Journal of Dental Research最新文献

{"title":"Fighting Age-Associated Bone Loss in Periodontitis with Dietary Interventions.","authors":"A Döding,A Petzold,O Ciaston,M Wichmann-Costaganna,P Schädel,J Symmank,H Noels,C Jacobs,K Becker,O Werz,U Schulze-Späte","doi":"10.1177/00220345251369518","DOIUrl":"https://doi.org/10.1177/00220345251369518","url":null,"abstract":"Aging is a systemic immunomodulatory condition that makes organisms more susceptible to infection-driven periodontitis and associated periodontal tissue loss. Therefore, modulation of the bacterial-induced inflammatory host response could potentially target the pathophysiological systemic and local crosstalk and resulting tissue homeostasis in aged organisms. However, underlying pathways connecting nutritional modulation with periodontal disease pathology and whether an aged organism benefits from specific immunomodulatory nutritional components are not known. Based on its potent immunomodulatory function, we determined whether nutritional interventions with dietary monounsaturated fatty acid (FA) oleic acid (OA [C18:1]), a main component of Mediterranean-style diets, as compared with a Western-style diet component saturated FA palmitic acid (PA [C16:0]) could modify the response to periodontal infection in a murine periodontal Porphyromonas gingivalis-inoculation model comparing old (final age of up to 2 y) and young (21 wk) mice. Local fibroblastic response and circulating regulatory immune-competent lipid mediators (LMs) were determined to provide insights into underlying pathways and how diet and age affect inflammation and resolution of the periodontal infection. The dietary intake of PA enhances periodontal bone destruction in response to P. gingivalis infection in old mice, whereas an OA-enriched diet (ED) has a protective effect. Specifically, PA-ED enhances the inflammatory profile of the periodontal microenvironment and primes gingival fibroblasts, prominent regulators within local tissue homeostasis, toward an inflammatory phenotype. Moreover, systems-wide serological lipidomic analyses of LMs and their respective stimulation of osteoclast differentiation revealed 10-hydroxydocosahexaenoic acid, associated with OA intake, as a protective candidate for age- and nutrition-dependent regulation of osteoclast-driven bone loss. Given the rising prevalence of periodontitis in the aging population, incorporating OA-rich foods could offer promising strategies for addressing the sequelae of aging and promoting periodontal health.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"39 1","pages":"220345251369518"},"PeriodicalIF":7.6,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Caries Control by CAPE Toothpaste: In Vitro, In Vivo, and In Situ Analysis","authors":"Y.F. Wang, S.S. Dong, Y. Chen, Y.H. Zeng, Z.X. Chen, L.L. Zhang","doi":"10.1177/00220345251374959","DOIUrl":"https://doi.org/10.1177/00220345251374959","url":null,"abstract":"Dental caries is closely associated with microbiome dysbiosis. Incorporating antimicrobial agents can enhance the efficacy of fluoride toothpaste. Our previous studies showed that caffeic acid phenethyl ester (CAPE), derived from propolis, effectively inhibited cariogenic bacteria. To formulate a novel CAPE-containing fluoridated toothpaste and establish a multistage evaluation system assessing its caries-controlling efficacy. The CAPE toothpaste’s physicochemical properties were characterized. Its in vitro antimicrobial activity against <jats:italic toggle=\"yes\">Streptococcus mutans</jats:italic> was examined using quantitative suspension and checkerboard microdilution assays. In vivo anticaries efficacy and biosafety were evaluated in a rat caries model ( <jats:italic toggle=\"yes\">n</jats:italic> = 9/group) comparing 5 groups: untreated control (group NC), base toothpaste without CAPE (group B, 600 ppm F <jats:sup>−</jats:sup> ), CAPE–fluoride toothpaste (group C, 0.16 mg/mL CAPE + 600 ppm F <jats:sup>−</jats:sup> ), fluoride control (group F, DARLIE <jats:sup>®</jats:sup> , 600 ppm F <jats:sup>−</jats:sup> ), and propolis nonfluoride control (group P, Red Seal <jats:sup>®</jats:sup> ). Caries severity was scored using the Keyes method. Finally, in situ enamel repair ( <jats:italic toggle=\"yes\">n</jats:italic> = 24 enamel blocks) and plaque microbiome modulation ( <jats:italic toggle=\"yes\">n</jats:italic> = 6 samples) were assessed in a 7-d clinical study (ChiCTR2400089643) with 4 groups (groups NC, C, F, and P). The novel formulation showed stable physicochemical properties. Group C reduced <jats:italic toggle=\"yes\">S. mutans</jats:italic> by 1.5-log10 within 3 min ( <jats:italic