Oral Ulcer Healing Research Articles

Magnesium metal-organic framework microneedles loaded with curcumin for accelerating oral ulcer healing.

Oral ulcers are a common oral mucosal disease that seriously affect the quality of life. Traditional drug treatments have shown unsatisfactory efficacy and potential adverse reactions. In this study, curcumin-loaded multifunctional magnesium metal-organic framework-embedded hyaluronic acid-soluble microneedles patches were developed to optimize treatment strategies for oral ulcers. This microneedles patch achieves efficient release of curcumin and Mg2+ in the ulcer through precisely targeted delivery and controllable release mechanism, significantly regulates inflammation, promotes cell migration and angiogenesis, and accelerates the ulcer healing process. At the same time, the synergistic effect of curcumin and gallic acid effectively alleviated oxidative stress, while the backplate ε-poly-L-lysine and needle tip Mg2+ jointly constructed an antibacterial barrier to effectively inhibit pathogens. Verification using an oral ulcer rat model showed that the microneedles patch exhibited excellent therapeutic effects. This not only opens up a new avenue for clinical oral treatment but also marks a breakthrough in nanobiomaterials science and drug delivery technology and heralds a broad prospect in the field of oral ulcer treatment in the future.

Preparation and characterization of mussel-inspired chitosan/polydopamine films and their feasibility for oral mucosa application

Oral mucosal lesions (OML), which represent a major public health issue worldwide, include any pathological changes in the oral mucosa, such as ulcers, pigmentation, and swelling. Due to its humid and dynamic complex environment, designing oral mucosal preparations poses significant challenges. Drawing inspiration from mussels, this study employed an eco-friendly one-pot strategy for the preparation of chitosan/polydopamine (CS/PDA) films. We demonstrated that CS-induced polymerization of dopamine monomers under acidic conditions, which might be attributed to the large number of hydrogen bonding sites of CS chains. PDA markedly enhances properties of the CS film and exhibits concentration dependence. At the concentration of 1 wt% PDA, the lap-shear strength and tensile strength of CS/PDA films reached 5.01 ± 0.24 kpa and 4.20 ± 0.78 kpa, respectively, indicating that the mucosal adhesion ability was significantly improved. In comparison with the single CS film, the swelling rate of CS/PDA film decreased by about 30 %. Rheological results also showed that the storage modulus returned to 93 % after cyclic large strain, while the single CS film only recovered to 73 %. Moreover, these films demonstrated good biocompatibility and enhanced oral ulcer healing in rats, providing a new and practical option for the local treatment of OML.

Multifunctional hydrogels for the healing of oral ulcers.

Oral ulcers are one of the most common oral diseases in clinical practice. Its etiology is complex and varied. Due to the dynamic nature of the oral environment, the wound surface is painful due to contact and wear, which seriously affects the quality of life of patients. Oral ulcers are often treated with topical drug therapy. Studies have shown that functional hydrogels play a positive role in promoting wound healing, showing unique advantages in wound dressings. In this paper, the causes and healing characteristics of oral ulcers are discussed in depth, and then the common treatment methods for oral ulcers are summarized and compared. Finally, the potential of functional hydrogels in the treatment of oral ulcers is discussed and projected through a review of the literature in recent years.

