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Oral biofilm-associated infections are difficult to manage because of their polymicrobial nature, antimicrobial tolerance, and involvement in chronic oral diseases. This study evaluated the antimicrobial, anti-biofilm, and antioxidant potential of bioactive metabolites from the freshwater cyanobacterium Oscillatoria sp. PB602 against oral biofilm-associated pathogens and clinically relevant opportunistic colonizers implicated in complex oral infections. Methanolic extracts of Oscillatoria sp. PB602 were evaluated against oral pathogens and opportunistic colonizers, including Streptococcus mutans, Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa, and Candida albicans, using agar diffusion and Minimum Inhibitory Concentration (MIC) assay. Anti-biofilm activity was assessed by crystal violet staining and Confocal Laser Scanning Microscopy (CLSM), while bioactive metabolites were characterized using Gas Chromatography-Mass Spectrometry (GC-MS) and Fourier Transform Infrared Spectroscopy (FT-IR). Molecular docking analysis was performed to investigate potential interactions with biofilm-associated virulence proteins. The extract demonstrated concentration-dependent antimicrobial activity, with the highest inhibition observed against C. albicans (16 mm at 100 μg/mL). MIC analysis showed > 88% inhibition of mixed-species biofilms. Crystal violet assays revealed an 84% reduction in biofilm biomass, while CLSM confirmed ∼87% microbial cell death in mature biofilms at 2.5 × MIC. GC-MS identified fatty acid esters, including oleic acid derivatives, and FT-IR confirmed hydroxyl, carbonyl, and amine functional groups. Docking analysis indicated moderate binding affinity toward virulence-related proteins, with binding energies up to -5.8 kcal/mol. Oscillatoria sp. PB602 exhibited antimicrobial, anti-biofilm, and antioxidant activities against oral biofilm-associated pathogens and opportunistic colonizers, supporting its potential as a natural source of bioactive metabolites for oral healthcare applications and contributing to Sustainable Development Goal (SDG) 3 (Good Health and Well-being) through the advancement of preventive oral healthcare strategies.
Vitamin D3 status profoundly affects oral health and disease. Over the last decade, evidence has emerged that vitamin D3 activation can also occur in peripheral tissues. This narrative review was conducted to critically analyze the state of the art about the presence and activity of enzymes involved in the bioactivation of vitamin D3 in the oral tissues. A comprehensive literature search was performed in PubMed and Google Scholar. The search included articles published in English without any time limit. Keywords included but not limited to the combinations of: "vitamin D3", "25(OH)D3", "1,25(OH)2D3", "oral tissues", "megalin", "CYP27B1", "extrarenal", and "antimicrobial peptides". Further studies were identified by screening the reference lists of the relevant publications. Various vitamin D3 metabolites influence the inflammatory response and the production of antimicrobial peptides in various oral cells. The enzyme CYP27B1, which is responsible for the conversion of 25(OH)D3 into 1,25(OH)2D3 and its bioactivation, is present in various oral tissues and cells. The existence and physiological significance of local vitamin D3 activation in oral tissues remain unclear. Most of 25(OH)D3 is bound to the vitamin D-binding protein (DBP) and must be dissociated for activation. It is unclear whether and how this uncoupling occurs in oral tissue. Currently, there is rather indirect evidence that vitamin D3 could be bioactivated in oral tissues. Further studies on the local conversion of vitamin D3 to 25(OH)D3 and, subsequently, to 1,25(OH)2D3 in oral tissue, their regulation, and the role of free and bioavailable vitamin D3 metabolites are required.
