Oral Microenvironment Research Articles

Promoting oral mucosal wound healing using a DCS-RuB2A2 hydrogel based on a photoreactive antibacterial and sustained release of BMSCs.

The high occurrence rate and difficulties in symptom control are listed as the major problems of oral mucosal disease by medical professionals. Following the development of oral mucosal lesions, the oral microenvironment changes, immunity declines, and continuous bacterial stimulation causes wound infection. Traditional antibacterial drugs are ineffective for oral mucosal lesions. To overcome this problem, a light-responsive antibacterial hydrogel containing sustained-release BMSCs was inspired by the trauma environment in the oral cavity, which is different from that on the body surface since it mostly remains under dark conditions. In the absence of light, the hydrogel seals the wound to form a barrier, exerts a natural bacteriostatic effect, and prevents invasion by foreign bacteria. Simultaneously, mesenchymal stem cells are presented, and the released growth factors and other substances have excellent anti-inflammatory and angiogenic effects, which result in rapid repair of the damaged site. Under light conditions, after photo-induced shedding of the hydrogel, RuB2A exerts an antibacterial effect accompanied by degradation of the hydrogel. Results in a rat oral mucosal repair model demonstrate that DCS-RuB2A2-BMSCs could rapidly repair the oral mucosa within 4 days. Sequencing data provide ideas for further analysis of the intrinsic molecular mechanisms and signaling pathways. Taken together, our results suggest that this light-responsive antibacterial hydrogel loaded with BMSCs can be used for rapid wound repair and may advance the development of therapeutic strategies for the treatment of clinical oral mucosal defects.

Medication-Related Osteonecrosis: Why the Jawbone?

Medication-related osteonecrosis of the jaw (MRONJ) has emerged as a complication of anti-resorptive medications. Despite its low incidence rate, this problem has gained attention in recent years due to its devastating consequences and lack of preventive strategy. The fact that MRONJ incidence has been exclusive to the jawbones, despite the systemic effect of anti-resorptive medications, could be a starting point to unravel the multifactorial pathogenesis of this condition. This review aims to negotiate the question of why the jawbone is more susceptible to MRONJ than other skeletal sites. Approaching the problem from this perspective could provide new directions for the prevention of MRONJ and expand our understanding of the unique oral microenvironment.

Evaluation of tumor-infiltrating T & B lymphocytes and their association and distribution in oral squamous cell carcinoma tumor microenvironment: An in vitro immunohistochemical study

The immune interaction between host immunity and the tumor microenvironment is complex, and a thorough understanding of tumor-infiltrating lymphocyte selection in oral cancer, including T and B cells, is urgently required. Within the tumor microenvironment, tumor cells escape immune surveillance and grow uncontrollably. The study examined the relationship and distribution of tumor-infiltrating T and B lymphocytes. Retrospective data of paraffin-embedded tissue samples of 47 primary oral squamous cell carcinoma (OSCC) cases were retrieved. Hematoxylin and eosin evaluation, along with all clinicopathologic data, were collected. Immunohistochemical CD3 and CD20 markers were used and evaluated for association and distribution in given OSCC cases. The intermediate type of inflammatory infiltrate was seen primarily in Well DIfferentiated Squamous cell Carcinoma grade and positive and negative lymph nodes. Compared with T-cell density, B-cell density showed an aggregate pattern rather than a scattered pattern, indicating a statistically significant association between T-cell and B-cell infiltrate. B-cell infiltrates were also found to have a statistically significant relationship with tertiary lymphoid structure. A strong, positive association and correlation exists between B- and T-lymphocyte infiltration in both the stroma and the invasive front. When compared with T-cell density, B-cell density is more predominantly in aggregates.

PH-activated antibiofilm strategies for controlling dental caries.

