Osteoporosis is a systemic disease characterized by reduced bone density. The aim of this exploratory, retrospective controlled pilot study following STROBE guidelines, was to descriptively assess periapical lesion healing following endodontic treatment in patients with osteoporosis compared with matched healthy controls and to generate hypotheses for future studies. Digital X-ray images of patients who underwent endodontic treatment at a German university dental clinic between January 2011 and December 2020 were evaluated. Patients with radiographically visible periapical lesions, a follow-up radiograph obtained 6–12 months after treatment, and a documented diagnosis of osteoporosis were included. Changes in periapical lesion size and Periapical Index (PAI) scores were assessed and compared with an age- and tooth-group-matched control cohort. Given the limited sample size, analyses were considered exploratory. Out of 103,385 screened patients, 13 patients with osteoporosis (4 male, 9 female) fulfilled all inclusion criteria and were matched to 13 healthy controls. Both groups demonstrated a reduction in periapical lesion size over time (mean change: -2.47 mm in the osteoporosis group and − 1.90 mm in controls). A mean improvement of one PAI grade was observed in both cohorts. No statistically significant group differences were detected. Within the limitations of this exploratory pilot study, no statistically significant differences in radiographic periapical healing were observed between patients with osteoporosis and matched healthy controls. Due to the limited sample size and the resulting limited statistical significance, these findings should be interpreted with caution, and further studies are needed to clarify the possible influence of osteoporosis on endodontic healing. With demographic change, the potential influence of osteoporosis on endodontic healing is of increasing clinical interest. This study highlights both feasibility and methodological challenges when addressing this question in retrospective clinical cohorts.

OBJECTIVES:Dental resins for single-tooth restorations undergo shrinkage during manufacture. The shrinkage can be compensated for by adjusting the internal tooth-restoration gap. This study examines the volume precision and trueness of additive manufactured inlays based on different gap widths. METHODS:Indirect restorations were fabricated with a dental resin (VarseoSmile Crown plus) on a digitised molar with a mesio-occlusal-distal cavity. A total of 42 inlays, with spacers ranging from 0 to 130 µm, were printed in 10 µm increments. Three print batches (P1, P2 and P3) were produced for each gap width. The printed inlays were digitised using an intraoral scanner. To evaluate volume precision, the intraclass correlation coefficient (ICC) was calculated. Trueness was analysed in relation to initial planning with a paired t-test. RESULTS:The printed inlays exhibited a mean shrinkage of 6.2% compared to the planned volumes, and the mean difference in the width of the internal gap was 41 ± 9 µm. All printed results differed significantly from the planned inlays in terms of volume measurement (p < 0.001). There were no significant differences in terms of volume between the three print batches, nor the mean gap widths between teeth and restorations. The ICC for the volume precision measurement was 0.991. CONCLUSIONS:The amount of volume shrinkage that occurs during 3D printing is consistent. Adjusting the width of the spacer can compensate for the volume loss. CLINICAL RELEVANCE:Additively manufactured inlays undergo consistent volume shrinkage, which may impact their fit. Examining the distances between the planned and printed inlays revealed that there is a minimum offset at which the restorations could be inserted. The combination of material and 3D printer resulted in repeatable precise prints. The fit of indirect restorations can be predictably improved by coordinating intraoral scanners, 3D printers and printing materials.

Objectives: This monocentric cohort study was performed to investigate the relationship between periodontal and geriatric health parameters. Whether and to what extent periodontal health is related to geriatric indices has received little attention to date. Materials and Methods: The parameters of periodontal health were examined in 51 geriatric patients, while geriatric health was assessed using standardized evaluations, including Tinetti Test, Mini-Mental State Examination (MMSE), handgrip strength, and Barthel Index. Periodontal parameters included probing pocket depth (PPD), clinical attachment level (CAL), bleeding on probing (BOP) and approximal plaque index (API). Oral hygiene habits were evaluated using a structured questionnaire. Results: CAL was significantly associated with patients fall risk determined by Tinetti Test. An increase in CAL in one unit was associated with a corresponding decline in balance and gait (p < 0.05). BOP and API were significantly associated with Tinetti Test (p < 0.05). Increased handgrip strength was significantly associated with a decline of CAL (p < 0.05). A significant inverse correlation was found between API and MMSE (p < 0.05). The present study revealed no significant association between Barthel Index and periodontal parameters. Conclusions: The study suggests that the deterioration of periodontal health is associated with a decline in geriatric health, whist Tinetti Test appears to be a potentially effective assessment tool. Clinical Relevance: These findings may promote the development of targeted preventive strategies focused on the periodontal health requirements of this hospitalized patient group.

