PURPOSE:Optimized surface properties are a pivotal factor for dental ceramic implants and overall implant success. After grit-blasting and spray-coating Aluminum Toughened Zirconia (ATZ) ceramic samples with a glass solder, the biological cell response was examined and compared to uncoated and solely grit-blasted samples of the same ceramic. METHODS:In this study, a silica-based glass solder was evaluated for cytocompatibility, osteogenic differentiation, and hemocompatibility using L929 mouse fibroblasts and human dental pulp cells (HDPCs). RESULTS:No toxic effects were observed for either coated or uncoated ATZ samples in direct or indirect tests, as assessed by live/dead staining. Differentiation and viability assays with HDPCs and L929 mouse fibroblasts showed no toxicity, and osteogenic differentiation was not impaired by the coating. Hemocompatibility testing with human whole blood revealed similar results for coated and uncoated ceramic specimens, with no hemolysis or adverse effects on standard hematological parameters. CONCLUSIONS:The glass solder coating was cytocompatible and hemocompatible under the tested in vitro conditions and did not impede osteogenic differentiation. These findings indicate that it can serve as a suitable substrate for the proliferation and spreading of L929 fibroblasts and HDPCs, with potential benefits for improving dental ceramic implant surfaces.

The lymph node management of oral squamous cell carcinoma (OSCC) patients with pN1 neck remains a clinical challenge. This study investigates the impact of different treatment modalities – surgery alone, surgery with postoperative radiotherapy (PORT), and surgery with postoperative chemoradiotherapy (PCRT) – on recurrence and survival outcomes in OSCC patients with pN1 neck. A retrospective cohort study was conducted on 98 patients who underwent tumor resection and neck dissection, with a subset receiving adjuvant therapy, between 2011 and 2020. Clinicopathological characteristics were examined for associations with treatment modality using chi-square test. Kaplan-Meier survival curves for overall survival (OS) and recurrence-free survival (RFS), along with the log-rank test, were employed to assess survival over a 10-year period. The prognostic significance of clinicopathological factors and treatment modalities was evaluated using Cox proportional hazards models. The addition of PORT following surgery significantly reduced the risk of recurrence (HR = 0.280, p = 0.010) and enhanced RFS, particularly at 10 years (p = 0.010). PORT was also associated with a statistically significant improvement in 5-year-OS (p = 0.031) compared to surgery alone, with a trend toward improved OS at 10 years (p = 0.175). In contrast, surgery alone did not yield comparable 10-year survival outcomes. Additionally, the inclusion of PCRT did not show a distinct survival advantage over the combination of surgery and PORT. Our results indicate that PORT may be considered the standard adjuvant treatment for these patients, as it improves RFS, particularly in the long term, while the addition of chemotherapy does not provide significant additional benefits over PORT alone.

Raman Difference spectroscopy (RDS) presents a promising, non-invasive approach for facilitating rapid diagnosis of oral squamous cell carcinoma (OSCC). Many ex vivo studies rely on formalin-embedded tissue specimens. Spectroscopic changes and classification of formalin-fixed OSCC tissues were investigated. In an analysis of 47 specimens (n = 30 OSCC, n = 17 physiological mucosa), RDS was employed at 180 distinct measurement loci after storage in saline, and again at 125 measurement loci after storage in formalin. For classification, Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA) were utilized. In distinguishing OSCC from physiological mucosa, LDA revealed a higher sensitivity (97.6% for NaCl-stored vs. 90.9% for formalin-fixed tissues), specificity (93.0% vs. 78.6%), and overall classification accuracy (95.2% vs. 85.4%) for specimens stored in saline. While formalin fixation is valuable for tissue preservation in histopathology, Raman spectra of OSCC tissues were substantially altered, with implications for validation of innovative optical techniques such as Raman Spectroscopy.

