Raman confocal microscopy atlas of human tooth.

To investigate the vascularization capacity of a decellularized dental pulp matrix (DDP) of bovine origin seeded with human dental pulp stem cells (hDPSCs) in vitro and to present preliminary in vivo findings. Bovine dental pulps were decellularized and then analysed using histological staining and DNA quantification. The resultant DDPs were characterized using immunohistochemical staining for the retention of vascular endothelial growth factor A (VEGF-A) and fibroblast growth factor 2 (FGF-2). Furthermore, DDPs were recellularized with hDPSCs and analysed histologically. The expression of markers involved in angiogenesis by hDPSCs colonizing the DDPs was assessed in vitro. A preliminary in vivo study was then conducted in which hDPSCs-seeded and unseeded DDPs were inserted in debrided human premolars root slices and implanted subcutaneously in immunodeficient mice. Samples were retrieved after 30days and analysed using histological and immunohistochemical staining. The independent samples t-test, analysis of variance and a Kruskal-Wallis test were used to analyse the quantitative data statistically depending on the group numbers and normality of data distribution. The difference between the groups was considered significant when the P-value was less than 0.05. Acellular dental pulp matrices were generated following bovine dental pulp decellularization. Evaluation of the developed DDPs revealed a significant DNA reduction (P<0.0001) with preservation of the native histoarchitecture and vasculature and retention of VEGF-A and FGF-2. Upon recellularization of the DDPs with hDPSCs, the in vitro analyses revealed cell engraftment with progressive repopulation of DDPs' matrices and vasculature and with enhanced expression of markers involved in angiogenesis. In vivo implantation of root slices with hDPSCs-seeded DDPs revealed apparent vascularization enhancement as compared to the unseeded DDP group (P<0.0001). The developed decellularized dental pulp matrix had pro-angiogenic properties characterized by the retention of native vasculature and angiogenic growth factors. Seeding of hDPSCs into the DDP led to progressive repopulation of the vasculature, enhanced expression of markers involved in angiogenesis in hDPSCs and improved in vivo vascularization capacity. The se suggest that a combination of DDP and hDPSCs have the potential to provide a promising vascularization promoting strategy for dental pulp regeneration.

A Customized Self-Assembling Peptide Hydrogel for Dental Pulp Tissue Engineering

Ontology and the Future of Dental Research Informatics

Quantitative detection on metabolites of Haematococcus pluvialis by terahertz spectroscopy

In dental practice, Regenerative Endodontic Treatment (RET) is applied as an alternative to classical endodontic treatments of immature necrotic teeth. This procedure, also known as dental pulp revitalization, relies on the formation of a blood clot inside the root canal leading to the formation of a reparative vascularized tissue similar to dental pulp, which would provide vitality to the affected tooth. Despite the benefit of this technique, it lacks reproducibility due to the fast degradation and poor mechanical properties of blood clots. This work presents a method for constructing a fibrinogen-blood hydrogel that mimics the viscoelastic properties of human dental pulp while preserving the biological properties of blood for application in RET. By varying the blood and fibrinogen concentrations, gels with different biomechanical and biological properties were obtained. Rheology and atomic force microscopy (AFM) were combined to study the viscoelastic properties. AFM was used to evaluate the elasticity of human dental pulp. The degradation and swelling rates were assessed by measuring weight changes. The biomimetic properties of the gels were demonstrated by studying the cell survival and proliferation of dental pulp cells (DPCs) for 14 days. The formation of an extracellular matrix (ECM) was assessed by multiphoton microscopy (MPM). The angiogenic potential was evaluated by an ex vivo aortic ring assay, in which the endothelial cells were observed by histological staining after migration. The results show that the Fbg-blood gel prepared with 9 mg ml-1 fibrinogen and 50% blood of the Fbg solution volume has similar elasticity to human dental pulp and adequate degradation and swelling rates. It also allows cell survival and ECM secretion and enhances endothelial cell migration and formation of neovessel-like structures.