PURPOSE:This systematic review and meta-analysis evaluated the efficacy of natural ingredients used in toothpastes and gels in improving gingival health. MATERIALS AND METHODS:A comprehensive search strategy using different databases was conducted in accordance with PRISMA guidelines to identify randomized clinical trials (RCTs) on the use of natural ingredients for improving gingival health. Included studies focussed on outcomes measuring gingival health parameters, such as gingival index (GI), or bleeding on probing (BoP). Out of 249 identified studies, 10 RCTs met the inclusion criteria. Formulations included natural ingredients from plant extracts such as Aloe vera or Pudilan, and hydroxyapatite (as tooth-like calcium phosphate). RESULTS:The meta-analysis demonstrated a statistically significant improvement in gingival health when natural ingredients were used compared to control toothpastes and gels (p=0.0051). These findings suggest that natural ingredients may offer comparable or superior efficacy to conventional oral care products in terms of gingival health. Notably, Aloe vera and hydroxyapatite consistently demonstrated clinical benefits. CONCLUSIONS:Natural ingredients used in oral care products represent a promising strategy in gingivitis prevention and management. Their use in toothpastes and gels may therefore provide clinicians and patients with evidence-based, well-tolerated alternatives or adjuncts to conventional formulations for maintaining and improving gingival health.

Abstract This retrospective matched case-control study aimed to identify potential risk factors associated with the development of dental abscesses during or after endodontic treatment. The study analyzed data from 133 patients (74 males, 58 females; mean age 43.1 ± 16.5 years) with abscess formation of endodontic origin and compared them with a 1:1 matched control group without abscess. Matching was performed based on age and the specifically treated tooth. Collected variables included preoperative symptoms, radiographic findings, type and stage of endodontic intervention, and systemic medical conditions. Statistical analysis used chi-square or Fisher exact tests to compare between groups. STROBE and PROBE guidelines were followed. Among 2637 maxillofacial infections of odontogenic origin, 526 cases (19.9%) were related to endodontic treatment. No statistically significant associations were found regarding age, sex, or underlying systemic diseases (p > 0.05). Teeth exhibiting apical radiolucency were at significantly higher risk for abscess development (p < 0.001). Teeth that had undergone definitive root canal filling were significantly less likely to develop abscesses compared to those left without temporary filling after trepanation (p < 0.001) or treated with intracanal medication and temporary filling (p = 0.009). The highest incidence of abscess formation was observed within the first four days post-treatment (p < 0.001). Within the limitations of this retrospective study, abscess formation during or after endodontic treatment was linked to local procedural and radiographic factors, whereas systemic diseases did not demonstrate a measurable influence. The absence of temporary sealing and the presence of apical radiolucency were identified as significant risk indicators and may warrant increased clinical attention, particularly in the early postoperative period. Given the retrospective design and limited sample size, these findings should be interpreted with caution and require confirmation in prospective studies.

Purpose: The aging population presents an increasing demand for healthcare, including dental care. Oral health in older adults is often compromised by physical limitations, chronic diseases, and medications. This study investigates the oral health status of geriatric patients and its correlation with general medical, psychosocial, and functional health indicators. Materials and Methods: A cross-sectional observational study was conducted from January 2022 to September 2023, involving 62 hospitalized patients (aged 69-99) in a geriatric unit. Dental health was assessed using the DMFT index, and geriatric assessments included the Barthel Index, Tinetti mobility test, and hand strength measurements. Participants' demographic and clinical data, such as marital status, living situation, and care level, were recorded. Descriptive and inferential statistical methods were used for data analysis. Results: A statistically significant association was observed between the level of geriatric impairment and oral health status, as assessed by the DMFT index, in older patients. Cognitive function, measured by the Mini-Mental State Examination (MMSE), showed a strong relationship with oral health. Participants with severe dementia had a statistically significantly higher DMFT index (p <0.001) and a greater number of missing teeth (p <0.001) compared to those without cognitive impairment. Mild cognitive impairment was associated with an increased number of decayed teeth (p = 0.044), while severe dementia was linked to a statistically significant rise in the number of decayed teeth (p < 0.001). Physical function, as assessed by the Barthel Index, was also statistically significantly associated with oral health. The DMFT index was higher among participants with mild (p = 0.007) and severe dependency (p = 0.033) compared to independent individuals. The number of missing teeth was statistically significantly greater in participants with mild (p < 0.001), moderate (p = 0.049), and severe dependency (p = 0.013). Furthermore, those who were totally dependent had a statistically significantly higher number of decayed teeth (p = 0.039). Conclusion: Oral health is crucial to overall health and quality of life in the elderly. Integrating dental assessments into geriatric care is essential, and tailored dental treatment strategies are needed to improve the well-being of geriatric patients. Future research should explore causal relationships between oral health and geriatric diseases to refine care strategies.

