Lichen sclerosus of the oral mucosa: a hidden phenomenon.

Oral lichen sclerosus (OLS) represents a diagnostic challenge even for expert dermatologists due to its rarity and subtle clinical manifestations. Only few cases have been reported in literature to date. OLS typically presents with whitish macules in the oral cavity. Histopathological examination remains crucial for definitive diagnosis, with characteristic features including epithelial atrophy, subepithelial hyalinization, loss of elastic fibers, and lymphocytic infiltration. Management strategies vary depending on lesion size and symptomatic presentation, with topical or intralesional corticosteroids being the most commonly used treatment modalities. Long-term monitoring is recommended due to the potential for malignant transformation, although no cases have been reported to date. Greater awareness and understanding of OLS are essential for accurate diagnosis and effective management. Based on these findings, we recommend performing an accurate evaluation of the oral mucosa, especially when dealing with patients affected by genital or extragenital lichen sclerosus (LS). Moreover, we emphasize the importance of multidisciplinary collaboration between dermatologists and other specialists of oral disorders, such as dentists. This short review briefly summarizes available data on OLS, highlighting its diverse clinical presentations and diagnostic challenges. Despite its infrequent occurrence, OLS should be considered in the differential diagnosis of white macules in the oral cavity.

Atypical cellular neurothekeoma of the oral mucosa: A rare case report and literature review.

Cellular neurothekeoma (CN) is a benign dermal neoplasm that most often affects the head and neck region and rarely occurs in the oral mucosa. We report a rare case of CN with atypical features on the floor of the mouth and summarize the reported cases of oral CN in English-language literature. A 62-year-old woman presented with a 6-month history of a painless mass on the floor of the mouth. Histopathological analysis of the excised specimen revealed a proliferation of neoplastic cells with oval to spindle morphology arranged in a vaguely nested and multinodular architecture separated by scarce hyaline collagen within a predominantly myxoid-rich stroma. The tumor cells were positive for NSE, and CD63 (NKI/C3), and negative for S100 protein, CD34, and SMA. Thus, the final diagnosis was CN. In addition, we summarized all clinicopathological data on oral CNs reported in the English-language literature. Nineteen cases were reviewed. Among them, only one case affected the floor of the mouth of a young girl, in contrast to the present case that occurred in an elderly woman. CN is particularly rare in this location and may be a diagnostic challenge for oral pathologists due to its rarity and morphological similarity with other lesions.

Development of an Ex Vivo Functional Assay for Prediction of Irradiation Related Toxicity in Healthy Oral Mucosa Tissue.

Radiotherapy in the head-and-neck area is one of the main curative treatment options. However, this comes at the cost of varying levels of normal tissue toxicity, affecting up to 80% of patients. Mucositis can cause pain, weight loss and treatment delays, leading to worse outcomes and a decreased quality of life. Therefore, there is an urgent need for an approach to predicting normal mucosal responses in patients prior to treatment. We here describe an assay to detect irradiation responses in healthy oral mucosa tissue. Mucosa specimens from the oral cavity were obtained after surgical resection, cut into thin slices, irradiated and cultured for three days. Seven samples were irradiated with X-ray, and three additional samples were irradiated with both X-ray and protons. Healthy oral mucosa tissue slices maintained normal morphology and viability for three days. We measured a dose-dependent response to X-ray irradiation and compared X-ray and proton irradiation in the same mucosa sample using standardized automated image analysis. Furthermore, increased levels of inflammation-inducing factors-major drivers of mucositis development-could be detected after irradiation. This model can be utilized for investigating mechanistic aspects of mucositis development and can be developed into an assay to predict radiation-induced toxicity in normal mucosa.

Histogical changes in oral mucosa (gingiva) as a method for estimating post-mortem interval: A literature review.