Dental biofilms are highly assembled microbial communities surrounded by an extracellular matrix, which protects the resident microbes. The microbes, including commensal bacteria and opportunistic pathogens, coexist with each other to maintain relative balance under healthy conditions. However, under hostile conditions such as sugar intake and poor oral care, biofilms can generate excessive acids. Prolonged low pH in biofilm increases proportions of acidogenic and aciduric microbes, which breaks the ecological equilibrium and finally causes dental caries. Given the complexity of oral microenvironment, controlling the acidic biofilms using antimicrobials that are activated at low pH could be a desirable approach to control dental caries. Therefore, recent researches have focused on designing novel kinds of pH-activated strategies, including pH-responsive antimicrobial agents and pH-sensitive drug delivery systems. These agents exert antibacterial properties only under low pH conditions, so they are able to disrupt acidic biofilms without breaking the neutral microenvironment and biodiversity in the mouth. The mechanisms of low pH activation are mainly based on protonation and deprotonation reactions, acids labile linkages, and H+-triggered reactive oxygen species production. This review summarized pH-activated antibiofilm strategies to control dental caries, concentrating on their effect, mechanisms of action, and biocompatibility, as well as the limitation of current research and the prospects for future study.

Understanding metabolic alterations after SARS-CoV-2 infection: insights from the patients’ oral microenvironmental metabolites

BackgroundCoronavirus disease 2019 is a type of acute infectious pneumonia and frequently confused with influenza since the initial symptoms. When the virus colonized the patient's mouth, it will cause changes of the oral microenvironment. However, few studies on the alterations of metabolism of the oral microenvironment affected by SARS-CoV-2 infection have been reported. In this study, we explored metabolic alterations of oral microenvironment after SARS-CoV-2 infection.MethodsUntargeted metabolomics (UPLC-MS) was used to investigate the metabolic changes between oral secretion samples of 25 COVID-19 and 30 control participants. To obtain the specific metabolic changes of COVID-19, we selected 25 influenza patients to exclude the metabolic changes caused by the stress response of the immune system to the virus. Multivariate analysis (PCA and PLS-DA plots) and univariate analysis (students’ t-test) were used to compare the differences between COVID-19 patients and the controls. Online hiplot tool was used to perform heatmap analysis. Metabolic pathway analysis was conducted by using the MetaboAnalyst 5.0 web application.ResultsPLS-DA plots showed significant separation of COVID-19 patients and the controls. A total of 45 differential metabolites between COVID-19 and control group were identified. Among them, 35 metabolites were defined as SARS-CoV-2 specific differential metabolites. Especially, the levels of cis-5,8,11,14,17-eicosapentaenoic acid and hexanoic acid changed dramatically based on the FC values. Pathway enrichment found the most significant pathways were tyrosine-related metabolism. Further, we found 10 differential metabolites caused by the virus indicating the body’s metabolism changes after viral stimulation. Moreover, adenine and adenosine were defined as influenza virus-specific differential metabolites.ConclusionsThis study revealed that 35 metabolites and tyrosine-related metabolism pathways were significantly changed after SARS-CoV-2 infection. The metabolic alterations of oral microenvironment in COVID-19 provided new insights into its molecular mechanisms for research and prognostic treatment.

Enhanced Corrosion Resistance and Local Therapy from Nano-Engineered Titanium Dental Implants

Titanium is the ideal material for fabricating dental implants with favorable biocompatibility and biomechanics. However, the chemical corrosions arising from interaction with the surrounding tissues and fluids in oral cavity can challenge the integrity of Ti implants and leach Ti ions/nanoparticles, thereby causing cytotoxicity. Various nanoscale surface modifications have been performed to augment the chemical and electrochemical stability of Ti-based dental implants, and this review discusses and details these advances. For instance, depositing nanowires/nanoparticles via alkali-heat treatment and plasma spraying results in the fabrication of a nanostructured layer to reduce chemical corrosion. Further, refining the grain size to nanoscale could enhance Ti implants' mechanical and chemical stability by alleviating the internal strain and establishing a uniform TiO2 layer. More recently, electrochemical anodization (EA) has emerged as a promising method to fabricate controlled TiO2 nanostructures on Ti dental implants. These anodized implants enhance Ti implants' corrosion resistance and bioactivity. A particular focus of this review is to highlight critical advances in anodized Ti implants with nanotubes/nanopores for local drug delivery of potent therapeutics to augment osseo- and soft-tissue integration. This review aims to improve the understanding of novel nano-engineered Ti dental implant modifications, focusing on anodized nanostructures to fabricate the next generation of therapeutic and corrosion-resistant dental implants. The review explores the latest developments, clinical translation challenges, and future directions to assist in developing the next generation of dental implants that will survive long-term in the complex corrosive oral microenvironment.