toggle=\"yes\">P</jats:italic> = 0.0062 vs NC), and CAPE plus fluoride exhibited additive antibacterial properties (fractional inhibitory concentration index = 0.75). In rats, group C showed the lowest smooth-surface score (21.0 ± 1.7, <jats:italic toggle=\"yes\">P</jats:italic> &lt; 0.005 vs. all) and reduced sulcal lesion severity (slight dentinal lesions: <jats:italic toggle=\"yes\">P</jats:italic> = 0.0181 vs. NC and <jats:italic toggle=\"yes\">P</jats:italic> = 0.0318 vs. F). In situ, group C achieved 27.58% surface microhardness recovery ( <jats:italic toggle=\"yes\">P</jats:italic> &lt; 0.01 vs. all), with significant reductions in mineral loss and lesion depth ( <jats:italic toggle=\"yes\">P</jats:italic> &lt; 0.001 vs. all). Microbiome analysis revealed a preserved microbial diversity, increased <jats:italic toggle=\"yes\">Streptococcus oralis</jats:italic> , and reduced cariogenic populations. The novel CAPE-containing fluoridated toothpaste effectively inhibited the onset and development of caries. Wider-ranging and longer-term clinical investigations are still needed.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"11 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145310748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The AADOCR Position Statement on Community Water Fluoridation","authors":"R. Moffat, M.K.S. Charles-Ayinde, M. Fontana, X. Huang, S. Levy, S.L. Tomar, Y-H. Yu, E. Bell, K. Rwizi, C.H. Fox","doi":"10.1177/00220345251372909","DOIUrl":"https://doi.org/10.1177/00220345251372909","url":null,"abstract":"Community water fluoridation (CWF) is a foundational public health intervention that has significantly reduced the global burden of dental caries across the lifespan. The American Association for Dental, Oral, and Craniofacial Research (AADOCR) reaffirms its strong support for CWF as a safe, evidence-based, and cost-saving method of delivering fluoride equitably to large populations. This updated position statement synthesizes nearly 8 decades of scientific literature, national surveillance data, and expert consensus to underscore the caries-preventive benefits of CWF and the role of fluoridation in reducing oral health disparities. AADOCR recommends the continued fluoridation of public water supplies at the optimal level of 0.7 mg/L and calls for sustained efforts in monitoring safety, improving public communication, and advancing research into fluoride’s impact on oral and systemic health.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"38 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Snapshot of the Seconds-Pellicle: Ultrastructure and Proteomic Changes.","authors":"S Trautmann,S Thangamurugan,C Fecher-Trost,J Dudek,V Flockerzi,V Helms,M Hannig","doi":"10.1177/00220345251379764","DOIUrl":"https://doi.org/10.1177/00220345251379764","url":null,"abstract":"The dental pellicle is a continuously forming layer present at the interface between oral surfaces and saliva. It protects the dental surfaces by shielding against chemical and mechanical damages. The pellicle represents the basis for further biofilm development, and its formation starts after oral hygiene through the adsorption of mostly salivary proteins to all exposed oral surfaces. In spite of its important physiologic role, its formation process and composition are not yet revealed in all details. The objective of the current study was 1) to visualize and elucidate the individual proteomic composition of the very early (only a few seconds) formed in situ pellicle, named seconds-pellicle, and 2) to analyze changes in its ultrastructure and proteomic composition over time. Transmission electron microscopic analyses demonstrated the seconds-pellicle to consist of an already continuous electron-dense layer without a detectable increase in thickness within the first minutes of formation. Proteomic analyses showed it to consist of up to 841 proteins on an individual level, without elevating protein content or diversity over the first minutes. Analyses of several pellicle formation times enabled the detection of changes over time and the first direct verification of protein desorptions occurring during pellicle formation. Comparisons between the salivary and pellicle proteomes at the different formation times revealed insights in the amount of substance of single pellicle proteins over time. The present study provides first evidence that the pellicle forms instantaneously and dynamically on solid surfaces in the oral cavity. Furthermore, the data suggest these first proteins to be replaced by proteins adsorbing with higher selectivity to stabilize the pellicle within the first minutes of its formation. These insights represent the basis for selective modifications of the pellicle layer to control the originating biofilm and develop preventive strategies for oral biofilm management.