Insufficient skeletal repair is the primary threat of health span and lifespan in elders with increasingly vast global burden; yet, to date, the knowledge of resolving this crisis remains limited. In this study, we addressed the specific mechanisms underlying aging-associated poor bone repair, which are driven by the mitochondrial DNA structures mitochondrial G-quadruplex (mtG4). We found that mtG4 is spatiotemporal-wisely accumulated within Pdgfra+ periosteal mesenchymal stromal/stem cells (PPM) both in healthy and premature aging, which substantially increases cellular senescence and the degenerative alterations of PPM. By utilizing transgenic lineage tracking, PPM organoids formation, mitochondrial transgenic mutation, organoids transplantation, and serial cellular molecular investigations, we reveal that mtG4 in PPM restricts vital mitochondrial genes’ transcription to cause mitochondrial dysfunction, which utterly leads to severe mitophagy and cell senescence. These senescent PPM demonstrates impaired stemness and disrupted fate determination, finally phenocopying aging-associated poor bone repair. This study decodes the mitochondrial genomic reasons for insufficient bone repair during aging, which offers insights for developing cell-type- and disease-specific senolytic therapies in the future.

Periodontitis is among the most prevalent and challenging oral diseases worldwide. Effective intervention requires strategies that not only eliminate pathogens but also modulate the dysregulated oxidative microenvironment. Hydrogen (H2) therapy holds promise in periodontitis immunotherapy due to its exceptional safety profile and unique selective antioxidant properties. Here, we present a tailored biomaterial platform-Magnesium hydride (MgH2)-Poly(lactic-co-glycolic acid) (PLGA)@Oxygen-deficient titanium dioxide (TiO2-x)-Alginate core-shell microspheres (MTMs)-fabricated via coaxial electrostatic microdroplet technology for localized periodontitis therapy. This system provides rapid antibacterial activity together with sustained remodeling of the local tissue microenvironment. The MTMs achieve long-term antioxidant and anti-inflammatory effects through the synergistic sustained release of hydrogen molecules and Mg2+ ions (up to 7 days). Concurrently, the surface-etched TiO2-x particles embedded in the shell layer, exhibiting peroxidase-like catalytic activity, enable rapid antibacterial effects in the presence of low-level exogenous hydrogen peroxide. In vitro, MTMs attenuated oxidative stress in periodontal ligament stem cells and promoted lipopolysaccharide-stimulated macrophages to polarize from pro-inflammatory M1 toward reparative M2 phenotypes. In a rat periodontitis model, short-term treatment (1 week) reduced bacterial load, mitigated inflammation, and inhibited bone resorption, while long-term application (1 month) promoted bone repair and remodeling. These findings demonstrate that MTMs represent a powerful therapeutic platform for periodontitis and hold potential for broader biomedical applications.

Pulp necrosis remains a significant clinical challenge in dentistry, as current therapeutic approaches fail to achieve functional pulp regeneration. Extracellular vesicles (EVs), as crucial mediators of intercellular communication, offer new opportunities for regenerative strategies. In this study, we focus on CD24(+) human dental papilla cells (CD24(+) hDPCs), a functionally defined subpopulation previously characterized as having superior regenerative potential, and evaluate the regenerative potential of their derived EVs (CD24(+) EVs) in pulp-like tissue regeneration. CD24(+) EVs significantly enhanced the proliferation, migration, and osteo/odontogenic differentiation of human dental pulp stem cells (hDPSCs) and markedly promoted endothelial tube formation in vitro. In a treated dentin matrix (TDM)-based ectopic regeneration model, CD24(+) EVs increased cellular accumulation within the regenerated tissue and robust angiogenesis, inducing the formation of well-organized, highly vascularized pulp-like tissue with dense cellular architecture and positive DSPP expression. Together, these findings suggest that CD24(+) EVs concurrently enhance cell migration, odontogenic differentiation, and angiogenesis, and support a promising cell-assisted EV strategy grounded in functionally defined cellular subpopulations for pulp-like tissue regeneration.