Periodontitis is a chronic inflammatory disease characterised by progressive destruction of the periodontal tissues and alveolar bone. Cyclooxygenase-2 (COX-2) plays a key role in the pathogenesis of inflammatory responses via prostaglandin E2 (PGE2) receptors (EP1-4). Non-invasive physical plasma (NIPP) has been shown to modulate cellular activity and exert antimicrobial and anti-inflammatory effects. The aim of this in vitro study was to investigate the impact of NIPP on inflammation- and apoptosis-related molecules, including COX-2, EP2-EP4, Interleukin (IL)-6, IL-8, apoptotic protease activating factor 1 (APAF-1), Caspase (CASP)-3, and CASP-9, IL-10 and B-cell lymphoma 2 (BCL2) in human periodontal ligament cells (hPDLC) under normal and inflammatory conditions. After exposure of hPDLC to IL-1β to mimic inflammation in vitro, cells were treated with NIPP. Gene expression was analysed 24 h post-treatment by quantitative RT-PCR. Protein levels were assessed by ELISA. NIPP significantly inhibited IL-1β-induced upregulation of COX-2, EP2 and EP4 receptors, and APAF-1 mRNA expression in hPDLCs after 24 h. At the protein level, IL-1β-induced expression of COX-2, IL-6 and IL-8 was effectively attenuated by NIPP treatment. In conclusion, our data suggest that NIPP may modulate inflammatory responses in hPDLC, indicating its potential as a promising adjunctive approach for the treatment of periodontitis.

Background:Periodontitis is a widespread disease with high global prevalence. Alongside medical consultations, patients and healthcare professionals increasingly seek diagnostic and treatment information online. However, few studies have analyzed these search queries, despite their potential to reflect public interest and concerns. Extracting and analyzing such queries may contribute significantly to personalized diagnostics, therapy, and prevention, while also raising awareness of the disease. Methods:The web tool Google Trends and its extension Glimpse were used to identify and analyze the relative and absolute search volumes of "periodontitis" and "gingivitis", along with related queries, in five countries (Germany, Italy, France, Spain, and the USA) for the years 2008-2025. Additionally, Ubersuggest provided data on search volumes, device types, age groups, and click behavior. Statistical analysis was conducted using GraphPad Prism Software and included linear regression, distribution analysis and comparison as well as Chi-squared tests. Results:From 2008 to 2025, search volumes for both terms increased significantly in all five countries. In Germany and Italy, "periodontitis" overtook "gingivitis", while in France, Spain, and the US, "gingivitis" remained more frequently searched. Age-specific trends showed gingivitis queries peaked among 18-34-year-olds, while periodontitis was most searched by those aged 25-44. Most searches were conducted via mobile devices, especially in Italy and the USA. Around 50% of users did not click on any result, and organic results were preferred over advertisements. Related queries highlighted strong interest in treatment, home remedies, veterinary relevance, and-uniquely in Spain-celebrity connections. Conclusion:Search interest in gingivitis and periodontitis is high and has grown significantly from 2008 to 2025 across all examined countries. This suggests increased awareness but also reveals a need for improved education and accessible information. Frequently searched topics focused on etiology, diagnosis, and treatment, underscoring the role of search engines as key sources of medical information. These insights offer valuable, unfiltered reflections of patient concerns and questions. In an era of personalized medicine, such data should be integrated into patient-centered care strategies to better address individual needs.