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"342 1","pages":"220345251379764"},"PeriodicalIF":7.6,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifunctional Primer for Dentin Bonding via Biomimetic Mineralization","authors":"S.H. Yang, Z.L. Tian, H.M. Wang, D. Sun, S.W. Qiao, Z.S. Shi, X. He, S. Zhu","doi":"10.1177/00220345251381633","DOIUrl":"https://doi.org/10.1177/00220345251381633","url":null,"abstract":"Enhancing the durability of dentin bonding remains a significant challenge in dental restoration. This study introduces an innovative approach using aldehyde-grafted polyaspartate (PACA) to achieve spatiotemporal regulation of biomimetic mineralization through collagen cross-linking. The collagen cross-linking capability of PACA was confirmed by sodium dodecyl sulfate–polyacrylamide gel electrophoresis analysis. Its ability to induce intrafibrillar mineralization of collagen fibrils was investigated using a rat tail collagen model through dynamic light scattering, zeta potential measurements, and transmission electron microscopy. In addition, the remineralization efficacy of PACA on demineralized dentin collagen was evaluated using scanning electron microscopy, energy dispersive X-ray spectroscopy, and atomic force microscopy. These analyses revealed that PACA facilitates intrafibrillar mineralization by creating an amorphous calcium phosphate–rich microenvironment in the cross-linked region. Subsequently, the mineralization encapsulates the covalently cross-linked polymer and collagen fibrils within a mineralized matrix, forming an organized crystalline structure. Furthermore, PACA was used as a single-component primer in a dentin bonding model, and its impact on bonding durability was assessed through micro-tensile bond strength testing, nanoleakage analysis, and in situ zymography. These assessments demonstrate that PACA could simultaneously achieve collagen cross-linking, matrix metalloproteinase inhibition, and enhanced adhesive penetration while facilitating temporally regulated mineralization. Due to this multifunctionality, the PACA primer significantly improves micro-tensile bond strength and exhibits favorable durability after the aging experiment. This innovative approach provides a promising solution to the durability limitations of conventional adhesive systems.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"63 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Apically Localized Endogenous Dental Pulp Stem Cells.","authors":"S Yoshida,E O Maruyama,W Hsu,G T-J Huang,T Maruyama","doi":"10.1177/00220345251378094","DOIUrl":"https://doi.org/10.1177/00220345251378094","url":null,"abstract":"Dental pulp is crucial for maintaining tooth vitality and function. Vital pulp provides defense mechanisms, sensory function, and tooth structural integrity. The presence of dental pulp stem cells (DPSCs) plays a role in the regeneration of damaged pulp and dentin. In immature teeth, the apical papilla at the apex harbors stem cells that are involved in root formation and maturation. Although stem cells isolated from the pulp and apical papilla have shown regenerative capacities, the in situ process of their involvement in pulp and dentin regeneration in response to injury is still unclear. Here, using single-cell transcriptomics and lineage tracing techniques, we identified the presence of endogenous Axin2+ DPSCs localized at the apex of mouse molars. The single-cell profiling identified 6 subpopulations of molar pulp tissue, including odontoblasts, pulp cells, and DPSCs. Lineage tracing analysis revealed that Axin2+ DPSCs gradually expand at the root apex and differentiate into pulp cells within the canal, contributing to pulp tissue formation in the pulp chamber and eventually maturing into odontoblasts over a period of at least 9 months. Upon pulp exposure or injury, the DPSCs rapidly proliferate and facilitate pulp healing and reparative dentin formation. Furthermore, the regenerative potential of the isolated DPSCs was demonstrated through their transplantation into the kidney capsule, leading to the successful formation of ectopic pulp tissue and reparative dentin. Identifying novel DPSCs at the apex provides new insights into pulp biology and establishes a foundation for regenerative endodontic therapies, leading to the deciphering of underlying mechanisms and development of new therapeutic strategies.