Tooth morphogenesis is orchestrated by a complex interplay of signaling pathways and transcription factors that control cell proliferation, apoptosis, and differentiation, with the Wnt/β-catenin signaling pathway playing a pivotal role. However, the comprehensive regulatory mechanisms of Wnt/β-catenin signaling remain largely unclear. Smad7, a key antagonist of the TGF-β superfamily, is essential for maintaining tissue homeostasis and ensuring proper cellular function. Our previous study has demonstrated that Smad7 knockout in mice leads to impaired proliferative property of tooth germ cells, resulting in small molars. Here, we identified SMAD7 expression in human dental papilla and dental pulp, colocalized with β-CATENIN and cell proliferation-related proteins. RNA sequencing analysis revealed a significant reduction in Wnt signaling activity in Smad7-deficient mouse tooth germs. Using lentivirus transfection, we established SMAD7-knockdown human dental papilla stem cells, which manifested remarkably blunt proliferation rate, along with diminished Wnt signaling activity. In vivo transplantation investigations further revealed the indispensable role of SMAD7 in dentin formation. Mechanistically, we revealed that β-CATENIN interacts with P-SMAD2/3 and SMAD7 through co-immunoprecipitation and yeast two-hybrid assays. Inhibition of TGF-β pathway or disruption of SMAD7/β-CATENIN transcription factor complex formation potently impacted Wnt/β-catenin activities, indicating both direct and indirect regulatory mechanisms. These findings highlight the critical role of SMAD7 in the proliferation and differentiation of human dental stem cells, which could contribute to dental tissue regeneration and engineering.

Although mesenchymal stem cells (MSCs) are among the most promising cell types for regenerative medicine, the lack of mature “off-the-shelf” cryopreserved preparations limits their widespread clinical application. This represents a critical bottleneck and an often-underestimated complication of the cryopreservation process, which leads not only to significant reduction in viable cell yield but also to subtle yet consequential perturbations in therapeutic function. This review distinguishes itself by critically synthesizing recent advances through the lens of the integrated “vial-to-vein” pathway, emphasizing how cryopreservation-induced attrition of functional potency—particularly in immunomodulation and paracrine signaling—compromises clinical efficacy. We systematically analyze the evolution beyond conventional dimethyl sulfoxide (DMSO)-based media towards next-generation, bioinspired cryoprotectants and storage strategies designed to safeguard these critical biological attributes. We then review the cryopreservation effects on MSCs morphology, surface marker consistency, and multipotent differentiation as well as their fundamental immunomodulation. Subsequently, the review consider the efficiency of cryopreserved MSCs in different disease models like cardiovascular diseases — respiratory diseases and chronic kidney disease. Finally, we discuss the pivotal transition in quality control, arguing for a multi-pillar paradigm that integrates precise molecular identity testing with clinically relevant functional potency assays tailored to specific indications. Crucial in the pursuit of this integrated understanding is to ensure a set of consistent, reliable and coherent properties by which next-generation MSCs therapies can be evaluated. Yet correlating these in vitro metrics with clinical efficacy remains the single greatest hurdle.

In dental pulp regeneration, the ischemic microenvironment within the root canal severely compromises the survival and function of transplanted human dental pulp stem cells (hDPSCs). Here, we developed a PDMS-based core-shell oxygen-glucose delivery platform (P-C@P-G) that continuously released oxygen and glucose for up to 40 and 29 days, respectively, while minimizing peroxide-associated cytotoxicity through diffusion-controlled regulation without the need for exogenous enzymes. Under oxygen-glucose deprivation (OGD, 0.1% O2, glucose-free conditions) conditions, P-C@P-G improved cellular metabolic activity and enhanced hDPSC survival, proliferation, migration, and odontogenic differentiation. Compared with single-substrate supplementation, dual oxygen-glucose delivery produced greater improvements in hDPSC survival and differentiation. Transcriptomic and molecular analyses revealed alterations in TNF-α/NF-κB and Wnt/β-catenin signaling pathways following treatment. In vivo, P-C@P-G promoted pulp-like tissue regeneration, vascularization, and dentin sialophosphoprotein (DSPP) expression, resulting in greater pulp-like tissue formation and vascularization than the control group. Collectively, these findings demonstrated that sustained oxygen-glucose delivery effectively alleviated ischemia-associated metabolic insufficiency and revealed distinct contributions of oxygen and glucose to dental pulp regeneration.