This cross-sectional study investigated the association between periodontal status and geriatric health parameters, a relationship that has received little attention in research to date. The periodontal health of 51 geriatric patients was assessed based on probing pocket depth (PPD), clinical attachment level (CAL), bleeding on probing (BOP) and approximal plaque index (API). General health was evaluated using the Tinetti Test, Mini-Mental State Examination (MMSE), handgrip strength test and the Barthel Index. Oral hygiene habits were evaluated using a structured questionnaire. CAL was significantly associated with patients fall risk determined by Tinetti Test. An increase in CAL corresponded with a decline in balance and gait (p < 0.05). BOP and API were also significantly associated with Tinetti Test (p < 0.05). Moreover, a decrease in CAL was significantly associated with an increased handgrip strength (p < 0.05). A significant inverse correlation was also found between API and MMSE (p < 0.05). The present study revealed no significant association between Barthel Index and periodontal parameters. The study suggests that a decline in periodontal health is associated with a deterioration in general health in older age, with the Tinetti Test potentially serving as a valuable geriatric parameter. These findings may promote the development of targeted preventive strategies focused on the periodontal health requirements of this hospitalised patient group.

Background/Objectives: Deep subgingival proximal carious lesions present significant restorative and periodontal challenges, especially when approaching the supracrestal attachment (SA). This study compared two established deep margin elevation (DME) tecniques-the modified matrix technique (MMT) and the matrix-free "R2 technique" (R2T)-with respect to surface roughness, marginal adaptation, surface integrity, voids and excess adhesive material. Methods: Forty extracted human mandibular molars were prepared with standardized proximal cavities 2-3 mm below the cementoenamel junction (CEJ) and randomly assigned to two groups (n = 20 each). Group 1 received DME with the modified matrix technique; Group 2 was treated with the R2T. In both groups, a flowable bulk-fill composite was applied. Surface characteristics and marginal adaptation were evaluated using scanning electron microscopy (SEM) and laser profilometry. Qualitative scoring and quantitative measurements were performed. Statistical analysis was conducted using GraphPad Prism (version 10.02.0). Results: The modified matrix technique resulted in significantly smoother composite surfaces (p < 0.001), whereas the R2T showed significantly fewer voids, better marginal adaptation, and less excess bonding material (p < 0.05). No statistically significant difference was observed in surface integrity between the groups. Conclusions: While the MMT produced smoother surfaces, the R2T resulted in superior marginal quality with fewer voids and less excess adhesive material. The findings suggest technique-specific advantages rather than overall superiority, indicating that both approaches appear feasible. Clinical decision-making should be guided by anatomical and operator-related factors.

OBJECTIVES:To make the case, from periodontology and dental public health, for interdisciplinary action on oral and systemic health, and to set out recommendations for practice, policy, education, and research. MATERIALS AND METHODS:A joint working group of the European Federation of Periodontology (EFP) and the European Association of Dental Public Health (EADPH), with public-health stakeholders and delegates from organized medicine (the World Heart Federation, WONCA Europe and the European Forum for Primary Care), synthesized the epidemiological, mechanistic, preventive and health-systems evidence, and developed consensus recommendations. RESULTS:Oral diseases affect around 3.5 billion people and share modifiable risk factors (free sugars, tobacco, and alcohol) and social and commercial determinants with the major non-communicable diseases (NCDs); inadequate oral hygiene is an additional oral-specific factor. This argues for integrating oral health into general health through a common risk factor approach rather than disease silos. Periodontitis has the strongest evidence for systemic interactions and, unusually among oral diseases, its treatment improves glycemic control in diabetes and inflammatory or vascular surrogates, though evidence for major clinical events remains limited; other links rest largely on shared risk factors and mechanisms (an asymmetry of evidence, not of public-health importance). Prevention and integrated care remain under-implemented. CONCLUSIONS:Oral health must be recognized as integral to general health and embedded within NCD strategies and universal health coverage through interprofessional, intersectoral action that also tackles the social and commercial determinants and reduces inequalities. CLINICAL RELEVANCE:Equipping all health and social-care professionals to promote oral self-care, screen and refer, and prioritize periodontal prevention and treatment, can improve both oral and systemic outcomes.