Mussel-inspired adhesive drug-loaded hydrogels for oral ulcers treatment

Oral aphthous ulcers are common mucosal lesions that cause pain and discomfort. There are diverse biomaterials and drug treatments for oral ulcers used in both research and clinical settings. However, the complex oral environment often results in low adhesion and short drug retention times, which lead to poor drug availability and treatment outcomes. In this study, a mussel-inspired adhesive hydrogel was developed by grafting catechol onto hyaluronic acid (C-HA), and dopamine was added for oxidative pre-polymerization to form modified hyaluronic acid (M-HA), which remarkably increased the adhesion of the hydrogels. Then, M-HA was interpenetrated into the gelatin methacryloyl (GelMA) network. Chlorhexidine gluconate (CHG) was then incorporated into the hydrogel to enhance its availability and therapeutic effect through its sustained-release capability. The GelMA/M-HA hydrogel demonstrated strong adhesion to wet tissues, antibacterial and anti-inflammatory properties, and good biocompatibility. In both rat oral ulcers and infected wounds, the adhesive hydrogel significantly accelerated the healing of the ulcers and infected wounds. These results indicated that this adhesive hydrogel offers a promising new strategy for the treatment of oral ulcers in clinical practice. Statement of significanceOral ulcers are a common and high-incidence mucosal condition that seriously affect people's daily lives, often making it difficult for patients to chew and speak. However, a dynamic oral environment with various types of bacteria influences drug availability and treatment effects in clinical settings. To address this challenge, an adhesive, mussel-inspired, drug-loaded hydrogel was constructed using natural macromolecules (hyaluronic acid and gelatin) with good biocompatibility. Chlorhexidine gluconate (CHG), with its broad-spectrum antibacterial activity, has been incorporated to synergistically promote oral ulcer healing. The splendid adhesion, antibacterial, and therapeutic effects of this hydrogel demonstrated a new strategy for treating oral ulcers.

A molybdenum sulfide based nitric oxide controlled release oral gel for rapid healing of oral mucosal ulcers

Oral mucosal ulcer is the most prevalent oral mucosal lesion, affecting over 25 % of general population. The current treatment regimens lack efficacy in addressing challenges such as wound bleeding, bacterial infection and inflammation on a continuous basis. Hence, a multi-functional oral gel (termed MPCST) with a long-acting duration is designed. It is based on a tannic acid-thioctic acid (TATA) supramolecular hydrogel which absorbs tissue exudate while exhibiting robust tissue adhesion properties. To form MPCST, TATA is loaded with MPCS, which are composed of polydopamine (PDA)-coated molybdenum disulfide (MoS2) nanoflakes (MoS2@PDA) with high photothermal conversion efficiency, nitric oxide (NO) precursor nitroprusside (SNP) and cerium oxide (CeO2) with high reactive oxygen species (ROS) scavenging rate. Upon exposure to 808 nm near-infrared (NIR) irradiation, MPCS rapidly heats up and releases NO to promote angiogenesis, while exhibiting strong ROS scavenging, antibacterial (including oral common Streptococcus mutans), and anti-inflammatory properties. Animal experiments show that the MPCST oral gel, composed of MPCS and TATA hydrogel, exhibits superior therapeutic efficacy compared to the commonly used dexamethasone patch.

Dampened inflammatory response in oral ulcer after topical therapy of adipose mesenchymal stem cell secretome

ObjectivesResearch has demonstrated that modulating inflammation can significantly accelerate the healing of oral ulcers. Our study focused on the adipose mesenchymal stem cell secretome (AdMSCS), which is rich in immunoregulatory molecules capable of dampening the immune response and interfering with inflammatory pathways. We assessed both inflammatory pathway expression and macrophage phenotypes at the sites of oral ulcers. MethodsWe induced oral ulcers in the inferior fornix mucosa of 20 healthy male Wistar rats (Rattus norvegicus). These subjects were treated topically with adipose MSC metabolite (AdMSCM) oral gel three times daily, for durations of 3 and 7 days. We performed immunohistochemical analyses to evaluate the expression of Toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB) p65 at the ulcer sites. Additionally, we assessed macrophage polarization by examining the ratio of M2/M1 macrophages, identified through CD68+Φ (M1) and CD163+Φ (M2) cells. Data were analyzed using one-way analysis of variance, followed by post-hoc Tukey's Honestly Significantly Difference test. ResultsApplication of AdMSCM oral gel significantly reduced the expression of TLR4 and NF-κB p65. This treatment also enhanced macrophage polarization towards the anti-inflammatory M2 phenotype at the ulcer sites (p < 0.05). ConclusionThe topical application of AdMSCM oral gel effectively modulates the inflammatory response, enhancing healing processes in the oral ulcer rat model. This suggests its potential utility as a therapeutic agent in managing oral ulcers.

Silk Fibroin Microneedles Loaded with Lipopolysaccharide-Pretreated Bone Marrow Mesenchymal Stem Cell-Derived Exosomes for Oral Ulcer Treatment.