Regeneration of the dentin-pulp complex is essential for tooth integrity and function. However, the inherent cell heterogeneity limits our understanding of lineage-specific subsets critical for efficient odontogenesis and regenerative outcomes. Here, we demonstrated that CD24+ human dental papilla cells (hDPCs) exhibit robust odontogenic differentiation capacity and drive coordinated regeneration of well-vascularized pulp and structurally integrated dentin tissues in both ectopic murine and preclinical in situ minipig models, significantly outperforming conventional dental pulp stem cells. Mechanistically, we delineate a BMP2/SIRT1 axis where elevated BMP signaling sustains SIRT1 expression and promotes mitochondrial metabolism and odontogenic capacity. Furthermore, BMP signaling induces VEGF expression, enhancing neovascularization via paracrine effects. CD24 is also a downstream marker of BMP signaling, though it does not directly mediate differentiation. Together, CD24+ hDPCs represent a regeneration-competent subpopulation that integrates mitochondrial metabolism and signaling crosstalk to enable coordinated dentin-pulp regeneration, representing a translationally relevant cell source for dental tissue engineering.

Continuous intracanal disinfection facilitates the complete elimination of residual pathogenic microorganisms and prevents the recurrence of root canal infections. Current prolonged disinfection strategies rely on calcium hydroxide or antibiotic pastes; however, these agents require thorough subsequent removal, which extends the treatment cycle and increases procedural complexity. Herein, we report a two-component irrigation system based on tannic acid (TA) solution and silver nitrate (AgNO3) solution that rapidly forms a long-lasting antibacterial coating (≤3 min) without the need for subsequent removal. Delivered via a dual-chamber syringe, this system generates a TA-Ag nanocoating in situ on the root canal wall through phenolic hydroxyl-Ag+ coordination and subsequent reduction, enabling long-term disinfection through sustained Ag+ release. Antibacterial assays demonstrated that the TA-Ag irrigation system achieved over 99% eradication of Enterococcus faecalis biofilms after a 3-min treatment and maintained inhibition of bacterial colonization on dentin for up to 2 weeks. In addition, TA molecules can chelate calcium ions from body fluid via phenolic hydroxyl groups, inducing calcium crystallization and promoting root canal wall remineralization. In vivo mouse wound infection models confirmed that the TA-Ag irrigant efficiently eliminates bacteria, attenuates inflammation, and accelerates tissue healing. Dental pulp stem cell experiments and oral mucosal contact tests verified its biocompatibility and safety. Collectively, this study presents a safe and effective root canal irrigation system capable of sustained intracanal disinfection and remineralization, showing great promise in root canal therapy and also other biomedical applications.

The components of dental implants, such as abutments and healing screws, are frequently exposed to the oral environment, making them susceptible to microbial contamination and potentially leading to peri-implantitis. Thorough and effective decontamination is crucial for preventing and treating peri-implantitis, but conventional methods cannot remove biofilms organic residues entirely. In our previous study, we developed a distinctive photocatalytic TiO2 coating on titanium substrates using plasma electrolytic oxidation. This study systematically evaluates the potential application of this coating on titanium implant components. This coating displayed a smooth surface morphology and was predominantly composed of Ti, O, and C elements. It exhibited excellent biocompatibility towards L929 fibroblast cells. Additionally, this coating displayed visible-light photocatalytic activity and effectively eliminated organic residues of the Porphyromonas gingivalis (P.g.) biofilm when exposed to visible light. After the photocatalytic treatment, the coating's surface hydrophilicity was significantly improved, while its morphology and roughness remained unaltered after mechanical scaling. This coating also exhibited remarkable corrosion resistance in a sodium chloride solution. The results demonstrated that this unique TiO2 coating, with visible-light photocatalytic activity, has great potential for application in implant components for deep decontamination.

