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In this case series, we present four unique cases of Riga-Fede disease (RFD), a rare disorder characterized by mucosal trauma as a result of repetitive tongue protrusion against the incisors, leading to the development of a large oral mass/ulceration. Due to the rapid development and growth of these lesions mimicking malignancy, it is important for the general and pediatric otolaryngologist to correctly diagnose and treat this benign disorder. This series highlights the variable clinical presentations, along with comorbidities of RFD, as well as the importance of interdisciplinary care between the pediatric otolaryngologist and pediatric dentist in its management. Laryngoscope, 134:4803-4805, 2024., (© 2024 The Author(s). The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Oral ulcerative mucositis (OUM) is common in patients with cancer, particularly in those undergoing chemoradiation therapy. The effective management of OUM is crucial for continuous cancer care and patient well-being. Recent studies have advanced our understanding of the causes, leading to clinical trials toward novel treatments. This review focuses on the contemporary therapeutic landscape, and provides the latest insights into the mechanisms of mucosal healing and pain., Highlights: Management strategies for OUM in patients with cancer include maintaining good oral hygiene, reducing mucosal irritation against radiation, and using various topical analgesic treatments, including herbal medicines. However, the current management practices have limitations that necessitate the development of more efficacious and novel treatments. Molecular research on transient receptor potential (TRP) channels in the oral mucosa is crucial for understanding the mechanisms of wound healing and pain in patients with OUM. Targeting TRPV3 and TRPV4 can enhance wound healing through re-epithelialization. The suppression of TRPV1, TRPA1, and TRPV4 may be effective in alleviating OUM-induced pain., Conclusion: Research advancements have improved our understanding and potentially led to novel treatments that offer symptomatic relief. This progress highlights the importance of collaborations between clinical researchers and scientists in the development of innovative therapies., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: To conduct a systematic review and meta-analysis to assess the effectiveness of ozone therapy in oral ulcers healing when compared to placebo or active treatments., Materials and Methods: The search was carried out using PubMed, EMBASE, Scopus, and Lilacs databases. Clinical trials involving human participants were included. The Risk Ratio (RR) and the standardized mean difference (SMD) with 95%CI (confidence interval) were calculated. The ROBINS-I (risk of bias in non-randomized studies of interventions) and RoB2 (risk of bias tool for randomized trials) assessment tool was used to detect bias., Results: After the selection process, 12 studies were included. The meta-analysis showed that ozone therapy helps to reduce the size of the traumatic and autoimmune ulcers (RR=-0.44; 95% CI -0.71,-0.17; I 2 =0%) in comparison to placebo. Regarding pain reduction, ozone was superior to placebo (RR = 1.29, 95% CI -1.6 to -0.95); I 2 =0%), and equivalent to topical corticosteroid and laser photobiomodulation (RR = 0.26, 95% CI -0.27,0.78, p = 0.34)., Conclusion: Ozone therapy is an alternative for accelerating healing and reducing pain for both traumatic and autoimmune ulcers. However, the quality of evidence is limited., Clinical Relevance: Oral ulcerations are usually painful and impact quality of life requiring different approaches to boost wound healing and reduce symptoms. For this purpose, ozone therapy is a promising strategy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Oral ulcers, superficial lesions on the surface of the oral mucosa, have a high incidence rate, and their main symptoms include local pain and erosion. Lipopolysaccharide (LPS)-preconditioned bone marrow mesenchymal stem cells and their secreted exosomes (LPS-pre-Exos) have been shown to promote recovery in various inflammatory conditions and wounds. However, studies documenting LPS-pre-Exos as a therapeutic intervention for oral mucosal-like diseases are lacking. In this study, we prepared a silk fibroin microneedle (MN) patch consisting of LPS-pre-Exos and zeolitic imidazolate framework-8 (ZIF-8) that localized at the tip and base, respectively, and used this MN patch for oral ulcer treatment. Upon insertion into the oral mucosa, continuous LPS-pre-Exos release was observed, which promoted macrophage polarization and tissue healing. Additionally, the ZIF-8 framework in the MN patch facilitated the controlled release of Zn 2+ , which demonstrated potent antimicrobial properties via synergistic effects. The in vitro experimental results showed that the silk fibroin MN patch can continuously release LPS-pre-Exos and Zn 2+ for more than 7 days. Thus, the LPS-pre-Exos and ZIF-8-loaded silk fibroin MN patch exhibited good anti-inflammatory and antibacterial properties, promoting oral ulcer healing, and showed good histocompatibility. Hence, it may represent a potentially valuable strategy for facilitating oral ulcer healing.

Background: Oral ulcers are a common side effect of chemotherapy and affect patients' quality of life. While stem cell transplantation is a potential treatment for oral ulcers, its efficacy is limited as the stem cells tend to remain in the affected area for a short time. This study aims to develop a treatment for oral ulcers by using trimethyl chitosan (TMC) hydrogel with human tonsil-derived stem cells (hTMSCs) to increase the therapeutic effect of stem cells and investigate their effectiveness., Methods: Animals were divided into four experimental groups: Control, TMC hydrogel, hTMSCs, and hTMSCs loaded in TMC hydrogel (Hydrogel + hTMSCs) (each n = 8). Oral ulcers were chemically induced by anesthetizing the rats followed by injection of dilute acetic acid in the right buccal mucosa. After confirming the presence of oral ulcers in the animals, a single subcutaneous injection of 100 µL of each treatment was applied to the ulcer area. Histological analyses were performed to measure inflammatory cells, oral mucosal thickness, and fibrosis levels. The expression level of inflammatory cytokines was also measured using RT-PCR to gauge therapeutic the effect., Results: The ulcer size was significantly reduced in the TMC hydrogel + hTMSCs group compared to the control group. The stem cells in the tissue were only observed until Day 3 in the hTMSCs treated group, while the injected stem cells in the TMC Hydrogel + hTMSCs group were still present until day 7. Cytokine analysis related to the inflammatory response in the tissue confirmed that the TMC Hydrogel + hTMSCs treated group demonstrated superior wound healing compared to other experimental groups., Conclusion: This study has shown that the adhesion and viability of current stem cell therapies can be resolved by utilizing a hydrogel prepared with TMC and combining it with hTMSCs. The combined treatment can promote rapid healing of oral cavity wounds by enhancing anti-inflammatory effects and expediting wound healing. Therefore, hTMSC loaded in TMC hydrogel was the most effective wound-healing approach among all four treatment groups prolonging stem cell survival. However, further research is necessary to minimize the initial inflammatory response of biomaterials and assess the safety and long-term effects for potential clinical applications., (© 2024. The Author(s).)