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 Zn2+, 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 Zn2+ 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.

Antibacterial composite protein microneedle loaded with hypoxia-treated exosomes for oral ulcer healing

Oral ulcer treatment is challenging: various dressings have been developed, but they have poor efficacy. The efficacy of oral ulcer treatment depends on the local drug concentration; low drug concentrations result in slow wound healing. Therefore, the sustained release of active therapeutic ingredients from wound dressings with few administrations is promising. Hypoxic exosomes (Exos) can promote cell proliferation and angiogenesis. Further, silver nanoparticles (AgNPs) confer broad-spectrum antimicrobial effects. We prepared a light-cured composite microneedle (MN) patch based on bovine serum albumin methacryloyl (BSAMA) and methacrylic gelatin (GelMA) (the combination is denoted BG). Control, BG, BG@Exos, and BG@Exos&AgNPs were used to explore the therapeutic effects of hypoxic Exos and AgNPs on oral ulcers. In vitro experiments showed that BG@Exos&AgNPs MN patches effectively promoted cell migration, proliferation, and angiogenesis and significantly inhibited bacterial growth and expression of IL-2 and TNF-ɑ. We found that BG@Exos&AgNPs promoted the healing of oral ulcers in rats, demonstrated by rapid wound epithelial healing, downregulation of inflammatory factor expression, and increased macrophage polarization. Therefore, the designed BG@Exos&AgNPs MN patch is a valuable approach for treating oral ulcers.

Naltrexone accelerated oral traumatic ulcer healing and downregulated TLR-4/NF-kB pathway in Wistar rats

ObjectiveTo assess the effect of naltrexone on oral mucosal healing using a traumatic ulcer model DesignWistar rats (n = 112) received distilled water (control) or naltrexone (0.5, 10, or 50 mg/kg/day). Ulcers were induced on the buccal mucosa using a round skin biopsy punch (diameter 6 mm). Euthanasia was performed on days 1, 3, 7, and 14. Healing was assessed by ulcer area, histological scores, histomorphometric analysis (number of polymorphonuclears, mononuclears, and fibroblasts), and collagen percentage. Immunohistochemistry for TLR-2, TLR-4, NF-kB, and CD31 was evaluated. Nociceptive threshold was measured daily. ResultsThe 50 mg/kg group showed reduced ulcer area on days 1 (p < 0.001), 3 (p < 0.05), and 14 (p < 0.01). In this group, there was, on day 14, an increase in the percentage of reepithelization (p = 0.043) and collagen (p < 0.05), an increase in connective tissue maturation (p = 0.016), and on day 7 an increase in fibroblasts (p < 0.001). The 10 mg/kg dose reduced the ulcer area on day 1 (p < 0.001). The 50 mg/kg group showed lower expression of TLR-4 (p < 0.001) on day 1, NF-kB on days 1 (p < 0.05) and 14 (p < 0.05), and CD31 on day 14 (p < 0.05). The 0.5 and 10 mg/kg doses reduced TLR-4 expression on day 1 (p < 0.05; p < 0.01, respectively). Nociceptive threshold increased in the 50 mg/kg group (p < 0.01). ConclusionNaltrexone enhanced traumatic oral ulcer healing by reducing TLR-4/NF-kB signaling and promoting fibroblast proliferation and collagen deposition. Additionally, naltrexone reduced pain in rats.

Pedunculoside promotes oral ulcer healing in mice by upregulating STAT3 and Smad3