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"39 1","pages":"220345251378094"},"PeriodicalIF":7.6,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Periodontal Health and Outcome of Atherosclerotic Disease in the Hamburg City Health Study","authors":"B. Bay, K. Borof, B. Cheng, B. Lieske, L. Tilemann, L. Wees, B.-C. Zyriax, C.-A. Behrendt, G. Thomalla, S. Blankenberg, T. Beikler, R. Twerenbold, F.J. Brunner, G. Aarabi","doi":"10.1177/00220345251365596","DOIUrl":"https://doi.org/10.1177/00220345251365596","url":null,"abstract":"Periodontitis (PD) as chronic inflammatory disease has been linked with the development of atherosclerotic cardiovascular disease (ASCVD). However, there is a lack of data with regard to the association of PD across the extent of ASCVD and clinical outcomes, which we sought to investigate. Randomly recruited participants from the Hamburg City Health Study were included. The cohort was grouped according to severity of ASCVD at baseline: no ASCVD, monovascular disease (MonoVD), and polyvascular disease (PolyVD). PD was assessed categorically by degree of severity and continuously by clinical attachment loss. Logistic regression models were implemented to investigate the association of PD with prevalent ASCVD subtypes. Kaplan-Meier curves and Cox regression analyses were computed to investigate the associations of clinical attachment loss with major adverse cardiovascular events (composite of all-cause death, myocardial infarction, ischemic stroke, any unplanned coronary revascularization, and new diagnosis of cerebrovascular disease or peripheral arterial disease) across the extent of ASCVD. Across the 6,209 individuals included ( <jats:italic toggle=\"yes\">n</jats:italic> = 3,049, no ASCVD; <jats:italic toggle=\"yes\">n</jats:italic> = 2,283, MonoVD; <jats:italic toggle=\"yes\">n</jats:italic> = 877, PolyVD), participants with PolyVD had the highest rates of severe PD. On binary logistic regression analysis, severe PD was independently associated with MonoVD (odds ratio, 1.32; 95% CI, 1.09 to 1.61; <jats:italic toggle=\"yes\">P</jats:italic> = 0.005) and PolyVD (odds ratio, 1.57; 95% CI, 1.16 to 2.13; <jats:italic toggle=\"yes\">P</jats:italic> = 0.004). During a median follow-up of 5.5 y (95% CI, 5.3 to 5.6), a trend toward higher major adverse cardiovascular event rates was observed in individuals with ASCVD and the highest clinical attachment loss tertile. However, no independent association of mean clinical attachment loss with adverse events was noted. PD is highly prevalent in patients with more extensive ASCVD, and severe PD is associated with MonoVD and PolyVD. However, no association of PD with major adverse cardiovascular events was noted. These data suggest that PD may be associated with cardiovascular risk in the population.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"100 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Milk EVs Promote Apical Periodontitis Bone Repair via Osteoblast Targeting.","authors":"S-X Wu,Q-Y Song,H Bai,Y-R Shang,Z-R Yan,M Xia,L-N Wang,M Dong,W-D Niu","doi":"10.1177/00220345251368767","DOIUrl":"https://doi.org/10.1177/00220345251368767","url":null,"abstract":"Chronic apical periodontitis (CAP), an inflammatory disease of periapical tissues, leads to alveolar bone destruction. Current therapies lack osteoblast-targeting specificity and fail to effectively promote bone repair. Extracellular vesicles (EVs), particularly milk-derived EVs (MEVs), show potential for bone regeneration and have anti-inflammatory effects. We investigated the therapeutic potential of engineered MEVs modified with the osteoblast-targeting peptide DSPE-PEG-Mal-Cys-SDSSD (DPS) in CAP. DPS-MEVs enhanced osteogenic capacity and exhibited greater osteoblast targeting compared with unmodified MEVs through oxidative phosphorylation (OXPHOS) activation, driven by Kruppel-like factor 4 (KLF4)-mediated upregulation of NADH dehydrogenase 1 alpha subcomplex 4 (Ndufa4) in vivo and in vitro. We also transplanted DPS-MEVs into a CAP model of dogs through apical microsurgery and found that DPS-MEVs enhanced bone repair and reduced inflammation by promoting polarization of M2 macrophages. These findings highlighted the potential of engineered DPS-MEVs as a dual-functional therapy for CAP, combining immunomodulation and tissue repair to advance precision treatment for inflammatory bone diseases.