Background: Riga-Fede disease (RFD) presents as oral mucosal ulceration in anatomical juxtaposition to sharp dental surfaces., Case Presentation: A 7-month-old healthy male presented to the pediatric dentist for an emergency appointment. His mother was concerned about episodic, recurrent, and excessive bleeding from his mouth for three weeks. She reported that her son would often wake up in "a pool of blood". The pediatrician assessed the patient when oral bleeding first started and prescribed magic mouthwash. This did not resolve the problem. The mother then took the child to an urgent care clinic, where she was referred to a pediatric dentist. The pediatric dentist noted a sublingual traumatic, granulomatous ulcer on the ventral surface of the tongue, extending up to the tip of the tongue. The mandibular primary central incisors had recently erupted. The pediatric dentist established a clinical diagnosis of RFD. Incisal edges were smoothened with dental polishing tips on a slow-speed handpiece and topical fluoride varnish was applied to the teeth. The size of the ulceration decreased over two weeks. However, in three weeks, there was another bleeding episode. The pediatric dentist smoothened the incisal edges again, followed by a fluoride varnish application. Eight weeks after the initial dental intervention, the lesion resolved completely without further bleeding., Discussion: The details of this case report highlight the maternal concerns, interprofessional educational touchpoints, scope for interprofessional collaborative care, and noninvasive management of Riga-Fede disease., Conclusion: In neurotypical patients, conservative dental management by smoothening sharp dental surfaces can resolve RFD. RFD should be differentiated from viral illnesses which present with oral ulcerations., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Neutropenic ulcerations are characterized by mucosal ulcerations which occur in the presence of neutropenia, suggesting a direct link between neutropenia and mucosal ulceration. An oral ulcer can be labeled as "neutropenic" only if the patients have primary (typically congenital) or secondary neutropenia, and neutropenia is the sole causative factor. Oral mucosal ulcers observed in patients undergoing oncologic therapy may also be termed as "neutropenic ulcers", but the pathogenesis of these oral ulcers more likely involves mucosal events related to trauma, microbial factors, and direct cytotoxicity. In cancer patients, the early appearance of oral ulcers is often attributed to oral mucositis which is a condition primarily caused by the direct mucosal cytotoxicity of chemotherapeutic agents and radiation therapy. Oral ulcers that develop later during or after active cancer therapy may result from intraoral trauma and typically manifest on non-keratinized areas of the oral mucosa which are more susceptible to mucosal damage. In patients undergoing chemotherapy, factors such as disturbances in mucosal barrier function as well as bone marrow suppression lead to reduced neutrophil count and function, and can contribute to the development of oral ulcers. While the etiology of oral ulcers in cancer therapy receiving patients can vary, it is important to emphasize that the host's response plays a crucial role in the progression and repair process of these lesions. This narrative review presents the etiopathogenesis, clinical presentation, and potential management approaches for oral ulcerations in neutropenic patients, with a particular focus on clarifying the usage of the term "neutropenic ulcer" since this term lacks diagnostic specificity and can be misleading in clinical practice regarding the underlying causes and treatment strategies., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Eosinophilic ulcer of the oral mucosa is a benign, reactive, self-limited lesion. Its pathogenesis is unclear, and it clinically manifests as a punched-out ulcer with surrounding indurated border, raising suspicion for a possible malignancy. On histology, an acute and chronic dense inflammatory infiltrate can be appreciated, which can extend to the deep underlying tissue (including skeletal muscle). Eosinophils are especially conspicuous on hematoxylin and eosin staining and might play an important role in the development of the ulcer. Removal of possible triggers followed by monitoring and possible biopsy are among the initial recommendations. Most lesions heal spontaneously without the need for intervention. This review aims at assisting dermatologists to easily recognize this entity, avoiding unnecessary interventions and apprehension., (© 2021 the International Society of Dermatology.)

Objective: To review common presentation of oral ulcers in children and discuss management of symptoms and subsequent investigation., Conclusion: Although a common presentation in children, diagnosis can be challenging. Thorough history taking is critical towards diagnosis and supports signposting to relevant specialities. Clinicians should be able to support first-line symptomatic management of oral ulceration., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

The complexity of oral ulcerations poses considerable diagnostic and therapeutic challenges to oral specialists. The expert consensus was conducted to summarize the diagnostic work-up for difficult and complicated oral ulcers, based on factors such as detailed clinical medical history inquiry, histopathological examination, and ulceration-related systemic diseases screening. Not only it can provide a standardized procedure of oral ulceration, but also it can improve the diagnostic efficiency, in order to avoid misdiagnosis and missed diagnosis., (© 2022. The Author(s).)