BackgroundPedunculoside (PE) is a pentacyclic triterpenoid saponin found in the dried barks of the Ilex rotunda Thunb. In traditional Chinese medicine, the juice extracted from various Ilex species is commonly used for treating inflammatory diseases. ObjectiveThis study aims to investigate the potential of PE in promoting the healing of oral ulcers in mice and to explore its possible mechanism. Materials and MethodsA mouse model of oral ulcer was established to evaluate the healing promotion effects of PE, and an in-vitro inflammatory cell model was established by using primary fibroblasts isolated from mouse oral mucosal tissue. Gene transcription and protein expression related to cell proliferation, migration, and collagen synthesis were measured. ResultsPE showed the highest cure rate of 85.7% for oral ulcers in mice within 7-days treatment. It significantly promoted cell proliferation and collagen secretion in fibroblast in-vitro model. PE also upregulated the gene transcription of Smad3, Col1a1 and Col3a1. Furthermore, PE antagonized the inhibitory effect of WP1066 on STAT3activation, but did not affect cell migration. ConclusionThis study demonstrates that PE has potential therapeutic effects in promoting oral ulcer healing in mice. The improvement was achieved by the increasing collagen synthesis through the upregulation of STAT3 and Smad3 in mucosa fibroblasts. These results provide a preliminary pharmacological work for developing PE as a potential treatment agent for oral ulcers.

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

ObjectiveMatrix metalloproteinase (MMP-1 and −9), Epidermal Growth Factor (EGF), and Transforming Growth factor (TGF)-β 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-β in the oral mucosa ulcer rat model treated with topical AdMSCMs. Materials and MethodsOral 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-β 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-β 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. ResultsA lower expression of MMP-1, MMP-9 in AdMSCMs group and higher expression EGF and TGF-β 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-β expression mean difference between day 3 and day 7 showed a significant difference compared to the control groups (p < 0.05) ConclusionsAdMSCMs oral gel may accelerate oral ulcer healing models by reducing the expression MMP-1, MMP-9, and increasing EGF and TGF-β expressions during the wound-healing process.

Efficacy of Topical Application of Chum Salmon (Oncorhynchus keta) Skin-derived Collagen Extracts in Improving Oral Traumatic Ulcer Healing

Background: Traumatic ulcer is a wound on the oral mucosa that often causes pain and impaired eating function. Healing of these wounds takes a long time and can interfere with an individual’s daily activities. One therapeutic approach that is being developed is the use of topical application of chum salmon skin-derived collagen extract. Collagen is the main component of the extracellular matrix and plays a major role in wound healing. The skin of chum salmon (Oncorhynchus keta) contains collagen that is effective for the treatment of wounds. Aim: The aim of this study was to evaluate the effectiveness of topical applications of chum salmon (O. keta) skin-derived collagen extracts in improving the healing of traumatic ulcers through analysis of neutrophil and macrophage numbers and collagen density. Materials and Methods: Twenty-four male Wistar rats were randomly divided into four groups consisting of six rats each. The labial mucosa of the lower lips of the rats was injured with heated amalgam stoppers to create oral traumatic ulcers. Group 1 was a control group; in Groups 2, 3, and 4, 25%, 50%, and 75% of collagen extracts from chum salmon (O. keta) skin were applied topically once a day for 7 days, respectively. The neutrophil and macrophage numbers were observed by hematoxylin and eosin staining. Masson’s Trichrome staining was used to analyze the collagen density. Data were analyzed using one-way analysis of variance and continued with post hoc least significant difference tests. Significance is considered if P &lt; 0.05. Results: The oral traumatic ulcers gradually healed until day 7. The number of neutrophils and macrophages was significantly decreased in the treatment groups, and collagen density was increased, compared to the control group (P &lt; 0.05). The decrease of neutrophil and macrophage numbers occurred significantly with the increased collagen extract concentrations (P &lt; 0.05). Collagen density also increased significantly with the increased collagen extract concentrations (P &lt; 0.05). Conclusion: Topical applications of chum salmon (O. keta) skin-derived collagen extracts accelerate the healing process of oral traumatic ulcers by decreasing neutrophil and macrophage numbers and increasing collagen density.