This review summarizes the major metabolic processes underlying ferroptosis, elucidates its interaction mechanisms with oral infectious diseases, and outlines potential therapeutic targets for ferroptosis in oral infections, aiming to inform future treatment approaches. An electronic literature search was conducted in PubMed, Scopus, EBSCO, ProQuest, ScienceDirect, and Springer for studies on ferroptosis, periodontitis, pulpitis, periapical periodontitis, hand, foot, and mouth disease, Porphyromonas gingivalis, Fusobacterium nucleatum, Candida albicans and Enterovirus A71 published between 2010 and 2025. Ferroptosis is a newly discovered iron-dependent form of programmed cell death closely associated with a range of oral infectious diseases, including periodontitis, pulpitis, and apical periodontitis. It influences disease progression by regulating iron metabolism, lipid peroxidation, and the antioxidant defense system. Within the oral microenvironment, interactions among microorganisms, host cells, and immune modulators create an inflammatory milieu that further modulates ferroptosis. Crosstalk between ferroptosis regulatory pathways and other inflammatory regulatory pathways also occurs in this setting, playing a pivotal role in the induction of infectious diseases. Advances in mechanistic research are beginning to inform therapeutic strategies, and investigations into ferroptosis-targeted interventions for oral infection diseases are emerging. Ferroptosis is an important factor in the pathogenesis of oral infectious diseases and is a promising therapeutic target. Targeting ferroptosis pathway may provide a new approach for the treatment of oral infectious diseases. Further studies are needed to fully understand the mechanisms of ferroptosis in oral infectious diseases and to develop targeted therapies for clinical use.
Surface characteristics of titanium implants influence both bacterial colonization and host cell responses. However, the specific contribution of surface roughness within clinically relevant low-roughness ranges remains incompletely understood, particularly when isolated from other surface modifications. This study aimed to determine whether controlled variations in Ti6Al4V surface roughness Ra = 0.27-0.60 µm) induced by mechanical polishing are sufficient to influence early oral bacterial adhesion and osteoblast-like cell responses. Ti6Al4V samples were either manually polished or left unpolished, and surface roughness parameters were quantified by stylus profilometry. Biological performance was assessed using the early colonizer Streptococcus gordonii, the late pathogen Porphyromonas gingivalis, and MG-63 osteoblast-like cells. Bacterial adhesion and biofilm formation were evaluated by ATP bioluminescence, scanning electron microscopy (SEM), and RT-qPCR targeting adhesion-related genes. Osteogenic responses were measured through Alizarin Red staining, SEM, and RT-qPCR of osteogenic markers. Mechanical polishing reduced surface roughness from 0.60 to 0.27 µm without markedly altering peak profiles. For both bacterial species, adhesion levels, SEM biofilm morphology, and expression of adhesion-associated genes showed no significant differences between polished and unpolished surfaces. MG-63 cell adhesion, mineral deposition, and osteogenic gene expression were likewise unaffected by surface polishing. Within the low-roughness range tested, manual mechanical polishing of Ti6Al4V had no significant effect on early bacterial adhesion or osteogenic cell responses. This study highlights that polishing alone is insufficient to modulate early biological interactions at the implant interface, underscoring the need of advanced surface modification strategies to enhance implant biofunctionality.
This is an scoping review aimed at mapping the effects of Coriandrum sativum essential oil (CSEO) on oral fungal infection caused by Candida. Scoping review was conducted according to the methodology of the Joanna Briggs Institute and guided by the research question: What are the effects of CSEO on Candida in oral infection? Searches were performed in the following databases: SciELO, MEDLINE/PubMed, Web of Science, Scopus, Cochrane Library, the CAPES Journal Portal and Google Scholar. Publications in Portuguese, English, and Spanish were included, with no restrictions on date or population. MeSH/DeCS descriptors were used. Study inclusion and review development followed the PRISMA-ScR checklist. Out of the 245 studies identified, 30 were included. The findings revealed that the plant part, extraction method, environmental conditions, and genetic factors influenced variations in the phytochemical profile. Linalool was the major component extracted from seeds, fruits and flowers, while 1-decanol, decanal, 2E-decenol were predominant in leaf extracts. Although no clinical trial and in vivo experimental studies were found, in vitro experimental studies were identified, which demonstrated significant antioxidant, anti-inflammatory and antifungal activities, both against resistant strains and biofilms, in addition to synergistic effects with conventional antifungals and low to moderate toxicity. This review identified significant effects of CSEO against Candida, suggesting it is a promising candidate or potential adjuvant. However, further clinical and in vivo validation, with methodological standardization, to assess the safety, tolerability, and efficacy of this oil.