Ulceration of the oral cavity is common and a frequent reason for referral to secondary and tertiary centres. Epstein-Barr virus (EBV)-related mucocutaneous ulceration, however, is a rare cause of oral ulceration that has been described only recently. Histologically these lesions resemble lymphomas; however, their management and prognosis differ significantly. We present a case of EBV-induced oral ulceration and discuss the diagnosis and management of and available literature for the condition, which was treated successfully through conservative measures alone.

Caustic ingestion is a potentially detrimental event that can cause serious devastating damage on contact with tissues. Local exposure is associated with severe pain, swelling and ulceration. Caustics-induced oral ulcers can be painful enough to compromise the patient's quality of life. Treatment of oral ulcers is crucial in clinical practice. Albeit, some ulcers do not respond adequately to the conventional treatment. The current study was conducted to evaluate the potential healing effects of topical Salvadora persica (SP) extract, low-level laser (LLL) and high-level laser (HLL) therapies in a rabbit model of caustic-induced tongue ulcers and explore the underlying mechanisms. Fifty male rabbits with a caustic induced tongue ulcers were included in the study. Rabbits were equally divided into four groups: positive control (ulcer) group, SP, LLL and HLL groups in addition to the negative control (healthy) group. All treatments were given thrice weekly for 14 days. Results showed that acetic acid-induced tongue ulcers caused extensive structural tongue damage secondary to overexpression of apoptotic BAX, pathological angiogenesis indicated by VEGF overexpression, marked collagen fibers deposition as well as upregulation of tissue pro-inflammatory TNF-α and upregulation of tissue anti-inflammatory IL-10. The healing potential of topical SP, LLL and HLL therapy are mostly comparable. In conclusion, acetic acid-induced extensive tongue damage. Topical SP extract, LLL and HLL are equally effective therapies against caustics-induced tongue ulcers. However, we recommend SP extract, owing to its safety, non-invasiveness, availability and low cost.

Background: Oral ulcers (OU) is a common oral mucosal disease manifested with obvious pain; in some studies, the efficacy of acupuncture in OU has been confirmed, but the systematic reviews and meta-analyses for them are lacking. Our aim is to evaluate the efficacy and safety of acupuncture in the treatment of OU., Methods: Relevant randomized controlled trials (RCTs), quasi RCTs and non-RCTs will be identified by systematic searching from the following electronic databases: PubMed, Embase, the Cochrane Library, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, China Science and Technology Journal database, and Wanfang Data (since inception of the databases to present). In addition, ongoing trials will be retrieved from the Chinese Clinical Trial Register, World Health Organization International Clinical Trials Registry Platform, Clinical Trials, and The Clinical Trials Register. Grey literature will be also taken into consideration, including academic dissertation, minutes of the meeting from Chinese Biomedical Literature Database, China National Knowledge Infrastructure, China Science and Technology Journal database, and Wanfang Data. There are no language restrictions., Results: Ethical approval is not required because this study is based on published papers. After peer-review, the study will be disseminated in scientific journals and conferences., Conclusion: This systematic review will provide evidence for the efficacy and safety of acupuncture for Oral ulcers., Trial Registration Number: CRD42020144911.

Electrospinning provides a simple and convenient method to fabricate nanofibrous meshes. However, the nanofiber productivity is often limited to the laboratory scale, which cannot satisfy the requirements of practical application. In this study, we developed a novel needleless electrospinning spinneret based on a double-ring slit to fabricate drug-loaded nanofibrous meshes. In contrast to the conventional single-needle electrospinning spinneret, our needless spinneret can significantly improve nanofiber productivity due to the simultaneous formation of multiple jets during electrospinning. Curcumin-loaded poly(l-lactic acid) (PLLA) nanofiber meshes with various concentrations and on the large scale were manufactured by employing our developed needleless spinneret-based electrospinning device. We systematically investigated the drug release behaviors, antioxidant properties, anti-inflammatory attributes, and cytotoxicity of the curcumin-loaded PLLA nanofibrous meshes. Furthermore, a bilayer nanofibrous composite mesh was successfully generated by electrospinning curcumin-loaded PLLA solution and diclofenac sodium loaded poly(ethylene oxide) solution in a predetermined time sequence, which revealed potent antibacterial properties. Subsequently, novel mucoadhesive patches were assembled by combining the bilayer composite nanofibrous meshes with (hydroxypropyl)methyl cellulose based mucoadhesive film. The multilayered mucoadhesive patch has excellent adhesion properties on the porcine buccal mucosa. Overall, our double-ring slit spinneret can provide a novel method to rapidly produce large-scale drug-loaded nanofibrous meshes to fabricate mucoadhesive patches. The multiple-layered mucoadhesive patches enable the incorporation of multiple drugs with different targets of action, such as analgesic, anti-inflammatory, and antimicrobial compounds, for mouth ulcer or other oral disease treatments.

