Journal of Dental Research

Schwendicke, F.; Sidhu, S.K.; Ferracane, J.L.; Tichy, A.; Jakubovics, N.S.

doi: 10.1177/00220345251356408pmid: 41091144

Generative artificial intelligence (AI) has the capability to generate new content—including text, code, imagery, video, and speech—based on human prompts and is entering dental and oral research. By retrieving, analyzing, summarizing, and contextualizing vast datasets, generative AI offers substantial potential to enhance scientific workflows. It can improve documentation, communication, and reproducibility while saving time and accelerating discovery. However, its integration into research brings significant ethical, societal, and scientific challenges. Concerns include embedded data biases, automation bias, overreliance, and error propagation, all requiring critical human oversight. Furthermore, generative AI raises complex issues around plagiarism, fraud, attribution, and reproducibility, compounded by the potential for AI “hallucinations” or fabricated content. Addressing these concerns demands transparency, robust verification processes, ethical compliance, and clear documentation distinguishing synthetic from real-world data. Several scientific and regulatory bodies have published guidelines to support responsible AI use. Recommendations relevant to scientists in dental, oral, and craniofacial research include transparent disclosure of AI tools and methods, thorough verification of AI outputs, ethical oversight, and active monitoring. Scientists are urged to work collaboratively with stakeholders to enforce these principles and engage the public in the evolving discourse. The risk of misuse, particularly through fraudulent AI-generated publications, is growing. Paper mills exploiting generative AI can produce fabricated or manipulated articles, which may mislead the scientific community and distort evidence bases. Coordinated action, involving journals, institutions, and ethics bodies, is essential to combat these threats. As generative AI continues to evolve, adaptive and harmonized guidelines will be necessary to safeguard scientific integrity. Researchers, reviewers, and editors must play a proactive role in ensuring that AI serves to advance—not undermine—the quality and trustworthiness of dental and oral science.

Wang, S.; Song, F.; Liang, S.; Huang, C.; Yang, H.

doi: 10.1177/00220345251361795pmid: 40888153

Mineralized collagen fibrils constitute the fundamental structural units within collagenous mineralized tissues (CMTs), particularly in bone and dentin, where they play a critical role in maintaining mechanical resilience and structural integrity. The mechanical microenvironment of CMTs is dynamically shaped by diverse physiologic loads from muscle contraction, body support, vascular system pressure, orthodontic movement, and mastication. While many reviews have covered cellular responses to mechanical stimuli, they often focus on cell differentiation at the generalized cellular level and lack a microscopic and dynamic perspective on mineralized collagen formation. There is an urgent need to review the behavior of collagen fibrils as primary effectors in response to mechanical stimuli. On the basis of compartmental changes and structural evolution, herein we analyze the effects of mechanical stimuli on mineralized collagen formation through 3 distinct stages: 1) intracellular collagen synthesis, where mechanical stimuli can regulate intracellular collagen synthesis at the gene level; 2) extracellular collagen assembly, where appropriate mechanical stimuli can induce orderly collagen fibril arrangement; and 3) intrafibrillar collagen mineralization, where mechanical stimuli can facilitate effective intrafibrillar mineralization. In this review, we trace the mechanobiological journey of mineralized collagen, showcase the latest research advancements in this field, and propose future perspectives. This review may aid in developing novel therapeutic strategies to improve CMT homeostasis and draw attention to the application of biomimetic mechanical microenvironments in tissue engineering.

Tuwatnawanit, T.; Anthwal, N.; Tucker, A.S.

doi: 10.1177/00220345251363561pmid: 41103044

The temporomandibular joint (TMJ) plays a critical role in the daily activities of mastication and communication, with disorders of the TMJ significantly impairing quality of life. Temporomandibular disorders (TMDs) are highly prevalent, presenting a pressing need for regenerative therapies. The TMJ’s key components—condyle, TMJ disc, and glenoid fossa—are crucial for proper function; however, the limited self-repair capability of these tissues makes managing TMJ pathology particularly challenging. Emerging research in animal models has emphasized the importance of fibrocartilage stem/progenitor cells (FCSCs) located in and around the superficial layers of the condyle. Lineage tracing of condylar FCSCs in vivo has identified subpopulations with different contributions to growth and homeostasis, providing potential targets for regenerative therapies. In addition to the FCSCs, niche-supporting cells have been recently identified in the superficial layers of the condyle, further highlighting the complex cellular environment of the TMJ. Several signaling pathways, including Wnt, Hedgehog, and Notch, play pivotal roles in establishing cell fate in the developing and growing TMJ and have been additionally implicated in both the control of FCSC populations and progression of TMDs. Recent research has used this understanding of the signaling pathways involved in the creation of the joint to stimulate the endogenous stem cells/FCSCs of the adult in vivo, leading to enhancement of regenerative capacity in mouse, rat, rabbit, and porcine injury and disease models. Manipulation of signaling pathways has been combined with advanced bioengineering techniques, providing scaffolds to allow controlled dispersal of activators and inhibitors. Such advances in understanding the triggers and molecular mechanisms that control TMJ FCSCs, combined with improved targeting of specific signaling pathways, have opened new avenues for regenerative therapies. These insights have begun to be leveraged in the development of novel hydrogel-based injectable regenerative therapeutic approaches to not only alleviate symptoms but also promote true regeneration of TMJ structures.