Oral leukoplakia (OLK) is an oral potentially malignant disorder with the potential to transform into oral squamous cell carcinoma. Our previous study demonstrated that azoxystrobin (AZOX), a natural product, reduced malignant transformation in a mouse model. Building on these findings, the present study aims to investigate the molecular mechanisms underlying AZOX-induced mitochondrial apoptosis in OLK. In vitro, mitochondrial complex III activity and adenosine triphosphate generation were assessed using a microplate reader. Mitochondrial reactive oxygen species levels were detected by flow cytometry and fluorescence microscopy, whereas mitochondrial membrane potential was evaluated using JC-1 staining. The apoptosis rate was quantified by flow cytometry. In tongue OLK tissues obtained from the animal model, the expression of mitochondrial apoptosis-related markers was examined by immunohistochemistry. In dysplastic oral keratinocyte cells, the expression of mitochondrial apoptosis-related markers was investigated by quantitative real-time polymerase chain reaction and western blot. In addition, the binding of AZOX to cytochrome b (Cyt b) was verified using cellular thermal shift assay. AZOX induced mitochondrial dysfunction and modulated the expression of mitochondrial apoptosis-related markers in both in vivo and in vitro models. Mechanistically, AZOX triggered mitochondrial apoptosis by inhibiting the Qo site of Cyt b in mitochondrial complex III. Direct binding of AZOX to Cyt b was further confirmed. AZOX induces mitochondrial dysfunction and apoptosis by targeting the Cyt b Qo site of mitochondrial complex III in OLK, thereby providing a mechanistic basis for its potential therapeutic application.
To map the existing evidence on the role of FAT family cadherins in craniofacial development, identify knowledge gaps, and inform future research directions in this field. Electronic searches were conducted in PubMed, Embase, Scopus, Web of Science Core Collection, and ProQuest Dissertations & Theses Global from their inception to January 2026, complemented by manual searches. Studies investigating FAT family cadherins in craniofacial development were included without restrictions on language or publication year. Search strategy and eligibility criteria were pre-determined based on the population, concept and context framework of the Joanna Briggs Institute. Eligible studies included case reports and original studies encompassing bioinformatics analyses, in vitro experiments, animal studies, and human genetic studies. Twenty-one studies were included, encompassing craniofacial bone formation, cranial suture development, upper lip and palate formation, and tooth development. Among the FAT family members, FAT4 was the most frequently studied (n = 12), followed by FAT1 (n = 7). None of the included studies investigated the role of FAT2 in craniofacial development. These cadherins exhibit prominent, stage-specific expression patterns during craniofacial morphogenesis, including the mesenchyme of the medial nasal processes, zygomatic-maxillary suture, and alveolar bone. Six case reports described four congenital syndromes that present with craniofacial abnormalities. The available evidence indicates that FAT family cadherins are substantially involved in craniofacial morphogenesis. However, important research gaps remain, particularly regarding their cooperative functions and precise spatiotemporal roles during craniofacial development, critical for understanding craniofacial anomalies. This review was registered at the Open Science Framework database (https://osf.io/wcxrj).
This systematic review aimed to synthesize and critically appraise molecular differences between oral squamous cell carcinoma arising in the background of oral submucous fibrosis (OSCC-OSMF) and OSCC without OSMF (OSCC-non-OSMF) across genomic, transcriptomic, proteomic, and immunohistochemical domains. A comprehensive literature search of PubMed/MEDLINE, Scopus, and Web of Science was conducted from database inception to November 2025 following PRISMA 2020 guidelines (PROSPERO: CRD420251152208). Human observational studies directly comparing molecular biomarkers between OSCC-OSMF and OSCC-non-OSMF were included. Risk of bias was assessed using the Newcastle-Ottawa Scale. Narrative synthesis was performed due to heterogeneity in study design, biomarkers, and analytical methods. Nineteen studies met inclusion criteria. Core carcinogenic pathways including p53 dysregulation, telomerase activation, and fibrosis-related mediators were largely comparable between OSCC-OSMF and OSCC-non-OSMF. In contrast, OSCC-OSMF consistently demonstrated enhanced epithelial-mesenchymal transition (EMT) and stemness signatures, increased genomic instability, and a markedly immunosuppressive tumor microenvironment characterized by regulatory T-cell predominance, PD-1/PD-L1 upregulation, and dendritic cell depletion. Paradoxically, OSCC-OSMF showed lower proliferative and angiogenic activity compared with OSCC-non-OSMF. Available evidence supports OSCC-OSMF as a fibrosis-conditioned clinic-molecular phenotype within the broader spectrum of OSCC. These findings highlight limitations of conventional prognostic markers and underscore the potential utility of immune, EMT, and genomic-related biomarkers for refined risk stratification and targeted therapy.