Abstract Beige adipocytes that emerge during the peri-weaning period support sympathetic nervous system (SNS)-independent thermogenesis, yet the mechanisms governing this spontaneous beiging remain unclear. Here, by integrating transcriptomic profiling with adipocyte-targeted Ctnnb1 deletion in mice, we identify the canonical Wnt signaling as an endogenous brake on developmental beige thermogenesis. Peri-weaning inguinal fat from adipocyte Ctnnb1 knockout mice exhibits enhanced beige adipocyte biogenesis, with increased thermogenesis-related gene expression and mitochondrial oxidative capacity, which programs durable activation of adaptive thermogenesis and augmented whole-body energy expenditure into adulthood. Mechanistically, suppression of Wnt/β-catenin signaling induces a non-canonical Wnt5a-Ca 2 ⁺-AMPK axis that promotes triglyceride lipolysis and subsequent PPAR-driven fatty acid oxidation, thereby fueling mitochondrial respiration. Genetic or pharmacological disruption of this axis blunts thermogenic responses induced by β-catenin inhibition in both murine and human subcutaneous adipocytes, indicating that Wnt5a-Ca 2 ⁺-AMPK axis is required for the cell-autonomous activation of beige fat. These results reveal Wnt/β-catenin signaling as a developmental constraint on beige adipocyte formation and suggest an SNS-independent route to sustainably raise energy expenditure and improve metabolic health.

In periodontitis patients, periodontium inflammatory levels may remain even after systematic treatment, impeding efficacy of stem cell therapy. This study aimed to compare periodontal parameters and gingival crevicular fluid (GCF) and serum inflammatory profiles among healthy individuals, pre- and post-treatment periodontitis patients, and based on the data, describe the post-treatment “micro-inflammation” in periodontium of periodontitis patients. Ten healthy individuals (group H) and twenty-three periodontitis patients (group P) were included. Group P participants received full-mouth non-surgical periodontal treatment at baseline, and were followed up 4 and 12 weeks later. The GCF and serum samples were collected and periodontal clinical parameters were recorded. Seven inflammatory markers in the samples were assessed using enzyme-linked immunosorbent assay, including lipopolysaccharides (LPS), tumor necrosis factor-alpha (TNF-α), interleukins (IL)-6, IL-1β, Matrix metalloproteinase-8 (MMP-8), Interferon-gamma (IFN-γ) and IL-17 A. The amounts of TNF-α, IL-1β, IL-6, IL-17 A, MMP-8 and LPS in periodontitis patients’ GCF decreased significantly both 4 and 12 weeks after treatment (p < 0.05), while still higher than healthy individuals (p < 0.05); strong positive correlations were shown between these biomarker amounts in GCF and clinical parameters (P < 0.05), such as pocket depth and clinical attachment loss. Amounts of IFN-γ were similar between periodontal patients after treatment and healthy individuals. When measured with concentrations, LPS and TNF-α decreased after treatment (P < 0.05) and remained higher than group H (P < 0.05); IL-1β and MMP-8 in group P did not change significantly after treatment and were similar to those in group H. No biomarker in serum showed meaningful differences. Low-grade and sustainable inflammation in the post-treatment periodontium continues, which was termed “micro-inflammation”. The amounts of TNF-α, IL-1β, IFN-γ, IL-6, IL-17 A, MMP-8 and LPS in GCF can be used to describe characteristics of microinflammation, serving as reference for stem cell therapy on periodontal regeneration. This study was registered at Chinese Clinical Trial Registry (ChiCTR; registration number: ChiCTR2400088098, registration date: Aug 12, 2024).