Biological Impact of the Ratio of E-Cigarette Liquid Base Constituents, Propylene Glycol and Vegetable Glycerin, on Primary Human Melanocytes

Oral cavity is the first site to encounter e-cigarette (EC) or tobacco smoke. Increased gingival pigmentation can lead to aesthetic concerns and hinder successful outcomes of gingival depigmentation procedures as well as lead to color alterations in patients with dental restorations. While the effects of tobacco smoke and nicotine in increasing pigmentation in the gingiva of the smoker have been well-documented, the effects of EC on pigmentation have not been explored. Due to large variations in e-liquids from different sources, this study focused on the effects of EC liquid base constituents, propylene glycol (PG) and vegetable glycerin (VG), which are a universal constituent of all e-liquids. Effects of PG and VG solutions mixed at different ratios (0/100, 20/80, 55/45, 80/20, and 100/0 % v/v) were examined using primary human melanocytes obtained from neonatal foreskin; this cell model is representative of the physiological model of gingival melanocytes and has been used in our previous study. Results showed significant concentration-dependent cytotoxicity for all groups, although mixtures with higher PG content showed higher cytotoxicity to cells as compared to those with VG. Melanogenesis was robustly activated by PG-containing mixtures with the greatest effect obtained for 80/20 PG/VG mixture as compared to other ratios, while VG by itself did not activate melanogenesis. The activation of melanin synthesis within cells was not correlated to intracellular tyrosinase activity as that was suppressed by PG at higher ratios. Morphological changes of a multidendritic phenotype were observed in cells exposed to all PG/VG mixtures, with markedly greater effects for groups with higher PG content. Taken together, the results of this pilot study demonstrate for the first time that EC base constituents possess the capacity to significantly activate melanogenesis in human melanocytes at nontoxic concentrations, with the dominant effect obtained at a PG/VG ratio of 80/20, indicative of a nonlinear response with increasing concentrations of PG. Moreover, further studies to address the impact of PG/VG with the addition of nicotine and the effects of different EC flavors are underway. Future studies to elucidate mechanisms of increased pigmentation as well as further investigate effects in melanocytes with the presence of other oral cell types and other components of the oral microenvironment such as saliva and bacterial flora are warranted. This research emphasizes the need to reconsider the regulation of EC base constituents PG and VG as different ratios of these compounds can cause differential effects.

Updates on immunological mechanistic insights and targeting of the oral lichen planus microenvironment.

Oral lichen planus (OLP) is a chronic immune inflammatory disease that is an oral potentially malignant disorder (OPMD), occurs in the oral mucosa and affects approximately 0.5% to 4% of the general population. There are usually five types of OLP: reticular/papular, plaque-like, atrophic/erythematous, erosive/ulcerative, and bullous. Furthermore, the chance of causing oral squamous cell carcinoma (OSCC) is 1.4%. Although the etiology of OLP is still unknown, accumulating evidence supports that immune dysregulation may play a vital role in the pathogenesis of OLP, especially the massive production of various inflammatory cells and inflammatory mediators. In this review, we focus on the relationship between OLP and its immune microenvironment. We summarize current developments in the immunology of OLP, summarizing functional cell types and crucial cytokines in the OLP immune microenvironment and the underlying mechanisms of key signaling pathways in the OLP immune microenvironment. We highlight the application potential of targeted immune microenvironment therapy for OLP.

Drug-loaded mucoadhesive microneedle patch for the treatment of oral submucous fibrosis.