To establish an arecoline-induced preclinical model of oral submucous fibrosis (OSMF) and to investigate associated fibrotic and inflammatory mechanisms using in vitro and in vivo approaches. In vitro, hTERT and HaCaT cells were exposed to varying concentrations of arecoline to assess fibrotic markers, inflammatory cytokines, and reactive oxygen species (ROS), quantified by ELISA and qRT-PCR analysis. In vivo, Swiss albino mice were administered with arecoline (1 mg/kg for 25 days or 2 mg/kg for 15 days) via the sub-buccal route. OSMF induction was evaluated by body weight, mouth opening diameter estimation, cytokine expression, histopathological and immunohistochemical analysis, confirming fibrotic and inflammatory activation, characteristic of OSMF. In vitro, arecoline exposure induced dose-dependent increase in intracellular ROS generation, with elevated cytokines (IL-6, IL-13, TNF-α) and fibrosis-related genes (TGF-β1, Col1α2, Col3α1), and downregulated anti-fibrotic (IFN-γ) marker, indicating role of inflammatory activation and oxidative stress in inducing fibrosis. In vivo, arecoline-induced OSMF-like condition in mice showed reduction in body weight and mouth opening diameter. Histopathological findings also revealed epithelial atrophy, subepithelial hyalinization, and collagen accumulation in buccal and tongue tissues in arecoline-treated mice. Immunohistochemical analysis further confirmed overexpression of TGF-β1 and NF-κB in arecoline-treated mice, along with upregulation of TGF-β1, inflammatory cytokines (IL-6, IL-1β, TNF-α), and decline in IFN-γ, as determined by ELISA. The study demonstrates that arecoline induces OSMF-like condition in both cultured cells and mice, providing practical model for preliminary evaluation of potential anti-OSMF therapeutic agents by assessing fibrotic, inflammatory, oxidative stress markers, key molecular regulators of OSMF.
This systematic review with meta-analysis aimed to identify the main factors influencing the incidence of medication-related osteonecrosis of the jaws (MRONJ) in rodent models. A systematic search of experimental studies involving rat and mouse models of MRONJ was conducted across multiple databases up to April 2025. Risk of bias was assessed using Systematic Review Center for Laboratory animal Experimentation (SYRCLE) tool. Primary outcomes were the incidence of histological osteonecrosis and/or exposed bone or fistula in the oral cavity. A total of 119 studies were included, with 105 were eligible for meta-analysis. The pooled incidence of histological osteonecrosis was 28.60% (95% CI 20.24%-37.61%; I² = 90.3%) in rats and 23.81% (95% CI 8.24%-43.05%; I² = 88.6%) in mice. The overall incidence of bone exposure was 19.96% (95% CI 13.20%-27.50%; I² = 88.9%) in rats and 8.6% (95% CI 3.2%-15.5%; I² = 75.7%) in mice. Across both species, the MRONJ induction protocol and cumulative zoledronic acid (ZOL) dose were the main determinants of histological osteonecrosis, with higher incidences observed in ZOL plus tooth extraction protocols. In rats, the highest bone exposure rates occurred in ZOL-plus-extraction protocols associated with bone regularization, infection, or dexamethasone. In mice, greater bone exposure was associated with ZOL combined with cyclophosphamide or dexamethasone. Meta-regression models explained up to 78% of between-study heterogeneity. Statistically significant publication bias was detected only for bone exposure in rats. The induction protocol and ZOL dose are critical determinants of MRONJ incidence in rodent models.
