser therapy (LLLT) was applied to selected sites to assess its effect on N-telopeptide levels, a marker of bone resorption, with samples analyzed via ELISA and results compared statistically to evaluate the impact of laser biostimulation during orthodontic treatment. Statistical analysis was performed using paired t-tests or Wilcoxon tests for two-group comparisons. Results: N-telopeptide levels in gingival crevicular fluid increased significantly from baseline (T0) to 14 days (T1) in both the laser-treated (HL) and control (sham) hemiarches (HC), with higher values observed in the lasered side. Statistical analysis confirmed significant differences between HL and HC at T1 (p < 0.0001), as well as between each T1 group and baseline, indicating that low-intensity laser therapy enhanced bone resorption activity during orthodontic tooth movement. Conclusions: N-telopeptide exhibited higher values in the hemiarches where laser therapy was applied than in the control ones. This provides a rationale for using laser biostimulation as an adjuvant during orthodontic treatment to modulate tissue restructuring. Full article

Objective: We aimed to synthesize paired pre/post human evidence on how Th17-axis cytokines (IL-17A, IL-21, IL-22, IL-23 and related markers) change after non-surgical periodontal therapy (NSPT) by biospecimen (gingival crevicular fluid [GCF], saliva, serum) and time window. Material and methods: We performed a PRISMA-guided systematic review of non-randomized pre/post cohorts and clinical trials. Databases (PubMed, Embase, Scopus, Cochrane) were searched; two reviewers performed selection, data extraction, ROBINS-I risk-of-bias appraisal, and GRADE certainty assessment. Due to heterogeneity in sampling/assays and incomplete variance reporting, a qualitative direction-of-effect synthesis was prespecified for ≤4 weeks, ~6–8 weeks, and ~3–6 months. Results: Twelve studies (total n = 897) met inclusion (8 GCF; 5 blood-derived (serum/plasma) cohorts; one saliva). Most GCF cohorts reported decreases in IL-17A within ~6–8 weeks post-NSPT (≥4 cohorts), with one early 4-week cohort showing a concentration increase but an unchanged total amount due to reduced GCF volume. IL-23 generally declined locally and declined by ~3 months systemically in aggressive periodontitis. Serum IL-17A changes were smaller/variable (two cohorts reported decreases within 1–6 months), and one cohort showed a reduced IL-17A:IL-17E ratio at ~25 weeks. Heterogeneity precluded meta-analysis; we undertook a direction-of-effect synthesis. Conclusions: NSPT is likely associated with the early local down-regulation of Th17-axis activity (notably GCF IL-17A), when systemic signals are smaller and delayed. Given moderate–serious risk of bias and pre-analytical heterogeneity, the certainty of evidence is low to very low; Th17-axis biomarkers are not yet suitable for clinical decision-making. Full article

Background/Objectives: This study aimed to investigate specific biomarkers of oxidative stress within gingival crevicular fluid (GCF) and plasma obtained from children with leukemia compared to healthy subjects, in relation to the oral hygiene status and gingival inflammatory status, in order to identify a possible association linking childhood leukemia with gingival inflammation. Methods: The study comprised biomarker analysis from 97 children divided into two groups: 47 leukemia subjects and 50 systemically healthy children in the control group. The GCF and plasma specimens were analyzed to determine values of 8-OHdG (8-hydroxydeoxyguanosine) and SOD (superoxide dismutase) using ELISA (enzyme-linked immunosorbent assay) techniques, while MDA (malondialdehyde) values were measured through colorimetry. Results: We found elevated plasma expressions of all investigated biological parameters among leukemic children relative to the control group. GCF measurements highlighted raised 8-OHdG and SOD in leukemic individuals, while MDA recorded no significant shift between the groups. The statistical analysis also revealed a possible GCF and plasma SOD levels associated with the oral hygiene and gingival inflammatory status. Conclusions: The increased expression of oxidative stress markers we found in children with leukemia underlines the heightened inflammatory and oxidative burden in this category of population, yet additional studies are needed to clarify the intricate relation between systemic oxidative stress, oral biomarkers and gingival health outcomes in children, especially in children with critical systemic alterations such as leukemia. Full article