The dental papilla (DP) is essential for the development of dentin and pulp. The extensive cellular heterogeneity within the DP is a critical factor underlying the complex and precise formation of dental structures during odontogenesis. However, the critical cell types within human DP that play essential role in tooth development and regeneration remain largely uncharacterized. In this study, we analyzed the heterogeneity of human DP cells using single-cell sequencing and identified Gliomedin (GLDN)+ DP stem cells (DPSCs) were a group of progenitors at an early stage of tooth development and play a key role in the development of pulp and dentin. GLDN+ DPSCs strategically accumulate in human DP tissue near the interface of the newly formed dentin or pulp. Functional assays demonstrated that GLDN+ DPSCs exhibited enhanced self-renewal, migratory capacity, and odontogenic differentiation potential in vitro compared to GLDN- DPSCs. Moreover, GLDN+ DPSCs effectively induce the migration and tube formation of endothelial cells, which are essential for tooth development. The ectopic dental pulp regeneration model confirmed that GLDN+ DPSCs can regenerate a vascularized dental pulp structure with an odontoblast layer in vivo. Given their functional capabilities, this population of cells has been designated as GLDN+ odontogenic stem cells (OSCs). Mechanistically, GLDN is essential for maintaining the phenotype and function of GLDN+ OSCs through BMP5 signaling via autocrine and paracrine mechanisms. In conclusion, this study identifies a previously uncharacterized essential subpopulation of OSCs essential for dental pulp development and regeneration.

Periodontitis, characterized by progressive alveolar bone resorption and periodontal defect formation, remains a major clinical challenge driven by bacterial infection and a dysregulated inflammatory immune microenvironment. Neutrophils, as the predominant innate immune cells, accumulate at infected sites to eliminate microbes but concurrently suppress osteoblast function, thereby impairing bone formation and accelerating alveolar bone loss. Lipopolysaccharide-preconditioned dental follicle stem cell-derived small extracellular vesicles (L-DFSC-sEV) exhibit potent immunomodulatory activity, facilitating the clearance of proinflammatory neutrophils and attenuating neutrophil hyperactivation, and reshaping the periodontal immunoregulatory microenvironment. However, the therapeutic efficacy of sEV is often hindered by the hostile infectious and inflammatory environment, as well as the lack of an appropriate delivery system tailored to periodontal conditions. To overcome these limitations, we developed a multifunctional, dynamically cross-linked hydrogel comprising gelatin, oxidized chondroitin sulfate, and epigallocatechin gallate at physiological pH, which encapsulates L-DFSC-sEV (L-DFSC-sEV@GCSE). This hydrogel exhibits excellent tissue adhesion, self-healing capability, antibacterial activity, and immunoregulatory properties, thereby creating a favorable microenvironment for sustained sEV release. In a rat periodontal defect model, L-DFSC-sEV@GCSE markedly enhanced sEV retention and delivery, effectively controlled infection and inflammation, modulated the osteoimmune microenvironment, and significantly promoted periodontal tissue regeneration.

Sclerotomal progenitors derived from pluripotent stem cells hold promises for modeling skeletal development and recapitulating the perinatal marrow niche that may provide insights into hematopoietic niche formation and immune regulation. Current strategy to derive mouse sclerotomal progenitors suffered from low differentiation efficiency and heterogeneous cell progenies. Here, we developed a fast and efficient strategy to generate sclerotomal progenitors by accelerated induction from primitive streak (PS) through modulating BMP and SHH signaling, achieving an 86.9% differentiation efficiency. Moreover, the resulting progenitors showed similar global gene expression profiles to those of the primary sclerotome, possessed strong osteochondral bipotential, and could recapitulate key features of endochondral ossification upon micromass-mediated osteogenic induction, including perinatal bone marrow (BM)-like niches regeneration. Our findings underscore accelerated sclerotomal induction from the primitive streak as an efficient strategy to derive sclerotomal progenitors for skeletal modeling and BM niche bioengineering.