Ghrelin signaling, mediated by the growth hormone secretagogue receptor (GHS-R1a), has emerged as an important regulator of inflammation and bone metabolism. This study investigated GHS-R1a regulation in periodontal tissues exposed to experimental periodontitis (EP), orthodontic tooth movement (OTM), or both. Human periodontal fibroblasts were stimulated with Fusobacterium nucleatum, static tensile strain, or their combination, and GHS-R1a expression was evaluated by RT-qPCR. In vivo experiments were conducted in rats subjected to EP, OTM, or combined treatment. Gingival GHS-R1a expression was assessed by RT-qPCR and immunohistochemistry, while alveolar bone loss was quantified histometrically. Combined bacterial and mechanical stimulation markedly increased GHS-R1a expression in periodontal fibroblasts, whereas either stimulus alone produced minimal changes. Similarly, combined EP and OTM induced a pronounced early increase in gingival GHS-R1a gene and protein expression, which declined over time. Animals exposed to both conditions also exhibited significantly greater alveolar bone loss. These findings demonstrate that periodontal inflammation and orthodontic loading dynamically regulate GHS-R1a, with early upregulation followed by attenuation during prolonged inflammation. The ghrelin/GHS-R1a system may therefore contribute to the periodontal response to concurrent inflammatory and biomechanical stimuli and participate in maintaining tissue homeostasis under inflammatory stress.

Mechanical forces, particularly tensile stress, influence tumor progression by modulating cancer-associated fibroblast (CAF) behaviour and extracellular matrix remodelling, yet their role in oral cancer remains insufficiently defined. To our knowledge, this is the first study investigating in vitro tensile stress responses in CAF and normal fibroblasts (NF) derived from oral squamous cell carcinoma (OSCC). To assess how tensile stress affects fibroblast gap closure, proliferation, metabolic activity, and paracrine signalling relevant to tumor-stroma interactions. CAFs and NFs were isolated from OSCC tissue and matched healthy mucosa and exposed to cyclic tensile strain (3

AIM:To evaluate the efficacy of a digital health companion app as an adjunct to systematic periodontal therapy. METHODS:Seven German university dental centres conducted this multi-centre randomised controlled trial. Adults with periodontitis (n = 194) were assigned to standard periodontal care with or without the Paro-ComPas app. The primary endpoint was the gingival bleeding index (GBI) at baseline, re-evaluation and during supportive periodontal care. Secondary outcomes included plaque and bleeding on probing. Confirmatory analyses used longitudinal mixed-effects regression. Exploratory analyses examined clinical outcomes by app usage cluster. RESULTS:Of the 180 participants, 148 completed the trial. Both groups showed substantial clinical improvements. The unadjusted between-group difference favoured the control group [7.70 pp (0.55; 14.85) at T0-T2]; the adjusted analysis showed no significant difference in the primary endpoint (1.56 pp; p = 0.352) or in secondary endpoints. Implementation fidelity was suboptimal. Exploratory analyses revealed that moderate app users achieved significantly greater plaque reductions compared to low users (-14.95 pp; p = 0.034). CONCLUSIONS:This trial found no significant benefit of a digital companion app as an adjunct to systematic periodontal therapy. Low baseline inflammation, incomplete intervention delivery and inter-examiner variability likely limited detection of small effects. Exploratory findings suggest potential benefits among moderately engaged users. TRIAL REGISTRATION:The study was registered in an international trial register (German Clinical Trial Register number DRKS00031263, registration date 19/06/2023, https://www.drks.de/search/de/trial/DRKS00031263/details).

Background/Objectives: Fine motor skills are essential for procedural precision in dental education. This study evaluated preparation performance and self-assessed skills among students completing either a dental technology and materials science-based curriculum (DTMS) or a shorter prevention-oriented curriculum (PREV). Assessments were conducted before and after a shared preclinical simulation course. We hypothesized that DTMS students would perform better at baseline and that differences would diminish after the course. Methods: Students in the DTMS and PREV groups prepared a standardized practice block at the beginning and end of a 14-week shared simulation course. Preparations were evaluated for depth, form, and surface smoothness. Students also completed a self-assessment questionnaire using a five-point Likert scale. Results: Sixty-four students participated (68.8% female). At baseline, the PREV group (PREVG) achieved significantly higher overall scores (p = 0.036) and better adherence to preparation form (p = 0.011) than the DTMS group (DTMSG). Following the simulation course, the PREVG showed significant improvements in overall scores (p = 0.009), preparation form (p < 0.001), and surface smoothness (p < 0.001), accompanied by improved self-assessed preparation skills (p = 0.006). In contrast, the DTMSG showed no significant changes in overall scores or individual quality parameters (p > 0.05). Conclusions: A prevention-oriented preclinical curriculum focusing on structured dental procedures was not inferior to a more extensive materials science-based curriculum despite fewer practical exercises. Continuous practice remains essential, while reduced practical workloads may provide curricular capacity for modern interdisciplinary teaching.