The dental pulp is a highly vascularized and innervated connective tissue located at the central part of the tooth and composed of a diverse array of cell types, including fibroblasts, multipotent mesenchymal stem cell, odontoblasts, and immune cells. Traumatic injuries and carious lesions can lead to dental pulp pathologies that often require replacement of damaged tissue with inert materials. Despite significant progress in recent years, cell-based dental pulp regenerative therapies remain distant from clinical applications. The lack of platforms capable of accurately modeling the human dental pulp in all its complexity hampers the development of novel therapeutic strategies. In response, numerous efforts have been focused on the development of innovative microfluidic systems designed to emulate human dental pulp physiology. These "dental pulp-on-chip" platforms enable the recreation of structural and functional complexity in an in vivo-like environment, opening new horizons for patient-specific endodontic therapies and providing valuable tools for targeted drug testing. This review focuses on state-of-the-art microfluidic devices designed to emulate the dental pulp and their specific applications in dental materials testing, drug evaluation, and pulp regeneration. By integrating multiple cell types, biomaterials, and bioactive cues within dynamic microenvironments, "dental pulp-on-chip" devices overcome the constraints of traditional in vitro cultures and animal models and enable the assessment of treatment-induced systemic effects, an aspect often overlooked in dental research. Continued advancements in "dental pulp-on-chip" technology will be pivotal for bridging preclinical research and clinical practice in dental medicine.

Training the Future: Protecting the Scope and Diversity of Oral and Maxillofacial Surgery

Characterization of lipid in mature enamel using confocal laser scanning microscopy

Little is known about the aging per se of the oral mucosa, the salivary glands, the dental pulp or the periodontium. Even less is known about the relationship of the aging immune system to periodontal disease or to oral cancer. The interrelationship of aging body systems to oral biology is dentistry's challenge for the future. This conference paper is designed to stimulate some thinking, planning, and activity in the dental research community.

Hunter-Schreger Bands (HSBs) are an optical phenomenon visualised when a cut or fractured enamel surface is viewed under reflected light. These bands demonstrate the synchronous decussation of individual or groups of enamel prisms. While the role of HSB patterns has been investigated in comparative anatomical studies, until recently there has been little consideration of HSB patterns in human teeth. The aim of this paper is to consider the significance of HSB patterns in the human dentition and in relation to clinical dentistry. It is concluded that within the human dentition, HSB patterns have evolved to optimise resistance to attrition, abrasion and tooth fracture. It appears that certain aspects of HSB packing densities and distributions have beneficial roles in enamel bonding. Hunter-Schreger Band patterns seem to passively facilitate conditions such as abfraction and cracked tooth syndrome.

Interest in addressing the unmet oral health needs of the citizens of the world has manifested itself, lately, in noteworthy expressions of commitment. Oral health is integrated with general health and support for community programmes offering 'essential oral health' within primary health care (PHC) is increasing. The WHO Global Goals for Oral Health 2020 has assumed a more directed public health orientation, and the Global Oral Health Programme has its focus on modifiable oral risk behaviours. Last, but not the least, opportunities are being created, under the 'stewardship' of the World Health Organization (WHO), for the expansion of oral disease prevention and health promotion knowledge and practices in communities. A review of the literature on community-oriented oral health primary care reveals one dominant and disease-oriented practice model with dental practitioners being the principal and exclusive actors. One alternative to this biomedical model of care that may be better suited to translate health promotion principles into action at community levels is the practice that involves hygienists serving as primary oral health care providers. The WHO 'stewardship' should include the support of dental hygiene practice within PHC, many legislative restrictions and regulatory barriers would be relaxed, thus enabling dental hygienists to respond to the WHO's call for community-based demonstration projects. With their focus on preventive oral care, hygienists are 'best poised' to help accelerate the integration of oral health with primary care, particularly in the light of the compelling evidence confirming the cost-effectiveness of the care delivered by intermediate providers.

“Oral health matters” was the clear and emphatic message on the front cover of The Lancet on July 20, 2019. In this single issue of The Lancet, in addition to the front cover, oral health was the focus of an editorial (The Lancet 2019), an Oral Health Series comprising 2 major papers (Peres et al. 2019; Watt et al. 2019), 2 associated commentaries (Beaglehole and Beaglehole 2019; Kearns and Bero 2019), a perspective piece on the historical origins of modern dentistry (Barnett 2019), and a profile of a dental public health researcher (Davies 2019). Never before in the 196-year history of The Lancet—one of the most prestigious medical journals in the world—has oral health been given such a high profile. This is, without doubt, a watershed moment for global oral health. It is also, however, a profoundly important opportunity for the oral and dental research community. This commentary highlights the key messages from The Lancet Oral Health Series and considers the implications for the oral and dental research agenda globally.