Yan, I.G.; Zheng, F.M.; Sun, I.G.; Lo, E.C.M.; Duangthip, D.; Chu, C.H.

doi: 10.1177/00220345251345801pmid: 40583169

Clinicians have recommended, with no scientific evidence, increasing the application times of 38% silver diamine fluoride (SDF) to foster caries arrest. The current study determined the rate of carious lesion activity in response to topical 38% SDF with increasing treatment application time. A 6-mo, stratified-randomized, double-blind, active-controlled, parallel-group trial compared 9 treatment arms. The primary outcome was carious lesion activity at the tooth-surface level 6 mo after initial treatment. Participants included 665 children aged 3 to 4 y with 2,106 carious teeth (234 teeth/group) with 3,024 active carious tooth surfaces. The carious teeth were block randomized into 9 groups with SDF application times of 3, 5, 10, 15, 30, 45, 60, 120, and 180 s. The dose (SDF application time) and response (proportion of active carious tooth surfaces becoming arrested) were modeled using multiple dose-response models. At the 6-mo examination, 642 children with 2,038 SDF-treated carious teeth and 2,939 SDF-treated carious tooth surfaces were evaluated. The estimated proportion of inactive (arrested) lesions (%) increased over time from 75% at 4 s, to 80% at 16 s, and 84% at 60 s. Among the multiple dose-response models, the Emax model provided the best fit. The estimated rate of the proportion of arrested lesions (%s−1) reduced over time from 0.1%s−1 at 30 s to 0.05%s−1 at 43 s. An estimated 16-s application time was required to arrest 80% of caries lesions. The proportion of arrested lesions was associated with lesion-surface type (single/multiple) and tooth location (anterior/posterior). A 16-s application time was estimated to arrest 88% of single tooth-surface lesions in anterior teeth, compared with 66% of multiple tooth-surface lesions in posterior teeth. In conclusion, the trial found an increase in the proportion of arrested lesions with increasing SDF application time, although the rate of the proportion of arrested lesions decreased over application time. (ClinicalTrials.gov NCT04655430)

Chisini, L.A.; Costa, F.S.; Correa, M.B.; Peres, M.A.; Peres, K.G.; Matijasevich, A.; Santos, I.S.; Barros, A.J.D.; Demarco, F.F.

doi: 10.1177/00220345251337392pmid: 40569821

This study aims to explore the pathways through which socioeconomic position (SEP) at birth influences oral health self-perception in adolescence. A representative sample (N = 1,120) of all births from the 2004 Pelotas cohort was prospectively investigated. Interviews and clinical examinations were performed at 5 and 12 y. Gingivitis was assessed at 12 y. Dental caries (dmf-t/DMF-T), malocclusion, and the use of dental services were assessed at 5 and 12 y. SEP at birth (latent variable) was the main exposure. The outcome was a negative oral health self-perception at 18 y. Missing data were imputed using multivariate imputation. Structural equation modeling (SEM) was used to estimate the direct, indirect, and total effects from SEP to outcome. A negative perception of oral health self-perception was reported by 21.5% of the adolescents. SEP at birth influences, directly and indirectly, oral health self-perception at 18 y old. A direct effect (standard coefficient [SC] = −0.28, P < 0.001) and an indirect effect (SC = −0.04, P < 0.001) of SEP were observed on oral health self-perception. Dental caries at 12 y was the main mediator pathway between SEP and oral health self-perception with significant results (SC = −0.03, P < 0.001). The pathways through occlusal status at 12 y (P = 0.989) and gingivitis (P = 0.238) were not statistically significant. The total effect of SEP on negative self-perception of oral health was SC = −0.32 (P < 0.001). Thus, SEP at birth directly and indirectly influenced oral health self-perception at the age 18 y. SEM shows that the main pathway was direct. The main indirect effect was thought to be dental caries at 12 y.

Alkhars, N.; Manning, S.; Al Jallad, N.; Zeng, Y.; Wu, T.T.; Fogarty, C.; Mendoza, M.; van Wijngaarden, E.; Kopycka-Kedzierawski, D.T.; Billings, R.; Fiscella, K.; Koo, H.; Xiao, J.

doi: 10.1177/00220345251340040

Binvignat, P.; Valette, S.; Hara, A. T.; Lahoud, P.; Jacobs, R.; Chaurasia, A.; Ducret, M.; Richert, R.