OBJECTIVE:To evaluate salivary apelin levels in individuals with and without type 1 diabetes presenting an intact periodontium and varying degrees of plaque-induced gingival inflammation. METHODS:Saliva samples were collected; and whole-mouth clinical periodontal measurements were recorded in type 1 diabetes and systemically healthy participants. Salivary apelin concentrations were determined using ELISA. Data were analysed statistically using the Shapiro-Wilk test for normality of distribution, the Mann-Whitney U test for intergroup differences, and Spearman's rank correlation analysis to assess correlations between clinical and biochemical parameters. RESULTS:A total of 99 participants; including 59 individuals in the type 1 diabetes group and 40 in the systemically healthy were included. The two groups were similar in terms of age, gender distribution, and smoking status (p > 0.05). The salivary apelin concentration in the diabetic group (4647.13 ± 8584.45 pg/mL) was almost twice that in the systemically healthy group (2704.12 ± 3006.73 pg/mL) without statistically significant difference (0.114). Clinical periodontal measurements were similar between the two groups (p > 0.05). Neither gender nor smoking status had a significant effect on apelin levels (p > 0.05). CONCLUSIONS:Within the limitations of this study, the observed trend toward higher salivary apelin levels in patients with type 1 diabetes may suggest a possible association that requires confirmation in larger cohorts.

Abstract Langerhans cells (LC) are specialized antigen-presenting cells that form a dense immune surveillance network within the oral epithelium. There, they continuously interact with epithelial cells and the resident microbiota to maintain mucosal homeostasis. A defining feature of LC is their highly dendritic morphology, which enables efficient sampling of the environment at barrier surfaces. Although E-cadherin–mediated adhesion has been implicated in LC–epithelial cell interactions, its role in oral LC biology and periodontal immune homeostasis remains elusive. Here, we investigated the function of E-cadherin on oral LC using CD11c-specific E-cadherin–deficient (CD11c-Ecad DEL ) mice. Loss of E-cadherin profoundly altered LC morphology throughout the oral mucosa, resulting in reduced dendrite formation and impaired dendrite extension towards the epithelial surface, thereby disrupting interaction with the oral microbiota. While the total number of LC remained unchanged, E-cadherin deficiency significantly altered the relative distribution of LC subsets, characterized by reduced LC1 and increased LC2 populations. E-cadherin–deficiency was associated with pronounced oral dysbiosis, characterized by increased bacterial burden and microbial diversity, as well as a shift away from the commensal-dominated community, particularly through the loss of protective lactobacilli. Transcriptome analysis of gingival tissue revealed inflammatory reprogramming marked by enrichment of NF-κB, TNF, IL-17, Toll-like receptor, and MAPK signaling pathways. Consistently, CD11c-Ecad DEL mice exhibited increased IL-17A production in the gingiva, expansion of αβ and γδ T cells, spontaneous age-dependent alveolar bone loss, and exacerbated inflammatory bone destruction in a model of ligature-induced periodontitis. In summary, our findings reveal that E-cadherin preserves oral LC dendrite organization and microbiota-dependent immune homeostasis, thereby limiting dysbiosis-driven inflammation and periodontal bone loss.