Background: There is no mainstay protocol for management of Methotrexate-induced oral ulcers; commonly used protocols are cessation of Methotrexate, folic acid treatment, corticosteroids or combination. A new era of oral ulcers management is represented by platelet concentrates. The current study assessed the effect of topical human platelet lysate compared to topical Clobetasol Propionate in management of methotrexate-induced oral ulceration in rheumatoid arthritis patients., Methods: This randomized controlled clinical trial include 30 patients in two parallel groups (intervention - human platelet lysate, control - Clobetasol Propionate), with allocation ratio 1:1. Outcome measures were pain intensity using numerical rating scale, WHO scale for oral mucositis, measuring size of the largest ulcer and total number of oral ulcers., Results: A statistically significant difference was detected between HPL and Clobetasol groups on comparing numerical rating scale, WHO mucositis scale, size and total number of oral ulcers throughout all visits. A considerable quick pain reduction and clinical improvement were noticed in HPL group compared to Clobetasol., Conclusion: Human platelet lysate has superior effect when compared to one of the most potent topical corticosteroids, Clobetasol Propionate, in reducing pain and clinical signs of Methotrexate-induced oral ulcers in patients with rheumatoid arthritis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The current use of steroids or pharmacological immunomodulators for the treatment of intractable oral ulceration is ineffective, necessitating newer cell-based therapeutic approaches. We examined the potential efficacy of an oral mucosa equivalent developed in this study in an in vivo model of repeat major oral ulceration mimicking the intractable oral ulceration observed clinically. Oral mucosal samples and plasma fibrin were obtained from Sprague-Dawley rats. The oral mucosa equivalents were prepared with cultured mucosal keratinocytes and plasma fibrin mixed with cultured fibroblasts. Ulcers were chemically induced on the rat buccal mucosa thrice in 3 weeks and covered with or without mucosa equivalents. Gross and microscopic findings and mRNA expression levels were compared between the ulcer control and mucosa equivalent groups. Oral mucosal keratinocytes and fibroblasts were cultured in vitro to achieve high viability and colony-forming efficiency. The equivalents showed epithelial and subepithelial structures similar to those of oral mucosa and exhibited high p63 positivity. In the in vivo study, ulceration was resolved earlier without significant granulation or scarring in the equivalent group than in control group (p < 0.05). Microscopic examinations revealed rapid re-epithelialization and less fibrosis in the equivalent group than in the control group (p < 0.05). Mucosa equivalent-covered ulcers showed histological characteristics similar to those of the normal buccal mucosa and exhibited lower expression of TGFB1, ACTA2, and FN1 mRNAs than the control group. The in vitro-engineered oral mucosa equivalent promotes ulcer healing without scarring and functional deficits. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1779-1785, 2019., (© 2018 Wiley Periodicals, Inc.)

A 39-year-old woman sought specialized treatment complaining of a large, painful oral ulcer in the right buccal vestibule after receiving emergency endodontic treatment 3 days earlier. The patient reported that the tooth, the mandibular right first premolar, was not isolated with a rubber dam and that she felt the extrusion of a liquid in the buccal tissues. Clinically, a necrotic area with raised erythematous borders was observed in the mandibular right side. The clinical diagnosis was a chemically induced ulcer caused by a sodium hypochlorite accident. Dexamethasone and amoxicillin were prescribed to control pain and prevent secondary infection. The large size of the lesion was an indication for application of low-level laser therapy (LLLT), which was delivered at a wavelength of 685 nm (output power, 30 mW; power density, 0.5 mW⁄cm2 ; energy density, 6 J⁄cm2 ) every 2 days for a total of 6 sessions. The LLLT was applied to the necrotic area with a punctual mode (2 points) for 12 seconds per point. The patient reported a substantial reduction in pain after the second application, and the wound was completely healed after 6 sessions. The results observed in this patient suggest that LLLT could aid patients in recovering from NaOCl-related lesions., Competing Interests: The authors report no conflicts of interest pertaining to any of the products or companies discussed in this article.

We sought to examine the management and referral of nonhealing mouth ulcer presentations in Australian community pharmacies in the Greater Brisbane region. Trained simulated patients visited 220 randomly selected community pharmacies within the Greater Brisbane region in 2016. Simulated patients enacted two nonhealing (>1 month) mouth ulcer scenarios: A direct product request (DPR) (n = 110) and a symptom-based request (SBR) (n = 110). Results were documented and evaluated against Australian national pharmacy practice standards. Referral rates for pharmacy staff (pharmacist, pharmacy assistant or mixed-pharmacist and assistant) were also assessed. Australian pharmacy practice standards recommend staff ask six key questions during SBR and DPR consultations to enable informed decision-making. Two questions relating to identifying the patient and their symptoms were asked in the majority of interactions (76% and 69% respectively); the remaining four questions relating to symptom duration, treatments tried, other medications, and medical conditions were enquired in only 32%, 53%, 31%, and 27% of interactions, respectively. Simulated patients were referred to the doctor/dentist in only 11.8% of all interactions (both scenarios requiring referral). Overall, staff handling of nonhealing mouth ulcer consultations was suboptimal compared to national professional standards. In particular, duration of the nonhealing mouth ulcer was enquired in less than one-third of consultations potentially resulting in low referral rates by staff. This study identifies the need for increased oral cancer awareness and education for community pharmacy staff and reinforcing the importance of practising according to professional standards to effectively screen for potentially cancerous nonhealing mouth lesions., (© 2018 John Wiley & Sons Ltd.)

Competing Interests: Competing interests: None declared.

Background: Oral chronic graft-versus-host disease (cGvHD) impairs oral function and patients' quality of life. Some lesions are refractory to local and systemic immunosuppressive therapy, and new therapeutic modalities are required. The aim of the study was to assess the efficacy and safety of topical application of autologous platelet gel (PG) in patients with oral cGvHD., Study Design and Methods: PG was prepared from autologous blood and applied on ulcerous lesions using an automated system. The oral cGvHD was assessed using the 273-point Oral Mucositis Rating Scale (OMRS) prior and after completion of the PG treatment. The overall response to treatment of particular topography expressed as the total score on OMRS was compared to total score on National Institutes of Health cGvHD Oral Mucosal Score (NIH OMS). The pain intensity was measured by the Numeric Pain Rating Scale (NRS)., Results: In five patients, 12 autologous blood collections were performed; median 3 (range 1-3) per patient, and 26 PG applications were performed; median 6 (range 2-8) per patient. PG applications reduced lesions in oral cGvHD: median OMRS total score was reduced for 43.2% (range 9.6%-47.3%), and median NIH OMS total score for 27.3% (range 20.0%-50.0%) from baseline values. Median of pain intensity reduction on NRS scale was 57.1% (range 50%-100%). No side effects were observed., Conclusion: Application of autologous PG in oral cGvHD showed as an efficient and safe treatment option for patients who do not respond to standard local treatment., (© 2018 AABB.)