Estimating the post-mortem interval (PMI) is an essential step in forensic investigations, particularly those involving homicides and unwitnessed deaths. However, traditional methods occasionally yield inconsistent estimates. Histological and molecular techniques are considered crucial in forensic pathology and are frequently employed to estimate the time interval of death. The gingiva is an oral mucosal tissue used to estimate PMI. This review aimed to examine the potential of histological methods to determine PMI using oral mucosal tissue, namely the gingiva, and to investigate changes that occur in oral mucosal tissue at different time intervals when compared with those in normal tissues. The oral mucosa comprises layers of stratified squamous epithelium and connective tissue. Similar to other body tissues, changes are known to occur in the gingiva after death, and these cellular and tissue changes should also be considered. Alterations in the gingiva include homogenisation, karyorrhexis, pyknosis, karyolysis, chromatin clumping, eosinophilia, collagen fibre degradation, and the loss of tissue architecture. Reviews collating the results of original trials have consistently reported how the oral mucosa is altered by autolysis and how such changes can be observed in histological tissue morphology after death. Histology is an acceptably accurate technique for estimating PMIs.

Human Papillomavirus in Oral Lichen Planus: Is There an Association? A Meta-Analysis.

Lichen planus (LP) is a chronic, recurrent mucocutaneous inflammatory disease with unclearly defined etiology, where a potential role of several viruses has been considered. This meta-analysis aimed to determine the potential association between HPV and oral LP based on case-control and cross-sectional study results. A systematic search was performed in PubMed, Web of Science (SCI), Google Scholar, and Scopus databases with the last update on 6 March 2024. Pooled data were analyzed by calculating odds ratios (OR) and 95% confidence intervals (CI) with the metafor package for R. A total of 13 studies on 541 cases and 413 controls were included in this meta-analysis. It covered eight countries: India, Iran, Turkey, Czech Republic, Hungary, Italy, Macedonia, and the UK. In seven papers, the differentiation into the erosive-atrophic type and non-erosive-atrophic type of OLP was utilized. HPV infection was associated with at least a two times higher risk for a person with HPV to have OLP, depending on whether original data or filled/trimmed data were used. The OR values were 3.54 [2.01, 6.24] and 2.10 [1.16, 3.82], respectively. This meta-analysis was performed to identify the association between HPV and OLP and revealed that HPV infection was associated with at least a high risk for a person with HPV to develop OLP.

Frequencies of micronuclei in buccal cells and their spatial distribution in a population living in proximity to coal mining areas in southern Brazil.

The extraction and burning of coal release genotoxic pollutants, and understanding the relationship between genetic damage and the spatial distribution of residences in coal-using regions is crucial. The study aimed to conduct a spatial analysis of genotoxic damage through the of micronuclei (MNs) number and their proximity to coal mining/burning in the largest coal exploration region in Brazil. In this study, the detection of genotoxic damage was performed using the MN assay in oral cells of residents exposed to coal mining activities. Spatial analysis was conducted using QGIS 3.28.10 based on information obtained from a questionnaire administered to the population. Multiple linear regression analysis was carried out to assess the influence of the distance from residential areas to polluting sources on the number of MNs found. Additionally, Spearman's correlation was performed to identify the strength and direction of the association between the frequency of MNs and each of the polluting sources. A total of 147 MNs were quantified among all participants in the coal mining region. Notably, residents living within 2 km and 10 km of pollution sources exhibited the highest prevalence of MNs. The analysis demonstrated a significant correlation between closer proximity to pollution sources and increased MN frequency, underscoring the spatial relationship between these sources and genotoxic damage. Environmental pollutants from anthropogenic sources present a major health risk, potentially leading to irreversible damage. The spatial analysis in this study highlights the importance of targeted public policies. These policies should aim for a sustainable balance between economic development and public health, promoting effective measures to mitigate environmental impacts and protect community health.

MASCC/ISOO Clinical Practice Statement: Management of oral manifestations of chronic graft-versus-host-disease.