Diabetic wounds are characterized by a persistent pathological imbalance between infection and regeneration, in which bacterial colonization and impaired tissue repair synergistically hinder the healing process. However, most existing wound dressings focus on a single therapeutic function, limiting their capacity to orchestrate both antimicrobial defense and tissue regeneration within the multifactorial wound microenvironment. Inspired by the spatially hierarchical architecture of natural honeycombs, we developed a biomimetic bidirectional membrane (PYS) fabricated via a breath figure patterning technique and biomass-derived polyester materials to achieve integrated structural and functional stratification. The dense and smooth outer layer serves as an effective physical antimicrobial barrier, while the inner layer features a downward-opening honeycomb structure that enables high-efficiency loading and sustained release of epidermal growth factor (EGF), providing a favorable three-dimensional microenvironment for cell migration and angiogenesis. In a diabetic mouse wound model, PYS-EGF significantly suppressed bacterial adhesion, promoted neovascularization, and accelerated wound closure. This study demonstrates that synergistic integration of structural biomimicry and functional stratification can achieve coordinated antimicrobial and regenerative effects in diabetic wounds, offering a promising strategy for the design of next-generation wound healing materials.

Oral Candida albicans (C. albicans) infections remain a persistent clinical challenge due to rising antifungal resistance and the systemic toxicity associated with conventional systemic oral therapies, particularly in immunocompromised patients. To address these limitations, we developed a dual-synergistic buccal composite (Gel/AbA/MH@PDA) by integrating the natural cyclic depsipeptide antifungal Aureobasidin A (AbA) with magnesium hydroxide (MH) as an alkaline modulator, both of which were incorporated into a polydopamine (PDA)-coated gelatin matrix. The PDA-coated composite exhibited enhanced stability under humid conditions and enabled sustained AbA release over 7 days while providing PDA-associated antioxidant activity. MH dissolution maintained a local pH of approximately 9 for up to 5 days, establishing a sustained mildly alkaline microenvironment. The combination of MH and AbA exhibited enhanced antifungal activity compared to either component alone, reducing C. albicans viability by 84.8%. In vitro, the composite significantly downregulated pro-inflammatory cytokines IL-6 and TNF-alpha by 68.3% and 72.5%, respectively, in LPS/C. albicans-stimulated models, promoted macrophage M2 polarization, and demonstrated excellent biocompatibility, with over 95% cell viability confirmed by CCK-8 and Live/Dead assays. In immunosuppressed mouse models, buccal administration achieved 97% fungal clearance and markedly reduced mucosal inflammation scores, outperforming the conventional treatment (oral fluconazole administration and NaHCO3 mouthwash). Collectively, this multifunctional buccal device integrates targeted antifungal activity, pH microenvironment modulation, and immunoregulatory effects, offering a localized therapeutic strategy that represents an initial step toward clinical translation for oral candidiasis. To our knowledge, this represents the first study to establish a sustained and localized mildly alkaline microenvironment for the treatment of oral candidiasis, providing new insights into therapeutic modalities for oral candidiasis.

Tooth loss remains a major unmet clinical challenge, and current prosthetic approaches cannot restore the biological complexity, sensory function, or regenerative capacity of natural teeth. Recent progress in stem cell biology, developmental engineering, and regenerative biomaterials has opened new possibilities for biological tooth regeneration. This review integrates advances across three major research domains that together define the current landscape of translational regenerative dentistry. First, we discuss stem cell-based, scaffold-guided strategies for tooth regeneration. These approaches combine dental and nondental stem cells, including DPSCs, SCAPs, PDLSCs, SHED, and iPSC-derived lineages, with bioactive materials such as HA/TCP ceramics, dentin-derived extracellular matrix scaffolds, and natural or synthetic polymers to promote odontogenic differentiation, vascularization, and periodontal attachment. Second, we summarize emerging tooth organoid and bioengineered tooth germ technologies that recapitulate epithelial–mesenchymal interactions and enable controlled reconstruction of dentin–pulp and periodontal compartments for modeling human odontogenesis. Third, we highlight molecular regulation-driven therapeutic strategies, focusing on the modulation of Wnt, BMP, FGF, TGF-β, and USAG-1 pathways to stimulate endogenous tooth regeneration and correct developmental defects. Despite marked progress, challenges remain, including stable neurovascular integration, optimization of stem cell–material crosstalk, precise control of spatiotemporal signaling, and long-term functional stability in vivo. Finally, we outline future directions involving smart biomaterials, gene- and protein-based molecular targeting, organoid-guided regeneration, and iPSC-enabled personalized therapies, which may further accelerate the clinical translation of stem cell-based tooth regeneration.