Radiation-induced oral mucositis affects patient quality of life and reduces tolerance to cancer therapy. Unfortunately, traditional treatments are insufficient for the treatment of mucositis and might elicit severe side effects. Due to their immunomodulatory and anti-inflammatory properties, the transplantation of mesenchymal stem cells (MSCs) is a potential therapeutic strategy for mucositis. However, systemically infused MSCs rarely reach inflamed sites, impacting their clinical efficacy. Previous studies have demonstrated that chemokine axes play an important role in MSC targeting. By systematically evaluating the expression patterns of chemokines in radiation/chemical-induced oral mucositis, we found that CXCL2 was highly expressed, whereas cultured MSCs negligibly express the CXCL2 receptor CXCR2. Thus, we explored the potential therapeutic benefits of the transplantation of CXCR 2 -overexpressing MSCs (MSCs CXCR2 ) for mucositis treatment. Indeed, MSCs CXCR2 exhibited enhanced targeting ability to the inflamed mucosa in radiation/chemical-induced oral mucositis mouse models. Furthermore, we found that MSC CXCR2 transplantation accelerated ulcer healing by suppressing the production of pro-inflammatory chemokines and radiogenic reactive oxygen species (ROS). Altogether, these findings indicate that CXCR2 overexpression in MSCs accelerates ulcer healing, providing new insights into cell-based therapy for radiation/chemical-induced oral mucositis.

Adipose tissue-derived stem cells (ASCs) are known to be tissue-healing promoters due to their cellular plasticity and secretion of paracrine factors. Cultured ASC sheets provide a novel method of ASC application and can retain ASCs at the targeted tissue. The purpose of this systematic review is to evaluate preclinical studies using ASC sheet transplantation therapy for promoting tissue healing. First, we searched databases to identify studies of ASC sheet therapy in different experimental animal models, and then determined the quality score of studies using SYRCLE's risk bias tool. A total of 18 included studies examined the role of ASC sheets on tissue healing and function in models for myocardial infarction, dilated cardiomyopathy, full-thickness skin wounds, hind limb ischemia, esophageal strictures, and oral ulcers. ASC sheet application after myocardial infarction improved survival rate, cardiac function, and capillary density and reduced the extent of fibrosis. Application of ASC sheets to a full-thickness skin wound decreased the wound size and stimulated wound maturation. In the hind limb ischemia model, ASC sheet application improved limb perfusion and capillary density, and decreased the amount of ischemic tissue and inflammation. ASC sheet application to mucosal wounds of the digestive tract accelerated wound healing and decreased the degree of stricture and fibrosis. Taken together, transplanted ASC sheets had a positive effect on tissue healing and reconstruction in these preclinical studies. The reported favorable effects of ASC sheet therapy in various tissue healing applications may be implemented in future translational studies. It is suggested that future preclinical animal model studies of ASC sheet therapy should concern standardization of culture techniques and investigate the mechanisms of action. In addition, clearly indicated experimental setups according to the SYRCLE's guidelines should improve study quality and validity.

Ulcerations and erosions of the oral mucosa are common and occur at any age. Their knowledge and recognition are essential to ensure optimal care at the earliest stage. Etiologies are numerous and the subject of different classifications. In this work, the authors address the most frequently encountered lesions, describing their main clinical presentations. A review of treatments is then proposed.

Oral ulcers are the most common mucosal sign in juvenile-onset systemic lupus erythematosus (JSLE). The ulcers are one of the key clinical features; however, the terminology of oral ulcers, especially in JSLE patients, is often vague and ill-defined. In fact, there are several clinical manifestations of oral ulcers in JSLE, and some lesions occur when the disease is active, indicating that early management of the disease should be started. Oral ulcers are classified as lupus erythematosus (LE) specific, where the lesional biopsy shows a unique pattern of mucosal change in LE, and LE nonspecific, where the ulcers and their histopathological findings can be found in other oral diseases. Here, the clinical manifestations, diagnosis and management of oral ulcers in JSLE patients are reviewed.

Pyoderma gangrenosum (PG) is a distinctive ulcerative skin disorder of unknown etiology, associated with an underlying systemic disease in up to 70% of cases. The condition is characterized by the appearance of one or more necrotic ulcers with a ragged undermined violaceous border and surrounding erythema. Lesions are often initiated by minor trauma. The condition can affect any anatomical site, however the head and neck are rarely involved. Although the oral cavity is subject to recurrent minor trauma through everyday activities such as mastication and oral hygiene, as well as during dental treatment, oral lesions appear to be extremely rare. In an effort to provide a detailed explanation of the oral manifestations of PG, a systematic search was conducted using medical databases. A total of 20 cases of PG with oral involvement were reported in the English and French literature. The objectives of this article are to present the pertinent diagnostic criteria and to discuss the differential diagnosis and therapeutic modalities.

Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) is a newly recognized provisional entity included in mature B-cell neoplasm in the latest 2016 World Health Organization Classification. It has a self-limited growth potential with a high predilection for oral cavities and occurs in age-related or iatrogenic immunodeficiency with indolent clinical courses. However, it shares histological features with EBV-positive diffuse large B-cell lymphoma (DLBCL), and this often leads to diagnostic challenges and controversies in patients with an oral EBV-positive B-cell neoplasm. The aim of this study was to better characterize and comprehend the pathophysiology of DLBCL and EBVMCU in the oral cavity. We conducted clinicopathologic and recurrent gene mutation analysis of 49 cases (14 EBV positive, 35 EBV negative), including cases diagnosed as DLBCL or B-cell lymphoproliferative disorders with high-grade morphology in the oral cavity. All EBV-positive cases matched the criteria of EBVMCU, with significantly earlier clinical stages than the EBV-negative group (P=.0006). Besides, histological analysis showed that all EBV-positive cases presented polymorphous features, whereas 91.4% (32/35) of the EBV-negative cases showed diffuse and monotonous proliferation (P<.0001). Furthermore, EBV-positive cases presented favorable clinical outcomes without disease-related death or recurrence. Gene mutation analysis (MYD88, CD79A, CD79B, CARD11, and EZH2) revealed that 33.3% (9/27) of EBV-negative cases harbored at least 1 gene mutation, whereas no gene mutation was observed in the EBV-positive group (0/11). These results suggest that oral EBV-positive B-cell lymphoid proliferation with polymorphous features often fulfill the criteria for EBVMCU, with clinicopathologically and genetically distinctive properties., (Copyright © 2017 Elsevier Inc. All rights reserved.)

We report a unique case of a potassium aluminum sulfate oral dissolution leading to palatal chemical necrosis and extensive chemical ulcers on the tongue. The patient, a 47-year-old white, blind male, denied using cocaine or other illegal drugs that could cause such lesions. His self-medication started as a treatment for a traumatic ulcerative lesion on the hard palate. After palatal perforation, he started another self-medication routine, mixing corticoid cream and tandrilax tablets with a gauze obturator. Our treatment comprised the removal of all chemical factors, a surgical debridement, and a prosthetic obturator to resolve the communication. The 1-year follow-up showed no complications., (© 2017 Special Care Dentistry Association and Wiley Periodicals, Inc.)

Background: Many medications used to manage multiple sclerosis (MS) affect oral health. This review aimed to identify the oral side-effects of the current drugs recommended in Australia to treat MS and make dental practitioners aware of the range of symptoms., Methods: The Australian Therapeutic Guidelines and the Australian Medicines Handbook were searched for medications used to treat MS. For each medication, the generic name, class, route of administration, dosage and drug company reported side-effects were extracted from the online Monthly Index of Medical Specialties (MIMs) database. Meyler's Side-effect of Drugs Encyclopaedia was used to identify any additional oral adverse reactions to medications used to treat MS., Results: Fourteen drugs were identified for the treatment of MS progression and 13 drugs for the treatment of MS symptoms. For these medications, 18 oral side-effects were documented: xerostomia was the most common, followed by dysgeusia, dysphagia, mouth ulceration and sinusitis. Anticholinergic drugs caused xerostomia while immunosuppressants resulted in more infection-related side-effects., Conclusions: Dental practitioners should be aware of the range of symptoms likely to be reported by this population. Clinicians are encouraged to continue providing dental care for their patients who develop MS and refer complex cases to specialists., (© 2017 Australian Dental Association.)

Background: This study investigated the effects of mesenchymal stem cell (MSC) sheet transplantation on healing of chemically induced oral ulceration in a rabbit animal model., Methods: Oral mucosal ulcers were induced by topical application of filter paper soaked with 70% acetic acid to the anterior gingiva and buccal mucosa of 12 New Zealand white rabbits. The animals were randomly assigned to two groups: with (treatment group, n = 6) or without (control group, n = 6) cell sheets applied to ulcers. Gross findings were sequentially evaluated, and histologic examination was performed on day 7., Results: Based on gross inspection, ulceration resolved before day 5 in the treatment group; however, in the control group, healing was incomplete on day 7. In the treatment group, the total area of the ulcer decreased significantly from day 2 to day 5 (P < 0.001) and from day 5 to day 7 (P = 0.020), whereas the area decreased significantly from day 5 to day 7 in the control group (P < 0.001). Histologic and immunofluorescence examination revealed full-thickness mucosa healing and complete basal cell coverage in the treatment group; in contrast, only partial healing was observed on day 7 in the control group., Conclusions: Cell sheet technology using MSC can be an alternative treatment for oral ulcerations in that it can decrease healing time without invasive properties., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

PURPOSE：To observe the effects of a non-thermal atmospheric pressure argon plasma jet on the healing time, and the levels of superoxide dismutase（SOD）and malondialdehyde（MDA）in oral mucosal ulcer of golden hamsters．METHODS： 56 golden hamsters were randomly assigned to 8 groups, one normal control group, one ulcer group, one natural healing group without any therapy, one iodine glycerin group, two argon groups (30 s, 120 s)and two plasma groups (30 s, 120 s)．24 hours after the last treatment, 4 hamsters from each group were sacrificed to detect SOD and MDA levels in the oral mucosal ulcer by spectrophotometry. The healing time in the remaining hamsters was observed continuously for 9 days after the last treatment．The data were analyzed with SPSS 22.0 software package. RESULTS：The healing time of the plasma groups was significantly shorter than the other groups (P=0.00). 24 h after the last treatment, there was no significant difference between the plasma groups and the normal contro1 group in SOD and MDA levels (P>0.05), SOD level in plasma groups was significantly higher than other groups (P=0.00), and MDA level in plasma groups was significantly lower than other groups (P=0.00). There was no significant difference between 30 s and 120 s plasma group in SOD and MDA levels (P>0.05)., Conclusions: Non-thermal atmospheric pressure plasma in certain dose can increase SOD level and decrease MDA level in ulcer tissues effectively, and reduce the healing time of oral ulcer in golden hamsters．.