Distant metastases (DMs) are a significant prognostic factor in oral squamous cell carcinoma (OSCC). This study analyzed the pattern and predictors of metachronous DMs (MDMs) over time in a large OSCC cohort treated with curative intent. A total of 1,122 patients with primary OSCC were treated at the University Medical Center Hamburg-Eppendorf between 2009 and 2019. After excluding patients with synchronous metastases or palliative treatment, 1,040 patients remained for analysis. Of these, 93 patients (8.94

Biodegradable biomaterials are promising candidates for regenerative wound care, yet their performance under infection-driven conditions remains poorly understood. This study evaluated the regenerative efficacy and structural persistence of a silk fibroin membrane and electrospun nonwoven matrix using a human ex vivo full-thickness skin wound model under non-infected and bacterially infected conditions. Complementary in vitro degradation assays assessed matrix durability following exposure to Staphylococcus aureus, Pseudomonas aeruginosa, bacterial culture supernatants and clinically relevant antiseptic solutions. In non-infected wound conditions, both matrices enhanced wound regeneration, resulting in increased re-epithelialization and proliferative activity compared with untreated controls; membrane-treated wounds achieved approximately 95% re-epithelialization after 15 days compared with approximately 20% in untreated controls, indicating accelerated wound closure, whereas nonwoven matrices supported sustained cellular proliferation over time. In contrast, bacterial infection was associated with almost complete absence of re-epithelialization and proliferative activity irrespective of matrix architecture. Matrix persistence was pathogen-dependent. While S. aureus induced moderate degradation, P. aeruginosa caused pronounced structural deterioration in ex vivo and in vitro models. Exposure to P. aeruginosa culture supernatants produced similar effects. These findings demonstrate that regenerative efficacy and material persistence are distinct biomaterial properties that are strongly influenced by the wound microbiological environment and are profoundly compromised under conditions of high bacterial burden.

OBJECTIVES:Postoperative complications remain a major challenge in the surgical management of oral squamous cell carcinoma (OSCC), particularly in the context of extensive resections and microvascular reconstruction. While comorbidity indices are commonly used for risk stratification, their predictive value relative to functional and procedural factors remains uncertain. MATERIALS AND METHODS:This retrospective cohort study included 401 consecutive patients undergoing curative-intent surgery for OSCC between 2017 and 2024. Postoperative complications within 30 days were graded according to the Clavien-Dindo classification. Preoperative comorbidity was assessed using the Charlson Comorbidity Index (CCI), Adult Comorbidity Evaluation-27 (ACE-27), Elixhauser Comorbidity Index (ECI), and the van Walraven-weighted ECI. Uni- and multivariate logistic regression analyses were performed to identify predictors of overall and major complications (Clavien-Dindo ≥ IIIb). RESULTS:Overall complications occurred in 73.1% of patients, with major complications in 28.4%. Operative duration ≥ 5.5 h was the strongest independent predictor of overall (OR 10.82; p < 0.001) and major complications (OR 2.20; p = 0.030). Impaired preoperative performance status (ECOG ≥ 1) independently predicted major complications (OR 1.50; p = 0.027). Among comorbidity indices, only the ECI was associated with overall complications (OR 1.48; p = 0.026), while all indices showed poor discrimination (AUC 0.52-0.59). In exploratory survival analyses, postoperative complications were associated with reduced overall survival in unadjusted Kaplan-Meier estimates but not in multivariable Cox regression. CONCLUSIONS:Procedural complexity and functional status outweigh traditional comorbidity indices in predicting postoperative morbidity after OSCC surgery. These findings support a shift toward perioperative risk assessment models that prioritize operative burden and physiological reserve over static comorbidity burden.