Introduction:Oral squamous cell carcinoma (OSCC) is a highly aggressive malignancy of the oral epithelium, marked by a high rate of lymph node metastasis and a profound negative impact on patients' quality of life. Despite its severity, no routine screening program currently exists for OSCC. To address the genetic heterogeneity underlying OSCC, we have developed a database of genetic variation in oral squamous cell carcinoma (dbGVOSCC; http://www.sysbio.org.cn/dbGVOSCC/). Methods:OSCC literature (1991-2024) was queried from PubMed and screened manually and via PubTator, following predefined inclusion/exclusion criteria. Entities and relations were extracted from qualifying articles and organized into tables. The database adopted a browser/server architecture using HTML and XAMPP. Front-end was built with HTML and CSS for web display; server-side used Apache for infrastructure, MySQL for data management, and PHP/JavaScript for backend-frontend integration. Bioinformatics included mapping genes to STRING (confidence >0.9), hub gene identification via PPI degree centrality, and GO/KEGG enrichment with clusterProfiler (FDR-corrected). Usability was assessed using SUS and NPS surveys. Results:dbGVOSCC comprises 1,788 somatic genetic variation entries from 400 original studies and 106,079 clinical samples, covering epimutations/methylations (329), SNPs (411), point mutations excluding SNP (258), indels (98), CNVs (348), LOH (28), one locus mutation, plus 333 unspecified mutations. We curated 817 biomarker-linked variations (diagnostic n=71, therapeutic n=175, prognostic n=291; 277 multi-application). PPI analysis highlighted 15 key genes (e.g., TP53, CTNNB1, AKT1, EGFR, PIK3CA). Enrichment implicated proliferation, adhesion/migration, p53/DNA damage response, and PI3K-Akt signaling. User testing showed SUS 88.75 (grade A) and NPS 90. Discussion:dbGVOSCC represents a robust and reliable knowledge base, offering clinicians and researchers an open-source platform for personalized genotype-phenotype association studies and systems genetics research into the mechanisms of OSCC.

ABSTRACT Ulcers, injuries, and various oral surgical treatments frequently cause damage to the oral mucosa. Current oral wound dressings face critical limitations of short protection time due to their weak wet adhesion capability. To address this issue, we developed a Janus bilayer oral wound dressing (P‐N/QCS) with dual functional components. ‌The oral cavity‐facing surface of the P‐N/QCS film demonstrates effective resistance to salivary erosion, while its opposing surface facilitates integration with biological tissues upon absorption of interfacial fluids or blood. This enables immediate adhesion through physical bonding, subsequently reinforced by molecular entanglement and covalent crosslinking. In vitro tests verified that our dressing exhibited significantly superior wet adhesive strength (53.3 ± 3.7 kPa). The protective duration of P‐N/QCS exceeded the commercial product Oral Aid by 521.7% (12 ± 0.5 h vs. 2.3 ± 0.3 h). Additionally, the Janus dressings showed potent hemostatic capability and excellent antibacterial activity. In the model of rat oral ulcer, the adhesive dressings accelerate the healing of the ulcer by suppressing inflammation and promoting epithelialization. In summary, the Janus bilayer oral wound dressing demonstrates promising clinical potential for oral mucosal repair.