This study investigated the effects of oral biotin supplementation on periodontal tissues using a standardized in vivo rat model under three conditions: periodontal health, untreated experimental periodontitis, and tissue response following mechanical periodontal instrumentation. One hundred and forty male Wistar rats received daily oral gavage with biotin (0.4 mL of a 5 mg/mL solution) or vehicle for 30 days. Experimental periodontitis was induced in 98 animals by ligature placement around the mandibular first molar. Of these, 70 animals remained untreated, while 28 underwent mechanical periodontal instrumentation 15 days after disease induction. The remaining 42 animals served as healthy controls. After euthanasia, hemimandibles were evaluated by microcomputed tomography, histological and histometric analyses, Picrosirius Red staining, and immunohistochemistry for tartrate-resistant acid phosphatase, osteocalcin, interleukin-1beta (IL-1β) and tumour necrosis factor-α (TNF-α). Biotin supplementation improved trabecular bone thickness, reduced bone porosity, and increased bone fill in the furcation region, particularly after mechanical periodontal instrumentation. Enhanced collagen fiber maturation was observed across all experimental conditions. Animals receiving biotin after instrumentation exhibited reduced osteoclastic activity, while increased osteocalcin expression was detected only in healthy periodontal tissues. In addition, biotin supplementation was associated with reduced immunolabeling of the pro-inflammatory cytokines IL-1β and TNF-α following mechanical periodontal instrumentation. In contrast, no significant differences in the inflammatory profile were observed under healthy conditions or during active experimental periodontitis. Biotin supplementation favorably modulated periodontal bone and connective tissue responses, with more pronounced effects following mechanical periodontal therapy.
This scoping review aims to examine the impact of food hardness on chewing physiological parameters in healthy children of different age groups. The study was conducted in accordance with the PRISMA guidelines for scoping review. A systematic search was performed in PubMed, Scopus, Web of Science, and Cochrane Library to identify studies published between 1983 and November 2024. Eligible studies examined in healthy children the association between food hardness and variables related to chewing function under experimental assessment conditions. Ten studies fulfilled the inclusion criteria. Increasing food hardness was associated with there is 1) an increase of the chewing cycles number and of chewing duration at the age of 9- 12 months 2) an increase in chewing cycle speed, vertical jaw displacements and muscle coordination at the age of 24-30 months 3) a change in the shape of the chewing cycle with greater muscular efficiency among children aged 3-12 years. However, most of the included studies adopted a cross-sectional and observational designs that used predominantly natural foods in the experiments. Furthermore, they covered a range of age groups that do not adequately represent the key stages of masticatory development and they did not comprehensively assess all relevant parameters of mastication at each age group. Food hardness affects masticatory parameters across all age groups. The available evidence remains limited and methodologically heterogeneous. Other studies are needed for improving the assessment and management of conditions characterized by impaired masticatory efficiency in children.
The present study aimed to investigate the effects of the systemic administration of LY404187, a positive allosteric modulator of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR), on swallowing function. Experiments were conducted on 78 male Sprague-Dawley rats anesthetized with urethane. Upper airway distention with continuous airflow and the topical laryngeal application of distilled water or capsaicin were used to induce swallowing, which was identified by electromyographic activity recordings from the mylohyoid and thyrohyoid muscles. We investigated the effects of systemic administration of LY404187 (0.25-5.0 mg/kg), an angiotensin-converting enzyme inhibitor (perindopril), a dopamine agonist (amantadine), or a benzodiazepine inverse agonist (S-8510) on swallowing initiation. An optimal concentration of LY404187 (1.0 mg/kg) significantly increased the number of airflow-induced swallows compared with before administration. However, LY404187 did not modulate the initiation of chemically induced swallows. The pre-administration of talampanel, an AMPAR antagonist, diminished facilitatory effects of LY404187 on airflow-induced swallows. Perindopril, amantadine, and S-8510 did not facilitate both mechanically and chemically induced swallows. These results suggest that LY404187 facilitates the initiation of mechanically induced swallows via AMPAR activation.