INTRODUCTION:The mechanism underlying the relationship between Alzheimer's disease (AD) and minerals (serum calcium, copper, iron, magnesium, zinc), vitamins (25-OH vitamin D, vitamin A1 [retinol], B9 [folic acid], B12, C) is unclear. METHODS:In a two-step Mendelian randomization analysis, the association between positive nutritional elements and 3935 magnetic resonance images (MRI) phenotypes was examined, and the mediation proportion was calculated. Horizontal pleiotropy and heterogeneity of MR were assessed using MR-Egger, Cochran's Q test, MR-PRESSO. RESULTS: 25-OH vitamin D (P = 0.0019, OR = 0.6179, 95% CI = 0.4562-0.8368, inverse weighted variance [IVW]) is negatively associated with AD among 10 nutrients. The mediation proportion of the effect of vitamin D on AD mediated by IDP_dMRI_TBSS_L3_Superior_fronto-occipital_fasciculus_L was ∼7.08%. DISCUSSION:Our results support 25-OH vitamin D as a causal protective factor for Alzheimer disease. It was found that the Superior_fronto-occipital_fasciculus_L may play a minimal mediating role.

Abstract Aim The aim of this study was to investigate the influence of overweight (BMI ≥ 25 (kg/m²)) on the oral health status in patients with adult hypophosphatasia (HPP). Materials and methods Throughout a retrospective assessment both oral health status and bone metabolism including dual x-ray absorptiometry (DXA) for bone mineral density (BMD) measures were analyzed. The oral health status was assessed by the decayed/missing/filled teeth index (DMFT), clinical attachment level (CAL), probing pocket depth (PPD), and the periodontal screening index (PSI). The study population was divided into two groups based on the overweight classification by BMI (Overweight = BMI ≥ 25 kg/m²; n = 17) vs. non-overweight ( BMI < 25 kg/m²; n = 31). Results 48 HPP patients were included in this study. Overweight HPP patients showed a significantly reduced oral health status regarding filled teeth, DMFT, PSI, PPD and periodontitis severity index compared to non-overweight HPP patients. Furthermore, overweight HPP patients revealed significantly higher DXA findings regarding BMD, T- and Z-scores. Conclusion In the present study overweight (BMI ≥ 25 (kg/m²)) is associated with a poorer oral health status and higher BMD in adult HPP. Clinical relevance Since overweight is associated with a poorer oral health status in the general population and promotes the development of periodontal disease, the findings of the present study indicate that overweight also affects oral health in adult HPP.

Background Stem cell-derived extracellular vesicles (EVs) hold great promise in regenerative medicine. However, a comprehensive understanding of the regenerative capabilities of EVs from different stem cell sources remains limited. Methods This study systematically compares EVs derived from three odontogenic cell types. Analyses includes EV isolation and characterization, cell viability assays, vasculogenesis experiments, proteomic profiling, and miRNA sequencing. Results All three EV types displayed similar surface marker profiles. Dental pulp stem cell-derived EVs showed superior cellular uptake, promoted higher cell proliferation, and enhanced vasculogenesis compared to periodontal ligament stem cell-derived EVs. Gingival fibroblast-derived EVs performed similarly in functional assays. Principal component analysis of miRNA profiles revealed strong biological heterogeneity among EV sources, with donor-specific factors exerting a greater influence on EV characteristics than cellular origin—an aspect underexplored in prior studies. Conclusions These findings underscore the complexity of EV functionality and highlight the regenerative potential of dental stem cell-derived EVs. ### Competing Interest Statement The authors have declared no competing interest. * α-MEM : Alpha Minimum Essential Medium BCA : Bicinchoninic Acid Assay CM : Conditioned medium DPSC : Dental pulp stem cell EGM-2 : Endothelial Cell Growth Medium 2 EVs : Extracellular vesicles FBS : Fetal bovine serum GO : Gene Ontology GF : Gingival fibroblast HUVECs : Human Umbilical Vein Endothelial Cells IFCM : Imaging Flow Cytometry KEGG : Kyoto Encyclopedia of Genes and Genomes MSC : Mesenchymal stromal/stem cell NTA : Nanoparticle tracking analysis PBS : Phosphate-buffered saline PCA : Principal Component Analysis PDLSC : Periodontal ligament stem cell TEM : Transmission electron microscopy Deutsche Forschungsgemeinschaft, 516860159