Oral submucous fibrosis is a chronic, inflammatory and potentially malignant oral disease. Local delivery of triamcinolone to lesion site is a commonly used therapy. The existing methods for local drug delivery include topical administration and submucosal injection. However, in the wet and dynamic oral microenvironment, these methods have drawbacks such as limited drug delivery efficiency and injection pain. Therefore, it is urgently needed to develop an alternative local drug delivery system with high efficiency and painlessness. Inspired by the structure of band-aid, this study proposed a novel double-layered mucoadhesive microneedle patch for transmucosal drug delivery. The patch consisted of a mucoadhesive silk fibroin/tannic acid top-layer and a silk fibroin microneedle under-layer. When applying the annealing condition for the medium content of β-sheets of silk fibroin, the microneedles in under-layer displayed both superior morphology and mechanical property. The mechanical strength of per needle (0.071N) was sufficient to penetrate the oral mucosa. Sequentially, the gelation efficiency of silk fibroin and tannic acid in top-layer was maximized as the weight ratio of tannic acid to silk fibroin reached 5:1. Moreover, in vitro results demonstrated the double-layered patch possessed undetectable cytotoxicity. The sustained release of triamcinolone was observed from the double-layered patch for at least 7days. Furthermore, compared with other commercial buccal patches, the double-layered patch exhibited an enhanced wet adhesion strength of 37.74kPa. In addition, ex vivo mucosal tissue penetration experiment confirmed that the double-layered patch could reach the lamina propria, ensuring effective drug delivery to the lesion site of oral submucous fibrosis. These results illustrate the promising potential of the drug-loaded mucoadhesive microneedle patch for the treatment of oral submucous fibrosis.

The Bio-Aging of Biofilms on Behalf of Various Oral Status on Different Titanium Implant Materials.

The properties of titanium implants are affected by bio-aging due to long-term exposure to the oral microenvironment. This study aimed to investigate probable changes in titanium plates after different biofilm bio-aging processes, representing various oral status. Titanium plates with different surface treatments were used, including polish, sandblasted with large grit and acid etched (SLA), microarc oxidation (MAO), and hydroxyapatite coating (HA). We established dual-species biofilms of Staphylococcus aureus (S. aureus)-Candida albicans (C. albicans) and saliva biofilms from the healthy and patients with stage III-IV periodontitis, respectively. After bio-aging with these biofilms for 30 days, the surface morphology, chemical composition, and water contact angles were measured. The adhesion of human gingival epithelial cells, human gingival fibroblasts, and three-species biofilms (Streptococcus sanguis, Porphyromonas gingivalis, and Fusobacterium nucleatum) were evaluated. The polished specimens showed no significant changes after bio-aging with these biofilms. The MAO- and SLA-treated samples showed mild corrosion after bio-aging with the salivary biofilms. The HA-coated specimens were the most vulnerable. Salivary biofilms, especially saliva from patients with periodontitis, exhibited a more distinct erosion on the HA-coating than the S. aureus-C. albicans dual-biofilms. The coating became thinner and even fell from the substrate. The surface became more hydrophilic and more prone to the adhesion of bacteria. The S. aureus-C. albicans dual-biofilms had a comparatively mild corrosion effect on these samples. The HA-coated samples showed more severe erosion after bio-aging with the salivary biofilms from patients with periodontitis compared to those of the healthy, which emphasized the importance of oral hygiene and periodontal health to implants in the long run.

Altered dental plaque microbiota correlated with salivary inflammation in female methamphetamine users.

Poor oral health is the most immediate and overlooked hazard of methamphetamine abuse in humans. Previous studies have reported methamphetamine-associated alterations in saliva microbiota, but the cause of methamphetamine-induced alterations in the oral microenvironment remains unclear. The present study aimed to investigate the alterations in dental plaque microbiota in methamphetamine users, and to explore their relationship with local immune inflammation in the oral cavity. This may provide new ideas on the development of methamphetamine-related oral microenvironment changes. Questionnaires and samples were obtained from 30 female methamphetamine users and 15 sex- and age-matched healthy controls. Microbial profiles of supragingival dental plaque were analyzed using 16S rRNA gene sequencing. Inflammatory factors in saliva were measured using enzyme-linked immunosorbent assay. Methamphetamine users had worse oral self-evaluation. Compared with healthy controls, methamphetamine users showed no differences in oral dental plaque microbial diversity but exhibited differences in the relative abundance of several microbial taxa. At the phylum level, a higher abundance of Proteobacteria and a lower abundance of Firmicutes were detected in methamphetamine users. Moreover, function prediction using the MetaCyc database showed that 33 pathways were significantly upregulated in methamphetamine users; Only the glycolytic (Pyrococcus) pathway was enriched in the C group. Importantly, salivary inflammatory factors showed complex significant associations with bacterial genera in methamphetamine users. Specifically, the genus Neisseria was positively correlated with IL-17 levels in saliva, and both were high in methamphetamine users. In contrast, the genus Streptococcus, with a lower abundance, was positively correlated with lower IL-10 levels. Overall, This study is the first to provide evidence for a link between altered dental plaque microbiota and salivary inflammation in methamphetamine users. Further elucidation of the interactions between methamphetamine use and oral microenvironment would be beneficial for appropriate interventions to improve oral health.