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"36 1","pages":"220345251368767"},"PeriodicalIF":7.6,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systems Sciences in Dentistry: A Critical Review.","authors":"N Dritsch,C Bedos,J-N Vergnes","doi":"10.1177/00220345251381690","DOIUrl":"https://doi.org/10.1177/00220345251381690","url":null,"abstract":"Despite substantial clinical progress under the biomedical paradigm, global oral disease burdens remain high, highlighting the need for integrated and context-sensitive models. This critical review examines how systems sciences can contribute to redefining dentistry's role within contemporary health systems. While systems thinking dates back nearly a century, its application to dental research and policy has expanded significantly in recent years. The objectives of this review are to assess the relevance of systems sciences in addressing current health challenges involving dentistry and to analyze how these approaches have informed dental science and practice to date. Based on a thematic analysis of the literature, the review identifies emerging conceptual frameworks, practical applications across multiple dental domains, and areas requiring further exploration. The review distinguishes between predictive approaches, such as simulation and modeling, and relational paradigms rooted in interdependence, context, and goal-oriented dynamics. It documents recent applications of these frameworks in public health, clinical planning, education, environmental strategy, and patient care. Three widely shared assumptions are finally revisited through systems sciences perspectives: the framing of \"oral health\" as an isolated individual outcome, the dichotomy between \"prevention\" and \"treatment,\" and the notion that oral diseases are largely \"preventable.\" While such assumptions may serve communication or policy purposes, they can obscure structural determinants and limit systemic integration of actions against the burden of oral diseases. Systems sciences provide methodological and conceptual tools to reposition dentistry as a contributor to broader health goals: reducing population-level treatment needs, improving access, and addressing upstream determinants of health. Rather than promoting technical growth alone, dental research should place greater emphasis on systemic approaches to ensure that available resources effectively serve population needs. As a scientific framework, systems sciences are not only compatible with these aims but are also essential to achieving them in a coherent, evidence-based, and socially relevant manner.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"13 1","pages":"220345251381690"},"PeriodicalIF":7.6,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage-Targeted Self-Assembled Nanosystem for Periodontitis Treatment.","authors":"Y Jin,J Du,Z Wang,S Ge,B Ma","doi":"10.1177/00220345251355267","DOIUrl":"https://doi.org/10.1177/00220345251355267","url":null,"abstract":"Periodontitis is a chronic inflammatory disease triggered by pathogenic bacteria, with intracellular bacteria and biofilm contributing to persistent periodontal inflammation. In this context, macrophages can be portrayed as a privileged niche for long-term bacterial colonization, leading to further disruption of the immune microenvironment rather than its modulation. Here, a macrophage-targeted metal-organic/polyphenol self-assembly nano drug delivery system was designed for on-site drug delivery and microenvironment restoration. The nanoparticles were synthesized by hyaluronic acid functionalization on the surface of curcumin (Cur)-loaded zeolitic imidazolate framework-8 (denoted as ZCH NPs). ZCH NPs selectively targeted macrophages through CD44 receptor-mediated endocytosis. Following cellular uptake, the nanoparticles underwent pH-responsive degradation in the acidic lysosomal environment (~pH5), releasing zinc ions and Cur. The dual release exerted optimal therapeutic effects, including anti-inflammatory and immunomodulatory activities, through the PPAR/Notch signaling pathways. Furthermore, ZCH NPs restored the osteogenic potential of stem cells in an inflammatory environment by rebalancing the immune microenvironment. ZCH NPs also eliminated extracellular and intracellular bacteria and inhibited biofilm formation. Ultimately, ZCH NPs alleviated inflammatory bone resorption in rat experimental periodontitis, with the reduction of cementoenamel junction-alveolar bone crest from ~568 to ~250 µm. Therefore, periodontal tissue regeneration was promoted by eradicating pathogenic bacteria, modulating immune response, and facilitating osteogenic differentiation. Collectively, through on-site and responsive drug delivery, ZCH NPs exhibited superior efficacy in treating periodontitis, providing a promising strategy for addressing infection-related chronic inflammatory diseases.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"11 1","pages":"220345251355267"},"PeriodicalIF":7.6,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}