In the field of biomedical implants, additively manufactured titanium alloys, particularly Ti-6Al-4V, hold significant potential due to their biocompatibility and mechanical properties. This study focuses on the characterization and modeling of additively manufactured Ti-6Al-4V alloy for dental and maxillofacial implants, emphasizing fatigue behavior, surface modification, and their combined effects on cyto- and osseocompatibility. Experimental methods, including tensile, compression, and fatigue testing, were applied alongside in silico simulations to assess the long-term mechanical performance of the material. Surface properties were further modified through sandblasting and coating techniques to enhance cell adhesion and proliferation. By using in-vitro methods, the cytocompatibility of the coatings and materials was examined followed by in-vivo tests to determine osseocompatibility. Results demonstrated that appropriate surface roughness and modifications are essential in optimizing osseointegration, while the layer-by-layer additive manufacturing process influenced the fatigue life and stability. These findings contribute to the development of patient-specific implants, optimizing both mechanical integrity and biological integration for enhanced clinical outcomes. This work summarizes the investigations on additively manufactured Ti-6Al-4V alloy of the research unit 5250 “Mechanism-based characterization and modeling of permanent and bioresorbable implants with tailored functionality based on innovative in vivo, in vitro and in silico methods” funded by the Germany Research Foundation (DFG).

Silk fibroin (SF) is a biomaterial derived from the cocoon of the mulberry silkworm. This study aimed to assess the capacity of SF matrices biologized with injectable platelet-rich fibrin (iPRF) or enamel matrix protein (EMP) to modulate angiogenesis and immune response in the chorioallantoic membrane (CAM) assay. 300 eggs were divided into the following groups: CM + NaCl, CM + iPRF, CM + EMP, SF + NaCl, SF + iPRF, and SF + EMP. Matrices were applied to the CAM on embryonic development day (EDD) 7 after rehydration. Angiogenesis, represented by vascularized area, vessel density, and vessel junctions, was evaluated on EDD 10, 12, and 14. Additionally, gene expression of HIF-1ɑ, VEGF, MMP-13, and NOS2 was assessed via quantitative polymerase chain reaction (qPCR) on EDD 11 and 14. The number of vascularized specimens was notably higher in SF matrices regardless of the treatment applied, while in the CM group, only matrices biofunctionalized with iPRF demonstrated vascularization. On EDD 14, the CM + iPRF group exhibited the highest values for total vascularized area (CM + iPRF: 57.52

BACKGROUND:Radiation-induced sarcomas (RIS) are rare entities that have been studied infrequently in large cohorts, with most data derived from case reports or small series. This study aims to systematically evaluate existing data to synthesize and consolidate current knowledge. METHODS:An electronic literature search was conducted using PubMed and the Cochrane Library. The search included studies and case reports with clinico-histopathological and survival data on craniofacial RIS. RESULTS:Among 1237 studies identified, 143 studies with 701 patients were included. The average patient age was 48 years, with men nearly twice as likely to develop RIS. RIS had an average latency period of 12 years, with an average radiation dose of 63 Gy. Radiation-induced osteosarcomas (42.1 %) were most common, followed by fibrosarcomas (21.1 %). Nasopharyngeal carcinoma (53.0 %) and retinoblastoma (10.3 %) were the most prevalent primary tumors. 5.4 % of patients received radiotherapy for benign disease. The average latency period in this group was approximately 1.5 times longer than that observed in the group with malignancies; however, the average radiation dose was also approximately 15 Gy lower. Local recurrences occurred after an average of 16 months. The 1-, 2-, and 5-year survival rates were 67.8 %, 47.1 %, and 25.0 %, respectively. Surgical therapy showed the best survival rates (33.3 % after 5 years) while isolated chemotherapy yielded the lowest (0.0 %). CONCLUSION:The prognosis for craniofacial RIS remains poor despite aggressive treatment. Surgical intervention is the primary therapeutic approach, but optimal treatment regimens and the role of (neo-)adjuvant therapies require further investigation. This study underscores the complexity of managing RIS and highlights the need for ongoing research to improve outcomes.