Potential Role of Host Microbiome in Areca Nut-Associated Carcinogenesis and Addiction.

Areca nut (AN) is widely consumed all over the world, bringing great harm to human health and economy. Individuals with AN chewing are at high risk of cardiovascular disease and impaired immune system and metabolic system. Despite a growing number of studies having reported on the adverse effects brought by AN chewing, the exact mechanism of it is limited and the need for additional exploration remains. In recent years, the interaction between microorganisms, especially intestinal microorganism and host, has been extensively studied. AN chewing might disrupt the oral and intestinal microbiota communities through direct connect with the microbes it contains, altering PH, oxygen of oral and intestinal microenvironment, and disturbing the immune homeostasis. These mechanisms provide insights into the interplay between areca nut and host microbiota. Emerging studies have proposed that bidirectional interaction between polyphenols and intestinal microbes might play a potential role in the divergence of polyphenol, extracted from AN, among individuals with or without AN-induced cancer development and progression. Although some AN chewers have been aware of the harmful effects brought by AN, they cannot abolish this habit because of the addiction of AN. Increasing studies have tried to revealed that gut microbiota might influence the onset/development of addictive behaviors. Altogether, this review summarizes the possible reasons for the disturbance of host microbiota caused by areca nut chewing and clarifies the complex interaction between human microbiome and major constituents and the addiction and carcinogenicity of AN, tempting to provide novel insights into the development and utilization of it, and to control the adverse consequences caused by AN chewing.

Development and evaluation of osteogenesis and antibacterial properties of strontium/silver-functionalized hierarchical micro/nano-titanium implants

Promoting implant osseointegration while preventing infection is one of the major challenges in the development of dental implants. In this study, nano-needle-like structures were prepared on titanium by hot alkali treatment and then coated with uniform silver (Ag) and strontium titanate (SrTiO3) through magnetron sputtering. The results of ion release showed that the SrTiO3 outer coating reduced the release of Ag ions by 30% and 15% respectively on the 4th and 7th days, thus effectively improving the bioactivity of the Ag-modified substrates. In vitro experiments demonstrated that the Ag/SrTiO3-coated specimens (AH-Ti/Ag/Sr) had an excellent effect on the osteogenic differentiation of MC3T3-E1 cells and exhibited antibacterial function against Staphylococcus aureus and Escherichia coli (percentage of dead/total bacteria: ∼93% and ∼88%). Moreover, the in vivo results further confirmed that the Ag/SrTiO3 bilayer coating significantly promoted osteogenesis around the AH-Ti/Ag/Sr implant (the new bone volume and the number of trabeculae: 1.5 and 1.4 fold of the control group) and enhanced the bonding strength between implant and surrounding bone (about 1.9 fold of the control group). All these findings indicate that AH-Ti/Ag/Sr can substantially improve osteogenesis in complex oral microenvironment, and thus has potential applications in oral implantology.

The altered production and property of saliva induced by ingesting fermented food ingredients affect the oral microbiome composition in mice.

Oral functions are diverse and critical to human health. Therefore, insufficient secretion or poor quality of saliva, which is secreted into the oral cavity and plays various roles, could have a crucial influence on the oral microenvironment and be associated with systemic disease development. Here, we investigated the effects of food ingredients on saliva quantity and quality, including fermented ones. Through the in vitro submandibular glands' organ culture analyses, we found that "Yomo gyutto," fermented Japanese mugwort (Artemisia princeps), altered the expression of aquaporin-5, a water channel protein. We also found that Yomo gyutto increased saliva volume, along with the amount of α-amylase in mice, and caused changes in the oral microbiome composition of mice. These results suggested that by ingesting Yomo gyutto, we could directly and effectively manipulate the quantity and quality of saliva secreted from the salivary glands, potentially altering the oral microbiome composition for individual health.