Purpose: To evaluate the effect of low-intensity pulsed ultrasound（LIPUS） combined with triamcinolone acetonide on oral mucosal ulcer in syrian hamster in several ways, including healing time, contents of superoxide dismutase（SOD）and malondialdehyde (MDA)., Methods: Sixty syrian hamsters were randomly divided into 5 groups, including a baseline group (containing a normal baseline group and a model baseline group, n=6) and 4 experimental groups (LIPUS processing and drug use group, LIPUS group, drug group and a normal control group without any processing, n=12). Four experimental groups and model baseline group were given oxygen free radicals to model the oral mucosal ulcer. At 24 h after the last treatment, the healing time of ulcer, content of SOD and MDA were compared between each group. SPSS 20.0 software package was used for statistical analysis., Results: Compared with LIPUS group,drug group and control group, the healing time of oral mucosal ulcer in LIPUS and drug combined group was shortened. At 24 h after the last treatment, the activity of SOD showed that the LIPUS and drug combined group[(2.32±0.30) U/mgprot] were significantly higher than the model baseline group[(1.48±0.29) U/mgprot], the LIPUS group[(1.83±0.15) U/mgprot], the drug group[(1.76±0.25) U/mgprot] and control group[(1.71±0.18) U/mgprot] (P<0.05). The results of MDA content showed that the LIPUS and drug combined group [(8.17±0.21) nmol/mgprot] were significantly lower than the model baseline group[(9.41±0.22) nmol/mgprot], the LIPUS group[(9.00±0.44) nmol/mgprot], the drug group [(9.04±0.43) nmol/mgprot] and control group[(9.03±0.46) nmol/mgprot] (P<0.05). After oral mucosal ulcer healing, the activity of SOD and MDA showed that the LIPUS and drug combined group, the LIPUS group, the drug group and control group were not significantly different from the normal baseline group (P>0.05)., Conclusions: Low-intensity pulsed ultrasound combined with triamcinolone acetonide can effectively improve the activity of SOD and reduce the contents of MDA in ulcerated tissues, and therefore accelerate the process of ulcer healing．.

Competing Interests: Competing interests: None declared.

This case report describes the management of tongue and lip lacerations due to dystonia in a 1-year-old infant. A splint was given to raise the bite and prevent repeated trauma and aid in healing of the oral tissue. This paper highlights the importance of pediatric dentist's role in improving quality of patient care in an intensive care unit.

Background: Chorea acanthocytosis is an extremely rare neurodegenerative condition characterized by neuropsychiatric disturbances, movement disorders, neuropathy, seizures, and acanthocytosis. In this case report, the authors will present the management of the oromandibular movement disorders associated with this disease., Case Description: This case report describes the focal management of the severe orofacial manifestations associated with this condition. The therapeutic approach adopted to reduce the severe oromandibular movements, dysphagia, and the numerous oral ulcers was selective electromyography (EMG)-guided botulinum toxin application to the inferior head of the lateral pterygoid muscles and masseters. This would be applied to control severe and sudden oromandibular dystonia., Results: Through this procedure, the authors were able to reduce these severe oral manifestations, which had a major impact on the patient's quality of life, and temporarily improve vital functions, such as mastication, deglutition, and speech articulation., Conclusions: Electromyography-guided botulinum toxin application may be a useful tool in the multimodal management of this condition.

Postsurgical injury by teeth to oral mucosa (reconstructed by a flap) can lead to ulceration and subsequent infection at the reconstructed site. A prompt intervention by fabricating a specially designed prosthesis to deflect the reconstruction flap away from the occluding teeth has been described for the treatment of cheek biting in the present clinical report., (Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Aphthous ulcers are painful ulcerations located on the mucous membrane, generally in the mouth, less often in the genital area. Three clinical forms of aphthous ulcers have been described: minor aphthous ulcers, herpetiform aphthous ulcers and major aphthous ulcers. Many other conditions presenting with oral bullous or vesiculous lesions orulcerations and erosions can be mistaken for aphthous ulcers. Currently, treatment of aphthous ulcers is palliative and symptomatic. Topical treatments (topical anesthetics, topical steroids and sucralfate) are the first line therapy. Recurrent aphthous stomatitis (RAS) is defined by the recurrence of oral aphthous ulcers at least 4 times per year. RAS is often idiopathic but can be associated with gastro-intestinal diseases (i.e. celiac disease, inflammatory bowel diseases), nutritional deficiencies (iron, folates...), immune disorders (HIV infection, neutropenia) and rare syndromes. Behçet's disease is a chronic, inflammatory, disease whose main clinical feature is recurrent bipolar aphthosis. Colchicine associated with topical treatments constitutes a suitable treatment of most RAS. Thalidomide is the most effective treatment of RAS but its use is limited by frequent adverse effects. Oral ulcers can be related to a wide range of conditions that constitute the differential diagnoses of aphthous ulcers. Oral ulcers are classified into three main groups: acute ulcers with abrupt onset and short duration, recurrent ulcers (mainly due to postherpetic erythema multiforme) and chronic ulcers (with slow onset and insidious progression). Acute oral ulcers are due to trauma, bacterial infections (including acute necrotizing ulcerative gingivitis), deep fungal infection, gastro-intestinal (namely inflammatory bowel disease) or systemic diseases. Chronic oral ulcers may be drug-induced, or due to benign or malignant tumors. Every oral solitary chronic ulcer should be biopsied to rule out squamous cell carcinoma. A solitary palatal ulcer can be related with necrotizing sialometaplasia., (Copyright © 2016. Published by Elsevier Masson SAS.)

Mouth ulcers are a common complaint by patients, with individuals regularly presenting to primary care practitioners for diagnosis and treatment. The aetiology and pathogenesis of oral ulceration is, however, both varied and complex. This article highlights the importance of differentiating recurrent aphthous stomatitis (RAS) in otherwise healthy individuals from recurrent oral ulceration (ROU) secondary to known or unknown systemic disease. An overview of the diagnosis and management of such patients is provided as a framework to guide general dental practitioners' with clinical decision making on whether to treat or refer to secondary care.