Sentinel lymph node biopsy (SLNB) is a well-established method for managing primary oral squamous cell carcinoma (OSCC), but its role in recurrent or secondary carcinomas, particularly following previous neck dissection, remains insufficiently studied. This study explores the utility of SLNB in these challenging cases, focusing on reliability, sentinel lymph node (SLN) localisation trends, and clinicopathological factors, comparing results between primary and secondary/recurrent carcinomas. A retrospective analysis was conducted on patients with primary and recurrent or secondary OSCCs treated at a German tertiary medical centre. Chi squared tests were used to analyse correlations between clinicopathological characteristics and SLN localisation. The negative predictive value (NPV) was calculated, and the timing of recurrence was also evaluated. We found an NPV of 93.75% for SLNB in primary carcinomas, whereas it was 88.89% for secondary and recurrent carcinomas. While most SLNs were localised ipsilaterally across both groups, recurrent/secondary cancers showed a higher prevalence of contralateral SLNs (22.2%) and bilateral localisation patterns (11.1%) compared to primary carcinomas (8.3% contralateral; 8.3% bilateral). Despite observed trends, no statistically significant associations were found between SLN localisation and clinicopathological factors. The mean (SD) time to recurrence was significantly shorter for primary carcinomas with 9.20 (3.49) months compared to recurrent or secondary cases 32.00 (8.54) months). SLNB in recurrent or secondary OSCC shows distinct SLN localisation patterns, including more contralateral and mixed foci. In terms of NPV, SLNB is reliable in both primary and secondary/recurrent OSCC. Furthermore, a longer recurrence time reinforces the potential of SLNB as a viable alternative to neck dissection in managing these complex cases.

BACKGROUND/AIM:Cavernous hemangiomas in children older than 2 years will unlikely resolute and therefore, frequently require treatment. The aim of the study was to comparatively evaluated the outcome of the sclerotherapy with polidocanol and the conventional pingyangmycin therapy for thick cavernous hemangiomas in the oral cavity in children. PATIENTS AND METHODS:We treated a total of 21 cavernous hemangiomas in the oral cavity (majority on the tongue) of children aged 2-11 years by means of a sclerotherapy using an anesthetic agent polidocanol under ultra-sound monitoring. RESULTS:Total regression of the tumors was achieved in 20 cases, corresponding to a success rate of 95%, significantly (p=0.0005) higher than that achieved by the conventional pingyangmycin therapy, which was <50%. No severe complication was observed, while mild and transit ones such as local swelling, pain, and ulceration were reported by both groups at similar frequency (10-20%). CONCLUSION:Sclerotherapy using polidocanol provides an effective, safe, and relatively simple treatment for hemangiomas in the oral cavity of children and may be recommended to replace the conventional pingyangmicine treatment.

BACKGROUND/AIM:Head and neck cancer (HNC) is the sixth most common type of cancer worldwide. While it is widely accepted that human papillomavirus (HPV) infection is a crucial risk factor for the development of this type of cancer, there is still a lack of support from large-scale studies. This article addresses this gap by comprehensively analyzing the causal relationship between HPV infection and head and neck cancer using Mendelian randomization methods. PATIENTS AND METHODS:The HPV database was utilized to identify instrumental variables via the most enormous GWAS database search tool. The study examined five cancer groups of data of interest from the UK Biobank and three groups of cancer data from the GAME-ON network, all obtained from public databases. The causal relationship was estimated using various approaches, including IVW, weighted median, MR-Egger, simple mode, and weighted mode. RESULTS:The results indicated no causal relationship between HPV16/18 E7 proteins and head and neck cancer, oral cancer, oropharyngeal cancer, and laryngeal cancer, including UKB database and GEME-ON network. Furthermore, there was no heterogeneity or horizontal pleiotropy in the data. CONCLUSION:The analysis does not support a causal relationship between HPV infection and HNC, as indicated by the lack of evidence linking HPV16/18 E7 proteins to the development of this cancer.