Immunology of Oral Squamous Cell Carcinoma—A Comprehensive Insight with Recent Concepts

This review aims to understand the concept of oral cancer immunology through the notion of immune profiling, immunoediting and immunotherapy, and to gain knowledge regarding its application for the management of oral cancer patients. Oral cancer is an immunogenic tumor where the cells of the tumor microenvironment play an important role in tumorigenesis. Understanding the mechanism of these modulations can help design immunotherapeutic strategies in oral cancer patients. This article gives an overview of immunomodulation in the oral cancer tumor microenvironment, with concepts of immune profiling, immunoediting and immunotherapy. English literature searches via Google Scholar, Web of Science, EBSCO, Scopus, and PubMed database were performed with the key words immunology, tumor microenvironment, cells, cross talk, immune profiling, biomarkers, inflammation, gene expression, techniques, immunoediting, immunosurveillance, tumor escape, immunotherapy, immune checkpoint inhibitors, vaccines in cancer, oral cancer, and head and neck cancer. Original research articles, reviews, and case reports published from 2016-2021 (n = 81) were included to appraise different topics, and were discussed under the following subsections. Literature published on oral cancer immunology reveals that oral cancer immune profiling with appropriate markers and techniques and knowledge on immunoediting concepts can help design and play an effective role in immunotherapeutic management of oral cancer patients. An evaluation of oral cancer immunology helps to determine its role in tumorigenesis, and immunotherapy could be the emerging drift in the effective management of oral cancer.

Bismuth Quantum Dot (Bi QD)/Polydimethylsiloxane (PDMS) Nanocomposites with Self-Cleaning and Antibacterial Activity for Dental Applications.

In the oral microenvironment, bacteria colonies are easily aggregated on the tooth-restoration surface, in the manner of a biofilm, which usually consists of heterogeneous structures containing clusters of a variety of bacteria embedded in an extracellular matrix, leading to serious recurrent caries. In this contribution, zero-dimensional (0D) bismuth (Bi) quantum dots (QDs) synthesized by a facile solvothermal method were directly employed to fabricate a Bi QD/polydimethylsiloxane (PDMS)-modified tooth by simple curing treatment. The result demonstrates that the as-fabricated Bi QD/PDMS-modified tooth at 37 °C for 120 min not only showed significantly improved hydrophobic performance with a water contact angle of 103° and 115° on the tooth root and tooth crown, respectively, compared to that (~20° on the tooth root, and ~5° on the tooth crown) of the pristine tooth, but also exhibited excellent antibacterial activity against S. mutans, superior biocompatibility, and biosafety. In addition, due to the highly photothermal effect of Bi QDs, the antibacterial activity of the as-fabricated Bi QD/PDMS-modified tooth could be further enhanced under illumination, even at a very low power density (12 mW cm-2). Due to the facile fabrication, excellent hydrophobicity, superior antibacterial activity, and biocompatibility and biosafety of the Bi QD/PDMS-modified tooth, it is envisioned that the Bi QD/PDMS-modified tooth with a fascinating self-cleaning and antibacterial performance can pave the way to new designs of versatile multifunctional nanocomposites to prevent secondary caries in the application of dental restoration.

Huoxue Jiangtang Decoction Alleviates Type 2 Diabetes Mellitus by Regulating the Oral Microbiota and Food Preferences.

As a formula of traditional Chinese medicine (TCM), Huoxue Jiangtang Decoction (HJD) has positive effects on diabetes mellitus (DM) through improving of the metabolism of glycolipid and the function of β-cell. Hence, this research aims to explore the potential therapeutic effects of HJD on diabetes and reveal its underlying mechanisms. Diabetic rat models induced by high-fat diet (HFD) and streptozotocin (STZ) were included in this study. Following successful modeling, diabetic rats were treated with HJD, and then its therapeutic effects in eight weeks were evaluated. In addition to biochemical indicators, two-bottle preference tests were carried out to examine the rats' preferences for fat and sugar, and 16S rRNA gene sequencing was performed to disclose the differences of oral microbiota among groups. Finally, Pearson correlation coefficient was used to explore the correlation between oral microbiota and the preferences for fat and sugar. It was found that HJD significantly improved the levels of fasting blood glucose (FBG), glucose tolerance, and dyslipidemia. Additionally, HJD contributed to decreasing preferences for fat and sugar in diabetic rats, which plays an important role in food intake. Furthermore, HJD regulated the abundance, distribution, and structure of oral microbiota in diabetic rats, serving as one of the underlying mechanisms of its antidiabetic effects. Taken with other formulas, HJD functions to improve the metabolism of glycolipid and the function of β-cell by inhibiting preferences for fat and sugar, as well as regulating the oral microbiota of diabetic rats. Furthermore, a potential correlation between the oral micro-environment and preferences for fat and sugar in STZ-induced diabetic rats is likely to exist.