Multifunctional hyaluronic acid/gelatin methacryloyl core-shell microneedle for comprehensively treating oral mucosal ulcers

Oral ulceration is the most common oral mucosal disease. Oral mucosal ulcers are extremely painful, may interfere with eating and speaking, and potentially complicate systemic symptoms in severe cases. The humid and highly dynamic environment of the oral cavity makes local drug administration for treating oral mucosal ulcers challenging. To overcome these challenges, we designed and prepared a novel dissolving microneedle (MN) patch containing multiple drugs in a core-shell to promote oral ulcer healing. The MNs contained a methacrylate gelatin shell layer of basic fibroblast growth factor (bFGF), a hyaluronic acid (HA) core loaded with dexamethasone (DXMS), and zeolite imidazoline framework-8 (ZIF-8) encapsulated in the HA-based backplane. Progressive degradation of gelatin methacryloyl (GelMA) from the tip of the MN patch in the oral mucosa resulted in sustained bFGF release at the lesion site, significantly promoting cell migration, proliferation, and angiogenesis. Moreover, the rapid release of HA and, subsequently, DXMS inhibited inflammation, and the remaining MN backing after the tip dissolved behaved as a dressing, releasing ZIF-8 for its antimicrobial effects. This novel, multifunctional, transmucosal core-shell MN patch exhibited excellent anti-inflammatory, antimicrobial, and pro-healing effects in vivo and in vitro, suggesting that it can promote oral ulcer healing.

Adhesive hydrogel releases protocatechualdehyde-Fe3+ complex to promote three healing stages for accelerated therapy of oral ulcers

Oral ulcers can significantly reduce the life quality of patients and even lead to malignant transformations. Local treatments using topical agents are often ineffective because of the wet and dynamic environment of the oral cavity. Current clinical treatments for oral ulcers, such as corticosteroids, have limitations and side effects for long-term usage. Here, we develop adhesive hydrogel patches (AHPs) that effectively promote the healing of oral ulcers in a rat model. The AHPs are comprised of the quaternary ammonium salt of chitosan, aldehyde-functionalized hyaluronic acid, and a tridentate complex of protocatechualdehyde and Fe3+ (PF). The AHPs exhibit tunable mechanical properties, self-healing ability, and wet adhesion on the oral mucosa. Through controlling the formula of the AHPs, PF released from the AHPs in a temporal manner. We further show that the AHPs have good biocompatibility and the capability to heal oral ulcers rapidly. Both in vitro and in vivo experiments indicate that the PF released from AHPs facilitated ulcer healing by suppressing inflammation, promoting macrophage polarization, enhancing cell proliferation, and inducing epithelial-mesenchymal transition involving inflammation, proliferation, and maturation stages. This study provides insights into the healing of oral ulcers and presents an effective therapeutic biomaterial for the treatment of oral ulcers. STATEMENT OF SIGNIFICANCE: By addressing the challenges associated with current clinical treatments for oral ulcers, the development of adhesive hydrogel patches (AHPs) presents an effective approach. These AHPs possess unique properties, such as tunable mechanical characteristics, self-healing ability, and strong adhesion to the mucosa. Through controlled release of protocatechualdehyde-Fe3+ complex, the AHPs facilitate the healing process by suppressing inflammation, promoting cell proliferation, and inducing epithelial-mesenchymal transition. The study not only provides valuable insights into the healing mechanisms of oral ulcers but also introduces a promising therapeutic biomaterial. This work holds significant scientific interest and demonstrates the potential to greatly improve the treatment outcomes and quality of life for individuals suffering from oral ulcers.

Oral Aphthous-like Ulcers Response to Topical Therapy in Young Adult Woman with Beta-Thalassemia Intermedia

Background: Beta thalassemia may have some oral manifestations. Oral mucosa ulcer may be one of the oral manifestations of beta-thalassemia. The oral ulcer may resemble recurrent aphthous stomatitis (RAS). This current case report aims to present an aphthous oral ulcer as a manifestation in young adult women with beta-thalassemia. Case report: A 28-year-old woman complained of recurrent painful oral ulcers in the labial mucosa. She was diagnosed with beta-thalassemia intermedia three years before. The ulcer may take 3-4 weeks to heal completely. Intraoral examination revealed two yellowish ulcers, 5 mm and 10 mm, surrounded by an erythematous halo, regular margin on left lips mucosa, oral ulcer pain scale measured medium level by visual analogue scale (VAS). The oral aphthous-like ulcer was taken for diagnosis in this case. Topical treatment was given to the oral ulcer using chlorine dioxide gel three times daily. After 10 days, the oral aphthous-like ulcer was healed. Conclusion: An oral aphthous-like ulcer may be the oral manifestation in beta-thalassemia patients, and the oral ulcer may respond well to topical treatment commonly used in recurrent aphthous stomatitis (RAS) patients. Hence, it is important to recognize oral conditions as one clinical manifestation in beta-thalassemia patients and choose the appropriate treatment to accelerate oral ulcer healing.