PURPOSE: A MASCC/ISOO Clinical Practice Statement (CPS) is aimed at generating a concise tool for clinicians, which concentrates practical information needed for the management of oral complications of cancer patients. This CPS is focused on the management of oral manifestations of chronic graft-versus-host-disease (cGVHD). METHODS: This CPS was developed based on critical evaluation of the literature followed by a structured discussion of a group of leading experts, members of the Oral Care Study Group of MASCC/ISOO. The information is presented in the form of succinct bullets and table to generate a short manual about the best standard of care. RESULTS: The treatment goals in oral cGVHD are to relieve pain and xerostomia, improve oral function, prevent secondary infection, prevent deterioration of the dentition, and detect malignant transformation as early as possible. The prevention and treatment measures for oral mucosal lesions, hypofunction of the salivary glands, and sclerodermatous changes in the oral and perioral tissues are detailed, as well as the possible complications and side effects of these interventions. CONCLUSIONS: Patients post allogeneic hematopoietic cell transplantations, with cGVHD manifest in the oral and perioral tissues, should be regularly monitored and treated as needed by an oral care practitioner. This CPS provides the clinician with practical tools for examining, preventing, and treating the various sequalae that may affect the oral cavity in these patients.

Is micronucleus assay a useful marker in gingiva, tongue, and palate for evaluating cytogenetic damage induced by chemical, physical, and biological agents in vivo? A systematic review with meta-analysis.

The present systematic review (SR) aims to evaluate manuscripts in order to help further elucidate the following question: is the micronucleus assay (MA) also a useful marker in gingiva, tongue, and palate for evaluating cytogenetic damage in vivo? A search was performed through the electronic databases PubMed/Medline, Scopus, and Web of Science, all studies published up to December 2023. The comparisons were defined as standardized mean difference (SMD), and 95% confidence intervals (CIs) were established. Full manuscripts from 34 studies were carefully selected and reviewed in this setting. Our results demonstrate that the MA may be a useful biomarker of gingival tissue damage in vivo, and this tissue could be a useful alternative to the buccal mucosa. The meta-analysis analyzing the different sites regardless of the deleterious factor studied, the buccal mucosa (SMD = 0.69, 95% CI, - 0.49 to 1.88, p = 0.25) and gingiva (SMD = 0.31, 95% CI, - 0.11 to 0.72, p = 0.15), showed similar results and different outcome for the tongue (SMD = 1.19, 95% CI, 0.47 to 1.91, p = 0.001). In summary, our conclusion suggests that the MA can be a useful marker for detecting DNA damage in gingiva in vivo and that this tissue could be effective site for smearing.

Patients journey to diagnosis and treatment of oral mucosal lesions: A report on three cases.

Delays in diagnosis and management of patients with oral mucosal lesions have serious implications for the patients. Early referral and collaboration between HCPs and OM specialists are essential in improving patients' quality of life and outcomes.

The mucosal released-coronally advanced flap: A novel surgical approach-A case report.

BACKGROUND: The coronally advanced flap (CAF) can be a predictable surgical technique for the treatment of gingival recessions. However, the characteristics of the defect (e.g., limited amount of keratinized gingiva or flap tension, etc.) may limit the use of the CAF with a possible requirement of additional surgical interventions (i.e., the use of a tissue graft to be harvested from donor sites or connective tissue substitutes). METHODS: A 28-year-old woman patient, with no history of periodontal disease, came for referral presenting receding gums as a chief complaint, poor esthetics, and dentinal hypersensitivity at the buccal surface of teeth 11, 12, and 13. Clinically, she presented a thick phenotype with gingival recession type, RT1, with detectable cemento-enamel junction (A‒) in the second quadrant. To reduce the need of harvesting soft tissue grafts, the amount of cutting of muscles and vessels from the inner portion of the flap and mitigate the postoperative discomfort associated with the CAF, a novel surgical approach is described here using an advanced flap that incorporates an external incision along the mucogingival junction. RESULTS: The average root coverage achieved with the novel procedure presented in this case report was 95%, along with an increased amount of keratinized gingiva and minimal postoperative patient's discomfort. CONCLUSIONS: The mucosal released CAF is a promising technique in which the CAF technique alone may not be an indication. KEY POINTS: This technique has the following advantages: Reduce the need of harvesting soft tissue grafts. Reduce the amount of cutting of muscles and vessels from the inner portion of the flap. Minimal postoperative discomfort for the patient.