Advanced Drug Delivery Platforms for the Treatment of Oral Pathogens.

The oral cavity is a complex ecosystem accommodating various microorganisms (e.g., bacteria and fungi). Various factors, such as diet change and poor oral hygiene, can change the composition of oral microbiota, resulting in the dysbiosis of the oral micro-environment and the emergence of pathogenic microorganisms, and consequently, oral infectious diseases. Systemic administration is frequently used for drug delivery in the treatment of diseases and is associated with the problems, such as drug resistance and dysbiosis. To overcome these challenges, oral drug delivery systems (DDS) have received considerable attention. In this literature review, the related articles are identified, and their findings, in terms of current therapeutic challenges and the applications of DDSs, especially nanoscopic DDSs, for the treatment of oral infectious diseases are highlighted. DDSs are also discussed in terms of structures and therapeutic agents (e.g., antibiotics, antifungals, antiviral, and ions) that they deliver. In addition, strategies (e.g., theranostics, hydrogel, microparticle, strips/fibers, and pH-sensitive nanoparticles), which can improve the treatment outcome of these diseases, are highlighted.

Deformable Nanovesicle-Loaded Gel for Buccal Insulin Delivery.

Deformable nanovesicles (DNVs) have been widely used in oral mucosal delivery studies of biomolecular drugs. However, their development for oral mucosal preparations has been limited by their physical and chemical instability, the need for small oral volumes, and the complexity of the oral microenvironment. This study aimed to develop a more suitable buccal delivery system for DNVs with improved storage stability. Preliminary stability studies investigated different gel types, the effects of different hydrophilic gel matrices, and matrix temperature sensitivity using DNVs loaded with insulin-phospholipid complex (IPC-DNVs). A temperature-sensitive gel encapsulating IPC-DNVs (IPC-DNV-TSG) prepared with 2% w/v gelatin was stable at 4 °C for three months and maintained an excellent hypoglycemic effect. The delivery efficiency of IPC-DNVs and IPC-DNV-TSG was compared using a TR146 cell model, revealing that cell viability remained high. Cellular uptake was slightly lower for IPC-DNV-TSG than for IPC-DNVs, but total transport did not differ significantly between the two groups, which may have been related to the viscosity of IPC-DNV-TSG and the hydrophilicity, cell adhesion properties, and biocompatibility of gelatin. Moreover, neither IPC-DNVs nor IPC-DNV-TSG induced significant mucosal irritation in rabbit tongue tissue sections. The study findings demonstrate a promising method for possible use as oral mucosal delivery of peptide drugs.

Improvement in osteogenesis, vascularization, and corrosion resistance of titanium with silicon-nitride doped micro-arc oxidation coatings.

Titanium (Ti) implants have been widely used for the treatment of tooth loss due to their excellent biocompatibility and mechanical properties. However, modifying the biological properties of these implants to increase osteointegration remains a research challenge. Additionally, the continuous release of various metal ions in the oral microenvironment due to fluid corrosion can also lead to implant failure. Therefore, simultaneously improving the bioactivity and corrosion resistance of Ti-based materials is an urgent need. In recent decades, micro-arc oxidation (MAO) has been proposed as a surface modification technology to form a surface protective oxide layer and improve the comprehensive properties of Ti. The present study doped nano silicon nitride (Si3N4) particles into the Ti surface by MAO treatment to improve its corrosion resistance and provide excellent osteoinduction by enhancing alkaline phosphatase activity and osteogenic-related gene expression. In addition, due to the presence of silicon, the Si3N4-doped materials showed excellent angiogenesis properties, including the promotion of cell migration and tubule formation, which play essential roles in early recovery after implantation.