The effect of biopolymer gel derived from sugarcane on healing of traumatic oral ulcers: an experimental study.

The extracellular polysaccharide (EPS) is produced by the bacterium Zoogloea sp. and plays a positive role in tissue repair. The purpose of this study was to clinically and histologically compare the effects of EPS in the healing of traumatic oral ulcers in rats with the effects of triamcinolone. Ulcers were induced in the oral mucous of 45male Wistar rats, divided into three groups: control group, treated with triamcinolone, and treated with biopolymer gel. In the clinical evaluation, we considered the weight variation of the animals and the size of the lesion area, at baseline and on treatment days 1, 3and7. The histological parameters evaluated were the type and intensity of the inflammatory infiltration, the presence of necrosis and foreign body granuloma and the degree of re-epithelialization of the lesion. The reduction of the lesion area was greater in the animals treated with EPS, with no difference in the intensity of the inflammatory infiltration between the groups on days 3 and 7 of treatment. The results suggest that topical application of EPS in traumatic oral ulcers of rats promotes faster repair than triamcinolone ointment, without increasing the intensity of inflammatory infiltration under the lesion.

Effects of a semi-interpenetrating network hydrogel loaded with oridonin and DNase-I on the healing of chemoradiotherapy-induced oral mucositis.

The aim of this study was to develop a semi-interpenetrating network (IPN) hydrogel system suitable for the oral environment, capable of controlled release of DNase-I and oridonin (ORI), to exert antimicrobial, anti-inflammatory, and reparative effects on chemoradiotherapy-induced oral mucositis (OM). This IPN was based on the combination of ε-polylysine (PLL) and hetastarch (HES), loaded with DNase-I and ORI (ORI/DNase-I/IPN) for OM treatment. In vitro studies were conducted to evaluate degradation, adhesion, release analysis, and bioactivity including cell proliferation and wound healing assays using epidermal keratinocyte and fibroblast cell lines. Furthermore, the therapeutic effects of ORI/DNase-I/IPN were investigated in vivo using Sprague-Dawley (SD) rats with chemoradiotherapy-induced OM. The results demonstrated that the IPN exhibited excellent adhesion to wet mucous membranes, and the two drugs co-encapsulated in the hydrogel were released in a controlled manner, exerting inhibitory effects on bacteria and degrading NETs in wound tissues. The in vivo wound repair effect, microbiological assays, H&E and Masson staining supported the non-toxicity of ORI/DNase-I/IPN, as well as its ability to accelerate the healing of oral ulcers and reduce inflammation. Overall, ORI/DNase-I/IPN demonstrated a therapeutic effect on OM in rats by significantly accelerating the healing process. These findings provide new insights into possible therapies for OM.

CD20 + cells blockage by rituximab delays wound healing in oral traumatic ulcers in rats