[Assessment of the condition of organs and tissues of the oral cavity in people with dentition defects against the background of metabolic syndrome]. / Otsenka sostoyaniya organov i tkanei rta u lits s defektami zubnykh ryadov na fone metabolicheskogo sindroma.

OBJECTIVE: The aim of the study is comparative analysis of the condition of oral organs and tissues in people with metabolic syndrome (MS) of varying severity before orthopedic dental rehabilitation based on dental implants. MATERIAL AND METHODS: 255 patients (151 women and 104 men) aged from 35 to 65 years were examined. 3 groups were formed: 2 study groups and a comparison group. Groups 1 and 2 included individuals with excess body weight and MS. The control group consisted of 88 people without MS. An index assessment of the condition of the periodontium and tissue structures of the alveolar bone (according to cone-beam computed tomography), microcirculation in the gingival mucosa was carried out using laser Doppler flowmetry. RESULTS: The analysis of the periodontal condition indicators showed that in all groups of patients with MS, periodontal pathology occurred, the value of which was significantly higher than in patients of the control group (p <0.05). The analysis of bone tissue according to CBCT data showed that the most favorable conditions (type 1 and type 2 of bone according to Misch) for dental implantation are found in people without MS, respectively 3.5% and 35.1% of cases. The intensity of blood flow (σ) was 21.2% lower in group 1 and 48% in group 2, compared with the control group. Vasomotor activity (Kv) was 13.2% lower in the first group and 35% lower in the second group. A decrease in amplitudes in the area of all rhythms in the LDF gram was found: low-frequency - by 15.6%, high-frequency - by 16.9%, pulse - by 3.6%. CONCLUSION: Changes occurring in the organs and tissues of the mouth against the background of MS of varying severity lead to a decrease in tissue perfusion with blood and blood flow activity, a local decrease in bone density, and as a result, pathological changes in periodontal tissues. Before performing dental rehabilitation, it is necessary to take into account all the risks of possible complications caused by the general condition of organs and systems of people with MS.

[Urethral reconstruction]. / Harnröhrenrekonstruktion.

A urethral stricture is an abnormal narrowing of the urethra due to spongiofibrosis of the urethral mucosa and the underlying corpus spongiosum. The diagnostics include uroflowmetry, sonography and radiology. For penile strictures the success rate of endoscopic treatment is low. Therefore, urethroplasty should always be performed, preferably using oral mucosa. Depending on the complexity, reconstruction must be carried out in one or multiple stages. For short bulbous strictures endoscopic treatment can primarily be carried out. In the case of recurrence urethroplasty should be carried out. The indications for urethral reconstruction are primarily given for long bulbous strictures. Depending on the length and extent of the stricture, a scar resection and end-to-end anastomosis, non-transsecting end-to-end anastomosis or augmentation urethroplasty can be performed. Perineal urethrostomy (the so-called boutonnière procedure) is a treatment option for patients with complex strictures or for patients who want a straightforward solution.

Association of Fordyce Granules with Skin Types - A Cross-Sectional Study.

Background: Fordyce granules, sometimes referred to as Fordyce dots, are aberrant sebaceous glands that present as diminutive, non-painful, elevated lesions exhibiting a yellowish or whitish hue, measuring 1 to 3 mm in diameter, and manifesting inside the oral cavity. Likewise, these particles may also be seen in the vaginal region and inside the oral cavity. Aim: The primary objective of the current study is to evaluate the potential association between Fordyce granules and the skin type of individuals who seek dental care at the Dental Clinics of Qassim University. Materials and Methods: The current cross-sectional research was undertaken at the Dental Clinics of Qassim University, with a sample of 87 patients diagnosed with Fordyce's granules. The research consisted of a heterogeneous sample of participants, including individuals of all genders, ranging in age from 18 to 85 years. The study included a comprehensive evaluation of several anatomical regions to identify the existence of Fordyce's granules. This examination was conducted by a single examiner who had undergone calibration. Additionally, the participants' skin types were established using the Baumann Skin Typing System questionnaire. The data that was gathered was afterward analyzed utilizing statistical methods via the use of SPSS software. A pre-set significance level was established at P < 0.05. Results: The distribution of skin types among the study participants with Fordyce's granules were found to be oily skin (51.3%), dry skin (47.9%), sensitive skin (49.3%), and resistant skin (56.3%). The results of the research showed that there was no statistically significant correlation between the two variables, i.e. skin type and the presence of Fordyce's granules. This conclusion is supported by the increased P values of 0.941 for those with oily skin and 0.785 for individuals with dry skin. Conclusion: No relation between skin type and Fordyce's granules in the current study.