This study aimed to systematically review and meta-analyze the in vitro antifungal activity of herbal and conventional antifungals against Candida strains. In vitro studies were identified through PubMed, Embase, Scopus, and Web of Science up until May 2026. This review is registered with Prospero (CRD420251128404). Eligibility was determined using the Population, Intervention, Comparison, and Outcome (PICO) framework, with specific inclusion and exclusion criteria focused on in vitro antifungal investigations comparing herbal antifungals with conventional antifungals. The risk of bias was assessed using the modified Quality Assessment Tool for In Vitro Studies (QUIN Tool). A meta-analysis was performed, with the primary outcome measure being the ratio of means (RoM). The systematic review included twenty-five articles. Most studies showed different results in inhibition zones or minimum inhibitory concentrations between herbal and conventional agents. The meta-analysis indicates that certain herbal antifungals are equally effective as or more effective than conventional antifungals against Candida dubliniensis, Candida lusitaniae, and Candida tropicalis. While the efficacy of herbal antifungals for Candida albicans and Candida glabrata was modest, Piper betle L. demonstrated significant inhibitory potential. In contrast, conventional antifungals outperformed herbal antifungals against Candida krusei and Candida parapsilosis. This systematic review and meta-analysis highlight herbal medicine as a potential antifungal therapy for oral candidiasis, emphasizing the need for new strategies due to resistance to conventional antifungals.
To ensure the success of dental implant treatment, various factors must be considered, including osseointegration and systemic conditions. There is evidence in the literature that smokers may exhibit alterations in tissue healing, which can compromise the success of implant rehabilitation. Therefore, this study aimed to investigate the influence of nicotine on the protein profile of bone tissue around hydrophilic implants during the osseointegration process in rats. Bone tissue samples from the control and nicotine groups (n = 3 per group) were subjected to protein extraction, mass spectrometry, and bioinformatic analyses. Protein identification was performed using Proteome Discoverer 2.1 software and the SEQUEST algorithm, and the protein data were compared with those of a protein database of Rattus norvegicus obtained from UniProt. A total of 740 proteins were detected in both the control group and the nicotine-exposed group. Among them, the proteins biglycan, periostin and histone H4 were highlighted because of their higher abundance in the healthy implant group, while they were reduced in the nicotine-exposed group. Nicotine has the potential to alter the protein profile of bone tissue around hydrophilic implants during osseointegration, which may impair tissue remodeling and healing.
To explore the treatment effects of Decitabine (DAC) on Oral potentially malignant disorders (OPMDs) and understand the mechanism involved. Whole-genome bisulfite sequencing (WGBS) was performed on clinical OPMDs samples to identify differentially methylated genes, with SRY-box transcription factor 1 (SOX1) selected as a potential target. A rat model was established to evaluate therapeutic efficacy and biosafety of decitabine. In vitro experiments used dysplastic oral keratinocyte (DOK) cell line, with proliferation assessed by Cell Counting Kit-8 (CCK-8), apoptosis and cell cycle analyzed by flow cytometry, and pathway regulation verified by Western blotting (WB) and Quantitative real-time PCR (qRT-PCR). WGBS revealed aberrant DNA methylation in OPMDs, identifying SOX1 as a hypermethylated candidate gene. In vivo, decitabine inhibited malignant progression, with intermittent local injection showing optimal efficacy and biosafety. In vitro, decitabine suppressed DOK cell proliferation, induced G0/G1 phase arrest, and promoted apoptosis. Targeted bisulfite sequencing, qRT-PCR, and Western blotting indicated that decitabine reduces SOX1 methylation, thereby regulating the Wnt signaling pathway. Decitabine effectively inhibits malignant progression of OPMDs without apparent toxicity, potentially through SOX1 demethylation and subsequent Wnt pathway regulation, suggesting promising clinical value in preventing malignant transformation of OPMDs.