doi: 10.1177/00220345251344548pmid: 40598953

More than 1 billion individuals worldwide have experienced dental trauma, particularly children aged 7 to 12 y, predominantly affecting the anterior teeth, which has a significant impact on oral health and esthetics. Rapid emergency restorations using composite resin are followed by medium-term lab-fabricated mock-ups. Recent advancements in artificial intelligence (AI) assist dental restorations, and the objective of this study was to compare the performances of different AI approaches for the learning and reconstruction of central incisors. The study was approved by ethical committees and followed AI in dentistry recommendations. STL files of mature permanent maxillary incisors without severe wear were collected from 3 universities. Principal component analysis (PCA) and Deep Learning of Signed Distance Functions (DeepSDF) models were trained using these files. The learning of PCA and DeepSDF approaches were 3-fold cross-validated, and their performances were assessed using the following metrics to measure the reconstruction accuracy: the difference of surfaces, volumes, lengths, average Euclidian distance, Hausdorff distance, and crown–root angulations. Explainability was assessed using feature contribution analysis for PCA and Stochastic Neighbor Embedding (t-SNE) for DeepSDF. DeepSDF showed significantly better precision in surface, volume, and Hausdorff distance metrics compared with PCA. For reconstructions, the lower size of the latent code of the DeepSDF model demonstrated lower performances compared with higher sizes. In addition, DeepSDF raised concerns about explainability. This study demonstrates the potential of PCA and DeepSDF approaches, particularly DeepSDF, for the learning and reconstruction of the anatomy of upper central incisors. To foster trust and acceptance, future research should, however, focus on improving the explainability of DeepSDF models and considering a broader range of factors that influence smile design. These high performances suggest potential clinical applications, such as assisting practitioners in future smile designs and oral rehabilitation using AI approaches.

Bao, K.; Oscarsson, J.; Gehring, P.; Grossmann, J.; Belibasakis, G.N.; Bostanci, N.

doi: 10.1177/00220345251337745pmid: 40574274

Aggregatibacter aphrophilus is the only known oral bacterium with a functional type VI secretion system (T6SS) that acts against Aggregatibacter actinomycetemcomitans. Bacteria use the T6SS to deliver toxic effectors into bacterial or eukaryotic cells during interbacterial competition or host colonization. To date, the T6SS of A. aphrophilus has not been demonstrated to participate in antieukaryotic activity, nor have the cytotoxic effectors involved been identified. Here, we identified 2 T6SS effectors in A. aphrophilus, a glycosyl hydrolase (Glh) and a phospholipase D (Tle5), which, upon inactivation of their respective genes, together resulted in abolished T6SS activity against A. actinomycetemcomitans in multispecies biofilms. Next, we probed the role of the 2 T6SS effectors in host–cell interactions using gingival keratinocytes. Interestingly, although neither of the effectors appeared to contribute to the acute inflammatory response directly, the co-presence of both species reduced the inflammatory effect, likely due to the T6SS-dependent elimination of A. actinomycetemcomitans, hence decreasing the bacterial abundance. This reduction was not observed using A. aphrophilus mutants lacking the effectors or the T6SS “tube” core protein, hemolysin co-regulated protein (Hcp). Here, we show that the T6SS effectors in A. aphrophilus have distinct functions in eukaryotic versus bacterial cell interactions. Hence, these T6SS effectors may represent novel mechanisms of interaction between bacteria and the oral–mucosal barrier, offering potential therapeutic targets for managing periodontal pathogens.

Nie, L.; Sun, Y.; Dong, H.; You, M.; Cui, A.; Yue, Z.; Zhao, P.; Lv, Q.; Ji, N.; Wang, H.; Xu, X.; Leung, W.K.; Wang, J.; Wang, Q.

doi: 10.1177/00220345251340632pmid:

Feng, C.; Dou, X.; Li, S.-R.; Xu, X.; Dang, Z.; Jiang, Z.; Jiang, E.; Shang, Z.

doi: 10.1177/00220345251340892pmid: 40574412

The clinical classification of ameloblastoma (AM) plays a decisive role in the selection of treatment options, but the difference of single-cell landscape among clinical classifications is still unclear. At the same time, there is an urgent need to understand the key cell subtypes that determine the clinical subtypes. We characterized the single-cell transcriptional profiles of clinical subtypes of AM. We also characterized a pseudotime transition trajectory from immunoactive epithelial cells to vascular-associated fibroblasts, identifying key transcription factors involved in this process. Notably, we observed significant heterogeneity between M1 and M2 macrophages among the clinical subtypes of AM. Furthermore, our analysis revealed that metabolic disorder in AM was primarily driven by the metabolic disturbances in M1 and M2 macrophages. At the cellular communication level, we highlighted the role of M2 macrophages in mediating cell interactions, focusing on the RANKL/RANK pathway associated with osteoclast activity. Finally, we attempted to establish a unicystic AM–derived epithelial cell line and utilized it to construct an AM-like organoid model; we found that M2 macrophages competed with AM for L-cysteine to achieve cystic changes in the solid lesion. Our exploration of pathogenesis underlying various clinical types of AM advances our knowledge of AM heterogeneity, offering promising targets for novel therapeutic strategies.