Topical Adipose Mesenchymal Stem cell metabolites regulate the expression of MMP-1, MMP-9, EGF, TGF-ß in oral mucosa ulcer rat model.

Objective: Matrix metalloproteinase (MMP-1 and -9), Epidermal Growth Factor (EGF), and Transforming Growth factor (TGF)-ß are expressed in the oral ulcer wound-healing process. The Adipose mesenchymal stem cell metabolites (AdMSCMs) may accelerate wound-healing. This study aimed to investigate the expression of MMP-1, MMP-9, EGF, and TGF-ß in the oral mucosa ulcer rat model treated with topical AdMSCMs. Materials and Methods: Oral ulcer models were created in twenty healthy male Wistar rats (Rattus novergicus) divided into AdMSCMs and control groups. The oral ulcer model was treated topically using AdMSCMs oral gel three times daily for 3 and 7 days. The expression of MMP-1, MMP-9, EGF, TGF-ß was evaluated through histological examination using the immunohistochemistry method. Independent t-test was used to compare the mean of expression of MMP-1, MMP-9, EGF, TGF-ß between control and treatment groups (AdMSCMs), and paired t-test was used to analyze the mean between day 3 and day 7 of each group. Results: A lower expression of MMP-1, MMP-9 in AdMSCMs group and higher expression EGF and TGF-ß in AdMSCMs group compared to the control group in day 3 and day 7. Independent t-test results showed a significant difference in the expression of MMP-1, MMP-9, EGF between the control and AdMSCMs group in day 3 and day 7. Only TGF-ß expression mean difference between day 3 and day 7 showed a significant difference compared to the control groups (p < 0.05). Conclusions: AdMSCMs oral gel may accelerate oral ulcer healing models by reducing the expression MMP-1, MMP-9, and increasing EGF and TGF-ß expressions during the wound-healing process.

Efficacy of topical agents in oral mucositis prevention: Systematic review and network meta-analysis.

BACKGROUND: Oral mucositis (OM) is considered one of the most common side effects of patients undergoing cancer therapy. OM prevention plays a crucial role in the effectiveness of cancer treatment and the patient's quality of life. Different preventive treatments have been proposed in clinical trials, however with inconclusive results. MATERIALS AND METHODS: A systematic review search was conducted in PubMed, Scopus, Web of Science, and Cochrane Database to answer the PICO question: in cancer patients, do specific topical agents compared to standard treatments or placebo reduce the onset and severity of oral mucositis? The risk of bias was assessed, and a network meta-analysis was conducted. RESULTS: Of 2913 results, 30 randomized clinical trials were considered suitable for inclusion. A total of 2564 patients were analyzed, of which 1284 belonged to the test group and 1280 belonged to the control group. Natural products were the most used, followed mainly by antimicrobial agents, coating agents, and basic oral care measures. Topical sucralfate resulted in the most powerful intervention for the OM prevention (OR = 0.04, 95%C.I. = 0.01-0.25, p-value = 0.001). CONCLUSION: Due to its cytoprotective action, low cost, ease of administration, and safety, sucralfate could become a potential ally to prevent the onset of OM during cancer therapy.

MHC-II presentation by oral Langerhans cells impacts intraepithelial Tc17 abundance and Candida albicans oral infection via CD4 T cells.