ObjectiveWound healing of oral traumatic ulcers (OTU) is strongly associated with cytokines and inflammatory cells, and the reduction of anti-inflammatory cells, such as lymphocyte B, may interfere with OTU repair. We aimed to evaluate the role of CD20 + cells in the healing process of OTU in rats. DesignWistar male rats were divided into four groups: a control group (treated with 0.1 mL/kg of saline) and three groups treated with anti-CD20 rituximab (RTX) at 2.5, 10, or 40 mg/kg 24 h before OTU production. The animals were weighed (day 0) and euthanized on days 3, 7, 14, and 21 after ulceration. With Blood cells (hematological analysis) and the traumatically induced ulcers were clinically measured. The mucosal samples were histologically (scores 0–4), histochemically (collagen assay (picrosirius)), histomorphometrically (cell counting), and immunohistochemically (CD20+, Tumor Necrosis Factor alpha(TNF-α), Interleukin(IL)− 1β, IL-6 and α-smooth-muscle-actin (α-SMA)) analyzed. ANOVA-1–2-way/Bonferroni, Kruskal-Wallis/Dunn, and correlation analyses were performed (GraphPad Prism 5.0, p < 0.05). ResultsRTX leads to leukopenia, lymphocytopenia, and neutropenia (p < 0.001), and high doses reduced the OTU area (p = 0.001), impaired histologic scores (p < 0.05), and delayed polymorphonuclear (p < 0.001) and mononuclear (p < 0.001) cells, and total (p = 0.011), type-I (p = 0.008), and type-III (p = 0.021) collagen. ConclusionRTX treatment reduced CD20+ cells in OTU (p = 0.001), TNF-α (p = 0.006), and α-SMA (p = 0.022) immunostaining and delayed IL-6 reduction (p = 0.006), with no influence in IL-1β immunostaining. CD20 + cell blockage by RTX reduced cell migration, acute inflammation, and wound healing in OTU.

Evaluation of clinical, histology, TNF-α, and collagen expressions on oral ulcer in rats after treatment with areca nut and chrysanthemum oral gel

Background: Areca nut (Areca catechu Linn.) is the seed of the fruit of the oriental palm that is commonly used among Southeast Asian communities. Chrysanthemum (Dendrathema grandiflora) is a flowering plant originating from East Asia and dominantly grows in China. Both of these plants have strong antioxidant activities. To investigate the mechanism of their wound healing activities, we prepared areca nut and chrysanthemum polyethylene oral gel and performed several in vivo assays using Sprague–Dawley rats. Methods: Sprague–Dawley rats were divided into six groups: Negative control group (rats with base gel treatment), positive control group (rats treated with triamcinolone acetonide), F1 (treatment with 20% areca nut:80% chrysanthemum), F2 (treatment with 50% areca nut:50% chrysanthemum), F3 (treatment with 80% areca nut:20% chrysanthemum), and normal group (without ulcer and treatment). Traumatic ulcers were performed on the buccal mucosa of all experimental animals that received topical oral gel and triamcinolone acetonide twice a day for seven days. The clinical and histological characteristics were analyzed and scored. Results: During the six days, the ulcerated area receded linearly over time and was completely cicatrized in F2, F3, and the positive control group (Dependent t-test, p&lt;0.05). There were significant increases in body weight in F2 and positive control groups. There were no significant differences between groups in histology examination (Kruskal Wallis test, p&lt;0.05). The moderate score of TNF-α levels was seen in F2 and positive control groups (ANOVA/Tukey test, p&lt;0.05). In the collagenases assay, a high concentration of areca nut (F3) induced the abundance of collagen during the ulcer healing process. Conclusions: The combination of areca nut and chrysanthemum extract in the oral gel can optimize the healing of traumatic oral ulcers in Sprague-Dawley rats through the increase of TNF-α and collagen deposition.

Preparation of capsaicin-loaded ultrafine fiber film and its application in the treatment of oral ulcers in rats

A drug-loaded diaphragm is an easy-to-use and effective drug delivery system that is often used to treat mouth ulcers. In this study, an ultrafine fiber film loaded with capsaicin was successfully prepared using the electrospinning technology. poly-l-lactic acid and gelatin were selected as the matrix materials to form the composite fiber, and trifluoroethanol was used as a co-solvent for poly-l-lactic acid, gelatin and capsaicin to prepare the spinning solution, which was simple to fabricate. The prepared fiber films were characterized based on their microscopic morphology and tested to derive their mechanical properties. Thereafter, the capsaicin release behavior of the film was investigated. In vitro experiments revealed certain anti-inflammatory and antibacterial abilities while animal experiments revealed that the capsaicin-loaded ultrafine fiber film could promote the healing of oral ulcers in rats. Healing of the tongue tissue in rats administered 10% capsaicin-loaded fiber film was found to be better than that in rats administered the commercial dexamethasone patch. Overall, this development strategy may prove to be promising for the development of oral ulcer patch formulations.