Background/Objectives: Orthodontically induced bone remodeling is a complex process, driven by the interaction between osteoblasts, osteoclasts and various biochemical mediators, in response to mechanical forces applied to the teeth. Monitoring this process can be achieved by identifying biomarkers in gingival crevicular fluid (GCF), a dynamic and non-invasive method. Laser therapy, widely used in other medical fields for bio-stimulation and surgery, does not yet benefit from a standardized protocol in orthodontics. The aim of this study was to evaluate the advantages of using laser therapy during orthodontic treatment by analyzing osteocalcin (OC) in gingival crevicular fluid (GCF). Methods: Based on the inclusion and exclusion criteria, we selected 30 patients who presented dentoalveolar disharmony with crowding, who benefited from fixed orthodontic treatment, using edgewise brackets with the same slot size for all subjects. Laser therapy was performed randomly on one hemiarch (HL), right or left, for each patient, randomly chosen at time T0, after activation of the orthodontic appliance. On the other side, the control hemiarch (HC), the same protocol was followed, but without active light. Laser therapy was performed with a dental laser, with a power of 12 watts, setting the periodontology working mode. GCF was collected at baseline, before activation of the orthodontic appliance (time T0) and 14 days after its activation (time T1) from the control hemiarch (HC) and laser hemiarch (HL). Determination of OC levels, as a marker of bone apposition, was performed by the enzyme-linked immunosorbent assay (ELISA) method. To evaluate laser therapy, OC levels were assessed comparatively between HL and HC. Results: Comparing OC values at times T0 and T1 for HL, we obtained a statistically significant difference (p < 0.0001). No statistically significant difference was detected when comparing OC values in HC between T0 and T1 (p = 0.2422). A statistically significant difference was observed between HC and HL at T1 (p < 0.0001). Conclusions: The higher OC levels observed in the hemiarches where laser therapy was applied, compared to the controls, demonstrate its effectiveness as an adjuvant in bone remodeling during orthodontic treatment. Full article

Periodontitis (PD) is a multifactorial, progressive inflammatory disease affecting the teeth-supporting tissues, characterized by an imbalance of the oral microbiota and the presence of bacterial biofilms leading to host response. Nowadays, reliable biochemical markers for early and objective diagnosis, and for predicting disease progression, are still lacking. Our previous proteomic investigations revealed the significant overexpression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in periodontal pocket tissue, gingival crevicular fluid (GCF), and tooth-surface-collected material (TSCM) from PD patients in comparison to periodontally healthy controls, proposing it as a possible biomarker of PD. This study aimed to evaluate the expression of GAPDH in saliva, a more accessible, non-invasive, and clinically relevant oral sample. The whole saliva was analyzed by a preliminary mass spectrometry-based proteomic approach, identifying significantly increased levels of GAPDH also in salivary samples from periodontal-affected subjects. These data were further validated by enzyme-linked-immunosorbent assay (ELISA). Additionally, protein–protein interaction networks were generated through the Human Protein Atlas database, using different datasets (OpenCell, IntAct, and BioGRID). Bioinformatic analysis provided noteworthy GAPDH-associated networks potentially relevant to periodontal pathology. The scientific significance of this study lies in the detection of salivary GAPDH as a novel strategy to advance periodontal clinical diagnostics from the perspective of a non-invasive screening test. In correlation with other protein markers, salivary GAPDH could constitute a promising set of distinctive and predictive targets to enhance early diagnosis of PD, disease monitoring, and treatment planning in periodontology. Full article

Periodontitis is a globally prevalent oral disease and is closely associated with various systemic diseases. Periodontitis arises from dynamic and complex interactions between polymicrobial communities and host immune responses. Extracellular vesicles (EVs) are circulating subcellular particles carrying multiple signaling molecules. EVs play a key role in intercellular communication, and hold promise for diagnostic and therapeutic purposes. Bacterial extracellular vesicles (BEVs), released from oral pathogens, have been implicated in delivering virulence factors to host cells. In contrast, host cell-derived EVs (CEVs), secreted by periodontal cells, contain molecular cargo that reflect disease status. Both BEVs and CEVs contribute to periodontitis progression by exacerbating inflammation and tissue destruction, and they may also influence related systemic diseases. Moreover, the molecular components of EVs derived from saliva and gingival crevicular fluid (GCF) show potential as diagnostic biomarkers for periodontitis. In addition, mesenchymal stem cell-derived EVs (MSC-EVs) exhibit therapeutic potential in periodontitis, and engineering approaches have been developed to enhance their therapeutic efficacy and accelerate clinical translation. This review summarizes recent advances in understanding the pathogenic, diagnostic, and therapeutic roles of EVs in periodontitis and discusses current challenges and future directions toward their clinical application. Full article

Background/Objectives: Our study aimed to evaluate the oral health status associated with levels of certain inflammatory biomarkers in the gingival crevicular fluid (GCF) and plasma of children and adolescents with leukemia, in comparison to healthy subjects, in order to assess the correlation between pediatric leukemia and gingivo-periodontal alterations. Methods: The study was conducted on 97 subjects, divided into two groups: the study group, n = 47 leukemia subjects, and the control group, n = 50 healthy subjects. The collected GCF and plasma samples were analyzed for interleukins IL-1β, IL-6 and IL-17α and transforming growth factor TGF-β1 values using ELISA (enzyme-linked immunosorbent assay) techniques. Results: IL-6, IL-17α, and TGF-β1 recorded higher values for leukemia subjects, both in the GCF and plasma, compared to healthy subjects. Our results also pointed out higher gingival fluid IL-1β values in children with leukemia compared to the control group. Conclusions: Elevated expressions of IL-1β in the GCF and IL-6, IL-17α, and TGF-β1, both systemic and local, in the GCF of children with leukemia were associated with oral hygiene status and gingival inflammation, respectively. All inflammatory biomarkers generally tended to rise in close correlation with oral hygiene worsening and gingival inflammation extension; however, IL-1β in the GCF and plasma, plasma IL-6, and gingival fluid IL-17α pointed out a stronger correlation with gingival inflammation status. Full article