In a murine model (LCΔMHC-II) designed to abolish MHC-II expression in Langerhans cells (LCs), ∼18% of oral LCs retain MHC-II, yet oral mucosal CD4 T cells numbers are unaffected. In LCΔMHC-II mice, we now show that oral intraepithelial conventional CD8αß T cell numbers expand 30-fold. Antibody-mediated ablation of CD4 T cells in wild-type mice also resulted in CD8αß T cell expansion in the oral mucosa. Therefore, we hypothesize that MHC class II molecules uniquely expressed on Langerhans cells mediate the suppression of intraepithelial resident-memory CD8 T cell numbers via a CD4 T cell-dependent mechanism. The expanded oral CD8 T cells co-expressed CD69 and CD103 and the majority produced IL-17A [CD8 T cytotoxic (Tc)17 cells] with a minority expressing IFN-γ (Tc1 cells). These oral CD8 T cells showed broad T cell receptor Vß gene usage indicating responsiveness to diverse oral antigens. Generally supporting Tc17 cells, transforming growth factor-ß1 (TGF-ß1) increased 4-fold in the oral mucosa. Surprisingly, blocking TGF-ß1 signaling with the TGF-R1 kinase inhibitor, LY364947, did not reduce Tc17 or Tc1 numbers. Nonetheless, LY364947 increased γδ T cell numbers and decreased CD49a expression on Tc1 cells. Although IL-17A-expressing γδ T cells were reduced by 30%, LCΔMHC-II mice displayed greater resistance to Candida albicans in early stages of oral infection. These findings suggest that modulating MHC-II expression in oral LC may be an effective strategy against fungal infections at mucosal surfaces counteracted by IL-17A-dependent mechanisms.

Collagen: The Superior Material for Full-Thickness Oral Mucosa Tissue Engineering.

BACKGROUND: Tissue engineering has significantly progressed in developing full-thickness oral mucosa constructs designed to replicate the natural oral mucosa. These constructs serve as valuable in vitro models for biocompatibility testing and oral disease modeling and hold clinical potential for replacing damaged or lost oral soft tissue. However, one of the major challenges in tissue engineering of the oral mucosa is the identification of an appropriate scaffold with optimal porosity, interconnected porous networks, biodegradability, and biocompatibility. These characteristics facilitate cell migration, nutrient delivery, and vascularization. Various biomaterials have been investigated for constructing tissue-engineered oral mucosa models; collagen has demonstrated superior outcomes compared with other materials. HIGHLIGHT: This review discusses the different types of tissue-engineered oral mucosa developed using various materials and includes articles published between January 2000 and December 2022 in PubMed and Google Scholar. The review focuses on the superiority of collagen-based scaffolds for tissue engineering of oral mucosa, explores in vitro applications, and discusses potential clinical applications. CONCLUSION: Among the various scaffold materials used for engineering the connective tissue of the oral mucosa, collagen-based scaffolds possess excellent biological properties, offering high-quality oral mucosa constructs and high resemblance to the native human oral mucosa in terms of histology and expression of various differentiation markers.

[Precancers of the oral mucosa: clinic, diagnostics]. / Predraki slizistoi obolochki rta: klinika i diagnostika.

OBJECTIVE: The aim of the study. Improving the efficiency of diagnosis and detailing the features of the clinic of «potentially malignant¼ diseases of the oral mucosa. MATERIALS AND METHODS: Clinical and laboratory examination of 124 patients of the department of oral mucosa diseases aged 35 to 80 years, among whom there were 75 women and 49 men, with diseases such as erythroplakia - 12 patients, verrucous leukoplakia - 52 patients, erosive form of leukoplakia - 35 patients, cheilitis Manganotti - 25 patients. Histological and immunohistochemical methods of investigation were used as diagnostics. To assess the proliferative activity of epithelial cells, the determination of the Ki-67 index was used. The synthesis of keratin 15 (K15) in epithelial layers was determined as a diagnostic criterion for the severity of neoplasia. The expression of human papillomavirus type 16 (HPV 16) antigens and p16INK4a protein in epithelial cells was studied, as well as the expression of p53 protein. RESULTS: A high prevalence of p53 mutations was observed in patients with erythroplakia. In leukoplakia, the expression of the Ki-67 protein was detected in the cell nuclei in both the basal and parabasal layers of the multilayer squamous epithelium, in 77% of cases, the expression of the p16INK4a protein in the epithelial nuclei with varying degrees of dysplastic changes was noted, and a positive reaction to HPV16 was also observed in the cell nuclei and cytoplasm of epithelial cells in the basal, parabasal and spiny epithelial layers. The appearance of K15 in the cytoplasm of cells above the basal layer with abrasive precancerous cheilitis was found in 48% of cases. CONCLUSION: To diagnose early manifestations of neoplastic processes in «potentially malignant¼ diseases of the oral mucosa, it is necessary to use both classical histological and immunohistochemical methods of investigation with various markers.