The diagnosis and treatment of oral lesions is often challenging due to the clinician's limited exposure to the conditions that may cause the lesions and their similar appearances. While many oral ulcers are the result of chronic trauma, some may indicate an underlying systemic condition such as a gastrointestinal dysfunction, malignancy, immunologic abnormality, or cutaneous disease. Correctly establishing a definitive diagnosis is of major importance to clinicians who manage patients with oral mucosal disease. Some of these diseases are infectious; however, most are chronic, symptomatic, and desquamative. Treatment and management requires an understanding of the immunopathologic nature of the lesion. This review will address how to differentiate and diagnose varying types of oral ulcers and provide a treatment strategy., (©2015 Frontline Medical Communications.)

Objective: To compare the clinical efficacy between the combined acupuncture therapy of acupoint injection and fire needling and the oral administration of vitamin C and B2 as well as subcutaneous injection of transfer factor., Methods: One hundred and fifty-eight patients of recurrent oral ulcer (ROU) differentiated as heat accumulation in the heart and spleen were randomized into an observation group and a control group, 79 cases in each, one. In the observation group, Xinshu (BL 15), Pishu (BL 20) and Zusanli (ST 36) were selected for acupoint injection of shuang huanglian injection, 1 mL at each point, three times a week, for 2 weeks totally. Additionally, fire needling was applied to the ulcer lesion and peripheral mucosa, once a day, totally for 3 times. In the control group, vitamin C 100 mg and vitamin B2 20 mg were prescribed for oral administration, three times a day; and subcutaneous injection of transfer factor was applied, 2 mL (3 mg), twice a week, for 2 weeks totally. The score of symptoms and physical signs and the visual analogue scale (VAS) were observed before and after treatment, as well as the time of ulcer healing and ulcer recurrence in the patients of the two groups. The clinical efficacy was compared between the two groups., Results: The total effective rate was 92.4% (73/79) in the observation group, better than 77.2% (61/79) in the control group (P < 0.01). The differences in the score of symptoms and physical signs and VAS score before and after treatment were significant statistically in the observation group and the control group (all P < 0.01). The score of symptoms and physical signs and VAS score after treatment in the observation group were reduced significantly as compared with those in the control group (both P < 0.01). The time of ulcer healing in the observation group was earlier than that in the control group [(3.87 +/- 1.01) d vs. (6.22 +/- 0.53) d, P < 0.01]. The recurrence rate in the observation was lower than that in the control group [22.7% (17/75) vs. 50.0% (36/72), P < 0.01]., Conclusion: The combined therapy of acupoint injection and fire needling achieves the better efficacy on ROU compared with oral administration of vitamin and subcutaneous injection of transfer factor. This therapy has the good and quick effect of analgesia, relieves the relevant symptoms, shortens the time of ulcer healing and reduces the recurrence rate.

Oral ulcers are common and can have many causes, making diagnosis challenging. This article provides an overview of common oral ulcers and an algorithmic approach to establishing the correct diagnosis. Factors such as duration, pattern of recurrence, clinical appearance, mucosal location, and presence or absence of systemic symptoms are useful clues to determining an ulcer's cause.

Aims and Objective: To determine the type, accuracy and content of information available on the Internet regarding the treatment of oral ulcers., Method: The search engine Google was used to generate a list of top 100 websites about 'mouth ulcer treatment'. The websites were evaluated using the DISCERN instrument and the JAMA benchmarks. Whether the site displayed the Health on the Net (HON) seal was also recorded., Results: The search yielded 1,460,000 sites on the Google website. Of the top 100 sites a total of 54 sites were suitable for analysis due to duplicate links and non-functioning links. Of the websites analysed, 31.5% achieved all four JAMA benchmarks and 13% achieved only one benchmark. No website receiving the maximum mark on the overall score and six websites received the lowest overall score regarding the DISCERN instrument. The questions with the poorest response score were 'Does it describe how the treatment choices affect overall quality of life?' and 'Does it provide support for shared decision-making?'. Only 7.4% of the websites displayed the HON seal., Conclusion: Diverse information regarding the treatment of oral ulcers is available on the Internet with variable accuracy levels based on both JAMA benchmarks and DISCERN.

Oral mucositis (ulcer) is a serious and painful side effect for patients with head and neck cancer following radiation therapy. However, current clinical strategies cannot efficiently prevent the occurrence of oral mucositis. In this study, we investigated whether bone marrow-derived cells (BMDCs) prevented the occurrence and/or decreased the severity of radiation-induced oral mucositis. Fresh concentrated BMDCs from male C3H mice were transplanted intravenously into female mice after tongue irradiation. For 14 days postirradiation, the changes of body weight and the time courses of ulceration were observed. Until the ulcer reached maximum size (7 days postirradiation), macroscopic and histologic analyses of harvested tongues were performed to detect the behavior of donor BMDCs. Between 2 and 5 days postirradiation, BMDCs-transplanted mice showed more expression of stem cell markers (c-Kit, Sca-1) and EGFR and fewer apoptotic cells when compared with nontransplanted control mice (irradiation group). On day 7, there were fewer and smaller ulcers observed in the BMDCs-transplanted group. Tongues of these mice had preserved their epithelial thickness, and regenerative activities (blood vessels formation, cell proliferation) were higher than they were in the irradiation group. Fluorescently labeled BMDCs were not detected in tongue epithelium but rather in connective tissue (dermis) just below the basal cell layer. These findings suggest that exogenous BMDCs behave to reduce radiogenic oral mucositis in a paracrine manner., (© International & American Associations for Dental Research.)