The regeneration of complex oral and maxillofacial tissues remains a significant clinical challenge. While stem cell-based therapies have shown promise, their clinical translation is impeded by safety concerns, immune rejection risks, and manufacturing standardization hurdles. Cell-free therapies utilizing extracellular vesicles derived from dental mesenchymal stem cells (DMSC-EVs) have therefore attracted increasing interest as a potential alternative strategy warranting systematic investigation. This narrative review, structured around a systematic literature search, critically analyzes the biogenesis, molecular cargo, and mechanistic basis of DMSC-EVs. We address the essential conceptual distinction between extracellular vesicles and whole conditioned medium, then examine specific applications in dental pulp, periodontal, and alveolar bone regeneration, with particular emphasis on emerging engineering strategies-including genetic modification, preconditioning, and biomaterial-based delivery systems-designed to overcome the limitations of native EVs. Inheriting the neural crest-derived regenerative potential of their parent cells, DMSC-EVs orchestrate tissue repair through three interconnected core mechanisms: immune microenvironment remodeling, angiogenesis-osteogenesis coupling, and neuroprotection. These pathways may interact functionally and could act synergistically in regenerative microenvironments. Emerging evidence from mineralization-related vesicle systems suggests that EVs may participate in hard-tissue biomineralization through vesicular trafficking of mineral-associated cargo; however, direct evidence for this mechanism in DMSC-EV-mediated oral regeneration remains limited. Engineering strategies show differential efficacy and clinical feasibility, with important tradeoffs to consider. DMSC-EVs represent a promising preclinical cell-free approach in oral regenerative medicine, though the path to clinical translation requires resolving urgent challenges in isolation standardization, quality control, scalable production, and regulatory classification. Specific benchmarking frameworks and reporting standards tailored to oral regeneration applications are proposed.
This study evaluated the effects of different combinations of Malva sylvestris on colony-forming unit (CFU) counts and microbiome in a microcosm biofilm, fibroblast cytotoxicity, and reduction of tooth demineralization. Samples were assigned to nine groups (n = 12): Malva sylvestris (2.5%); M. sylvestris + 5% xylitol; M. sylvestris + fluoride (0.0225%); M. sylvestris + xylitol + fluoride; xylitol; fluoride; M. sylvestris in a commercial product (Malvatricin Plus®); chlorhexidine (0.12%); and PBS. Plant metabolites were extracted by percolation. A microcosm biofilm model was applied, and from the 2nd to the 5th day, samples were treated with the solutions for 1 min. CFU counts were performed for Streptococcus mutans/S. sobrinus, Lactobacillus spp., and Candida albicans. Biofilm samples were analyzed by 16S rRNA gene sequencing (Illumina MiSeq) and QIIME. Cytotoxicity of M. sylvestris (0.08-2%) was assessed on human gingival fibroblasts, and demineralization was quantified by transverse microradiography. M. sylvestris (2%) showed lower cytotoxicity than chlorhexidine. The combination of M. sylvestris and xylitol reduced S. mutans counts in dentin biofilm by 1 log10/mL compared with PBS (p = 0.03), but not in enamel biofilm. Biofilms treated with M. sylvestris showed microbial communities similar to the negative control. However, the extract combined with fluoride and xylitol significantly reduced enamel demineralization compared with PBS (p < 0.0001), but not dentin demineralization. Malva sylvestris extract combined with fluoride and xylitol showed some antimicrobial and anticaries effects in vitro.
Enterococcus faecalis is the most prevalent pathogen in the persistent root canal infections. Especially, drug-resistant E. faecalis plays a major role in the root canal treatment failure. The present study aimed to find an effective natural therapeutic drug to combat the ampicillin-resistant Enterococcus faecalis (AREF) infection in the root canal system. The antibacterial effect of various phenolic compounds (curcumin, fisetin, hesperetin, morin, naringin, quercetin, rutin, and tannic acid) was screened against AREF, which was isolated from the infected root canals. The antibiofilm potential of tannic acid was assessed with CV staining, MTT assay, CFU counting, and CLSM analysis. The HR-SEM analysis of the tannic acid-treated AREF-infected root canals (a tooth model) was performed. Targeted interaction of tannic acid with biofilm-forming proteins such as ACE, DisA, ESP, and SrtC was investigated using Dock6. The biocompatibility of tannic acid was analysed on human RBCs and HGF cells. Tannic acid demonstrates excellent antibacterial effect against AREF. The ZOI and MIC values of tannic acid against AREF were 19.3 ± 0.57 mm and 80 µM, respectively. The 100% deadness of AREF infection was observed in the root canals at 1xMIC (80 µM) treatment after 7 days. Tannic acid demonstrated strong binding to biofilm-forming proteins, including ACE, DisA, ESP, and SrtC. The hemocompatibility and cytocompatibility of tannic acid were observed up to 150 µM and 100 µM, respectively. The present study recommends that tannic acid may be an efficient and safe natural phytocompound for combating AREF, thereby preventing root canal treatment failure.