BACKGROUND/AIM:Periodontal diseases and edentulism remain a prevalent and disabling oral health condition worldwide, with significant regional disparities. This study systematically evaluated the burden of periodontal disease and edentulism at global, regional, and national levels from 1990 to 2021, using the Global Burden of Disease (GBD) 2021 framework. PATIENTS AND METHODS:We analyzed trends in incidence, prevalence, and years lived with disability (YLD), exploring their associations with the socio-demographic index (SDI) and other risk factors. RESULTS:The findings reveal considerable variations across SDI regions, with low and low-middle SDI regions experiencing the highest burden. In 2021, the global prevalence of periodontal diseases reached approximately 1.07 billion cases, and the age-standardized incidence and prevalence rates varied significantly by SDI levels. The burden of periodontal disease showed an increasing trend among middle-aged and elderly populations. While sex differences were present in both edentulism and periodontal diseases, they were relatively minor. ARIMA model projections indicate that the burden of edentulism will fluctuate by 2050, while the burden of periodontal diseases will remain stable. CONCLUSION:This study underscores the need for targeted public health interventions, particularly in resource-limited regions, to improve access to oral healthcare and integrate preventive strategies into broader health initiatives.

Peri-implantitis is known as an inflammatory condition affecting the soft and hard tissue around dental implants. A promising strategy to prevent these conditions is the use of antibacterial implants. This study aimed to evaluate the antibacterial potential of titanium (Ti) dental implants modified using plasma-electrolytic oxidation (PEO). The modified surfaces were subsequently loaded with silver (Ag) ( n = 6) and zinc (Zn) ( n = 6) ions and compared to unloaded Ti specimens ( n = 6), with untreated specimens serving as controls. The specimens (each n = 5) were incubated in a culture medium containing a mixture of specific anaerobic bacterial strains. Scanning electron microscopy (SEM) was used to visualize the bacterial biofilm on each specimen. In addition, total bacterial deoxxyribonucleic acid (DNA) and the number of viable bacteria were determined using quantitative real-time polymerase chain reaction (qrt-PCR) and colony forming unit analysis (CFU), respectively. The results of the CFU analysis showed a 2 log (99%) reduction in viable bacteria in the samples loaded with Ag and Zn compared to the unloaded control group (p < 0.05). Moreover, significantly lower bacterial DNA counts were detected with a 5 log reduction (99.999%) in the Ag and Zn samples compared to the positive control group (bacterial mixed culture solution, p < 0.05). Therefore, it was considered that Ag and Zn loaded Ti implants may be a promising addition to current approaches to enable advanced antibacterial dental implants. However, further studies should be conducted to evaluate the in vivo cytocompatibility of the developed specimens.

Einleitung: Ziel dieser Studie war es, den Einfluss von Übergewicht (BMI≥25 (kg/m²)) auf den Mundgesundheitsstatus bei PatientInnen mit adulter Hypophosphatasie (HPP) zu untersuchen.

AIM:Vitamin D deficiency is common in hypophosphatasia (HPP) patients. However, its impact on oral health is unclear. Therefore, the purpose of this study was to investigate the relationship between Vitamin D levels and oral health in adults with hypophosphatasia. MATERIALS AND METHODS:In this retrospective study, oral health and bone metabolism in HPP patients were examined. The Decayed/Missing/Filled Teeth (DMFT) index, clinical attachment level (CAL), probing pocket depth (PPD), and periodontal screening index (PSI) were among the metrics used to evaluate oral health. RESULTS:The average age of the 48 HPP patients in the study was 42.21 (±15.78) years. A mean Vitamin D level of 29 μg/L was used to divide the participants into two groups. Compared to patients with Vitamin D levels above 29 μg/L, those with levels below this threshold showed noticeably worse oral health, as evidenced by higher PSI, PPD, decayed tooth count, and periodontitis severity index. CONCLUSION:The results imply that adults with HPP who have low Vitamin D levels have worse oral health. To potentially improve oral health, it is crucial to diagnose and treat Vitamin D deficiency in HPP patients, as it is a known risk factor for periodontitis in the general population.