This study investigated the effects of lactate-induced lactylation in the inflammatory microenvironment of pulpitis and further explored the mechanism. Lactate levels in pulpitis samples were quantified using a high-sensitivity assay. Histological, immunohistochemical, and immunofluorescence staining were conducted to evaluate lactylation, macrophage marker, pro-inflammatory, and anti-inflammatory markers. A time-course murine experimental pulpitis model (0-72 h) was established to characterise lactylation dynamics during inflammatory progression in pulpitis. An invitro inflammatory dental pulp microenvironment model of THP-1 macrophages cocultured with LPS-pretreated dental pulp cells derived conditioned media (iCM) was developed to investigate lactate production and macrophage phenotypes. Transcriptomic profiling identified differentially expressed genes, with gene set enrichment analysis (GSEA) employed to assess the functions of differentially expressed genes. Transmission electron microscopy, quantitative real-time PCR (qRT-PCR), concurrent oxygen consumption rate (OCR), and extracellular acidification rate (ECAR) were measured to evaluate the mitochondrial activity of iCM-pretreated macrophages. Mouse experimental pulpitis models treated with iCM were conducted to evaluate anti-inflammation and pro-healing properties by histological, immunohistochemical, and immunofluorescence staining. Histological staining revealed that elevated lactate levels, increased Pan Kla expression, and upregulated extent of M2 phenotype macrophage infiltration in clinical pulpitis specimens. Notably, we identified a positive correlation between Pan Kla levels and M2 macrophage markers. Invitro inflammatory dental pulp microenvironment model, we demonstrated that M1 macrophages actively uptake lactate from iCM, leading to increased lactylation and subsequent M2-like polarisation. Importantly, we found that iCM could regulate polarisation of M1 macrophages via metabolic reprogramming, as evidenced by RNA sequencing. Our integrated analyses revealed significant mitochondrial structural remodelling, while metabolic flux assays demonstrated a characteristic shift from glycolytic metabolism to oxidative phosphorylation. This metabolic reprogramming was functionally linked to M2 polarisation, as evidenced by phenotypic marker analysis. Moreover, iCM treatment significantly downregulated pro-inflammatory cytokine (IL-6) while upregulating anti-inflammatory marker (CD206) in experimental pulpitis models. This study revealed that elevated lactate production in the inflammatory microenvironment roles as a mediator of immunometabolic crosstalk, bridging dental pulp cells-macrophage communication. And the mechanism involved in lactylation induced metabolic reprogramming. This helps to better understand the repair potential of inflamed dental pulp, supporting biologically-based preservation approaches.

This article examines women's charitable ministry in the Russian Empire using the example of social and medical practices of women's religious communities. This phenomenon was not publicly covered in the post-reform Russian society, but, as the authors managed to establish, it was widespread throughout the Empire. The social and medical ministry of the women's convents helped to solve the urgent problems of local and rural communities. Nuns and novices provided social, spiritual and medical assistance to the most vulnerable groups — widows, unmarried elderly women, crippled and poor people, orphans. The authors expand the concept of “women's charitable subjectivity” through the use of interdisciplinary methodology, which implies the optics of the “mutual influence” of medicine and religion in historical research. In the study of women's charity, we involve the historiography of the social history of medicine and the history of women's religiosity in the Russian Empire. This perspective allowed us to discover and research the socio-medical practices of women's communities (cloisters). The authors tried to fit this plot into the social context of the history of zemskaya (“zemstvo”) medicine, social reforms and the specifics of the secularization of post-reform Russian Empire. The search-problematic nature of the article allows us to examine the place of female subjectivity — both medical and religious — from the perspective of the complex processes of modernization of society in the Russian Empire in the second half of the 19th — early 20th centuries.

When announcing the Sveriges Riksbank Prize in Economic Sciences in Memory of Alfred Nobel 2021, the Royal Swedish Academy emphasized how conclusions about cause and effect can be drawn from natural experiments. But what can dental research learn from this? The economist’s toolbox provides a number of methods for causal inference from observational data such as instrumental variables, regression discontinuity designs, or difference-in-differences analyses. Although the relevance of improving causal inference in dental research has repeatedly been highlighted in recent years, dental research still seems to reveal major room for improvement in the application of such methods. First, there seems to be an absence of causal literature on key essential research questions for oral health. Second, the diversity and diffusion of causal inferential methods in the dental literature seem very limited so far. Third, while dental research has widely been promoting the use of directed acyclic graphs (DAGs) to help conceptualize causal thinking, comparably little attention seems to have been paid to choosing and applying appropriate data-analytic approaches for causal inference. Fourth, similar to other fields of medicine, confusion seems to persist within the dental research community as to the use of causal language. If dental research is to secure a robust evidence base for promoting effective oral health interventions, we argue that dental research needs to move beyond its current methodological echo chamber and embrace a radically different approach to causal inference. We call for editors, reviewers, and authors to embrace a much more critically reflective approach to causal inference.