Background: Periodontitis is a chronic inflammatory disease that leads to tooth loosening and ultimately tooth loss. Regenerative approaches employing bioactive substances aim to restore lost tissues. Platelet-rich fibrin (PRF) is a simple and cost-effective option, but its effects on periodontal ligament (PDL) cells under inflammatory conditions remain unclear. Objectives: This study investigated the stimulating effects of platelet-rich fibrin on molecules crucial for periodontal wound healing and tissue remodelling in periodontal ligament (PDL) cells, under normal and inflammatory conditions mimicked by TNF-α. Methods The stimulating effects of different concentrations of PRF on the gene expression of VEGF, BMP2, COX2, TNF-α, and SPP1 were analysed by real-time PCR and ELISA. In addition, the possible modulating effects of TNF-α, a pro-inflammatory cytokine associated with periodontitis, on PRF-induced effects were studied. Furthermore, cell viability, proliferation, and migration were investigated. Results: A 2–3-fold dose-dependent increase in the expression of all the aforementioned genes by PRF was observed at 24 h and 48 h. Additional incubation with TNF-α did not lead to any significant modulation of PRF-induced expression patterns, indicating that the effects of PRF were not compromised in an inflammatory environment. Functionally, PRF caused a significant 35% increase in cell migration between 24 h and 48 h, which was again not affected by a pro-inflammatory condition. Cell viability and proliferation remained largely unaffected by PRF, irrespective of the presence of TNF-α or not. Conclusions: The results suggest that PRF can promote initial periodontal wound healing even in an inflammatory environment by stimulating the expression of cytokines, growth factors and markers of osteogenic differentiation such as VEGF, BMP2 and SPP1, which are involved in angiogenesis, tissue remodelling, and/or cell migration.

Background/Objectives: Periodontal disease involves chronic immunoinflammatory processes and microbial dysbiosis, making phytochemicals with anti-inflammatory properties potential therapeutic agents. This study aimed to assess the modulatory effects of yellow passion fruit bagasse extract (PFBE) on periodontal cells under microbial condition. Methods: A human periodontal ligament (PDL) cell line was exposed to F. nucleatum ATCC 25586 to simulate a microbial environment in vitro in the presence and absence of PFBE containing three different concentrations (0.25, 0.50, and 1.00 µg/mL) of piceatannol. Pro-inflammatory markers (TNF-α, IL-8, CCL2), the antioxidant enzyme SOD2, and the protease marker MMP-1 were analyzed by real-time PCR. Protein levels were assessed via ELISA and NF-κB nuclear translocation by immunofluorescence. Cell viability was investigated using live/dead and alamarBlue assays, and in vitro wound healing was evaluated by an automated scratch assay. Results: PDL cells exposed to F. nucleatum significantly increased the gene and protein expression of all inflammatory markers. The stimulatory effects of F. nucleatum were significantly reduced when PDL cells were simultaneously exposed to PFBE. F. nucleatum triggered the NF-κB nuclear translocation while PFBE abrogated the F. nucleatum-stimulated NF-κB nuclear translocation at 60 min. Viability assays demonstrated that neither PFBE nor F. nucleatum were toxic or significantly affected PDL cell viability. In vitro wound closure was improved by the addition of PFBE to F. nucleatum. Conclusions: PFBE exhibited anti-inflammatory and anti-proteolytic effects while improving in vitro wound healing, suggesting a potential modulatory role of PFBE in periodontal disease prevention and treatment.

The intra- and intercellular signaling molecule nitric oxide (NO) is produced in endothelial cells by the activity of endothelial NO synthase (eNOS). Upon formation, NO diffuses into the underlying vascular smooth muscle cells, where it activates NO-sensitive guanylyl cyclase (NO-GC) resulting in the production of cyclic guanosine 3',5'-monophosphate (cGMP) from guanosine 5'-triphosphate (GTP). Inducing vasodilatation, inhibiting platelet aggregation and leukocyte adhesion, and inhibiting the proliferation and migration of vascular smooth muscle cells, the NO-cGMP signaling leads to a number of anti-inflammatory processes. Inflammation-dependent elevated concentrations of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in blood vessels of inflamed dental pulp induce an uncoupling of eNOS and oxidized NO-GC, leading to a disruption of NO-cGMP signaling. Endothelial dysfunction in inflamed dental pulp alters cell-cell and cell-matrix interactions, reducing the regenerative and reparative potential of the dentin-pulp complex in response to carious lesions. In the therapeutic management of caries, it is essential to consider the presence of endothelial dysfunction in the inflamed dental pulp. The utilization of NO-GC stimulators and activators in indirect and direct pulp capping materials may enhance the regeneration and repair potential of inflamed dental pulp.