Biological Evaluation of Oral Care Products Using 3D Tissue-Engineered In Vitro Models of Plaque-Induced Gingivitis.

BACKGROUND: The aim of this study was to investigate and visualize the anti-inflammatory and anti-bacterial effects of different oral care products using an infected and inflamed 3D tissue-engineered gingival mucosal model. METHODS: A 3D full-thickness oral mucosal model was engineered inside tissue culture inserts using collagen hydrogels populated with human gingival fibroblasts and THP-1 monocytes and layered with oral epithelial cell lines. Oral saliva bacteria were cultured and added to the surface of the models and inflammation was further simulated with lipopolysaccharide (LPS) of Escherichia coli. The 3D models were exposed to three different types of toothpastes, a chlorhexidine antiseptic mouthwash, different antibiotics, and a mechanical rinse with phosphate-buffered saline (PBS) prior to biological evaluation using the PrestoBlue tissue viability assay, histology, optical coherence tomography (OCT), confocal microscopy, and measurement of the release of the inflammatory markers IL-1ß, IL-6, and IL-8 with ELISA. RESULTS: Multiple-endpoint analyses of the infected oral mucosal models treated with different anti-bacterial agents showed consistent outcomes in terms of tissue viability, histology, OCT, and confocal microscopy findings. In terms of anti-inflammatory testings, the positive control group showed the highest level of inflammation compared with all other groups. Depending on the anti-bacterial and anti-inflammatory potential of the test groups, different levels of inflammation were observed in the test groups. CONCLUSIONS: The inflamed 3D oral mucosal model developed in this study has the potential to be used as a suitable in vitro model for testing the biocompatibility, anti-inflammatory, and anti-bacterial properties of oral care products including mouthwashes and toothpastes. The results of this study indicate that the chlorhexidine mouthwash has both anti-bacterial and cytotoxic effects on the 3D oral mucosal model. Hyaluronic-acid-containing toothpaste has significant anti-bacterial and anti-inflammatory effects on the 3D oral mucosal model.

A Tissue Engineered 3D Model of Cancer Cell Invasion for Human Head and Neck Squamous-Cell Carcinoma.

Head and neck squamous-cell carcinoma (HNSCC) is associated with aggressive local invasiveness, being a main reason for its poor prognosis. The exact mechanisms underlying the strong invasive abilities of HNSCC remain to be elucidated. Therefore, there is a need for in vitro models to study the interplay between cancer cells and normal adjacent tissue at the invasive tumor front. To generate oral mucosa tissue models (OMM), primary keratinocytes and fibroblasts from human oral mucosa were isolated and seeded onto a biological scaffold derived from porcine small intestinal submucosa with preserved mucosa. Thereafter, we tested different methods (single tumor cells, tumor cell spots, spheroids) to integrate the human cancer cell line FaDu to generate an invasive three-dimensional model of HNSCC. All models were subjected to morphological analysis by histology and immunohistochemistry. We successfully built OMM tissue models with high in vivo-in vitro correlation. The integration of FaDu cell spots and spheroids into the OMM failed. However, with the integration of single FaDu cells into the OMM, invasive tumor cell clusters developed. Between segments of regular epithelial differentiation of the OMM, these clusters showed a basal membrane penetration and lamina propria infiltration. Primary human fibroblasts and keratinocytes seeded onto a porcine carrier structure are suitable to build an OMM. The HNSCC model with integrated FaDu cells could enable subsequent investigations into cancer cell invasiveness.