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Objectives: The aim of the study was to evaluate the effect of injectable platelet-rich fibrin (i-PRF) on gingival thickness and gingival recession in individuals with thin periodontal phenotypes. Method and materials: In this prospective study, i-PRF was applied via a semisurgical method to augment 53 tooth regions with thin periodontal phenotypes. In order to ensure that sufficient blood clot formed on the side of the gingiva facing the bone and that i-PRF reached the area, a minimal incision was made with the help of a scalpel in the apical region of the relevant region, and the periosteum was elevated with a microsurgical instrument. To ensure sustained exposure to angiogenetic growth factors and enhance the histoconductive properties, i-PRF injection was applied to the relevant areas in foursessions at 10-dayintervals. Results: An increase in gingival thickness was achieved in 92.5% of the areas treated with i-PRF, and the desired gingival thickness (0.8 mm) was achieved in 44.9% of these areas. In addition, significant reductions in the amount of recession were observed in 83.3% of the 12 gingival recession areas (P= .005). Moreover, complete coverage was achieved in 60% of these regions. Conclusion: With the new i-PRF semisurgical method, it was shown that gingival thickness can be increased in tooth regions with thin gingiva, andthat areas of gingival recession can be covered. Further comprehensive studies are needed to fully understand the role of i-PRF in enhancing angiogenesis and the histoconductive properties of this fully autogenous blood concentrate. [ABSTRACT FROM AUTHOR]

Objectives: Work in animal models has implicated excessive occlusal forces and occlusal trauma as co-destructive factors for periodontitis. The main aim of the present study was to make a radiographic assessment of the effects of excessive occlusal forces, ie occlusal/incisal tooth wear, widening of the periodontal space, and the presence of a mandibular torus, on interproximal marginal bone loss in a large series of patients. A secondary aim was to evaluate the statistical correlation between the parameters in two specific teeth and those of 12 teeth for marginal bone loss and six teeth for occlusal/incisal tooth wear within the same individual. Method and materials: A total of 1,950 full-mouth radiographic surveys were analyzed retrospectively. Interproximal marginal bone loss was quantified relative to the root length (Schei ruler technique). In addition, occlusal/incisal tooth wear and periodontal ligament space widening of the periodontal space were assessed, as well as the presence of a mandibular torus. Odds ratio and logistic regression analysis were used to determine the association between occlusal trauma and marginal bone loss. Results: The correlation of the measured parameters between the values for specific teeth and the whole dentition was evaluated from data from the first 400 radiographs. Teeth 41 and 33 showed the best correlation to the whole dentition: 0.85 for interproximal marginal bone loss, 0.83 for widening of the periodontal space, and 0.97 forocclusal/incisal tooth wear. The results of a logistic regression analysis with age as an independent variable, revealed a significant association between bone loss and both tooth wear (odds ratio = 2.767) and bone loss and widening of the periodontal space (odds ratio = 2.585). Conclusion: Tooth wear was positively correlated to both widening of the periodontal space and marginal bone loss. No correlation was found between the presence of a mandibular torus and marginal bone loss. [ABSTRACT FROM AUTHOR]

Partial extraction therapy (PET) is a group of surgical techniques that preserve the periodontium and peri-implant tissues during restorative and implant therapy by conserving a portion of the patient's own root structure to maintain the blood supply, derived from the periodontal ligament complex. PET includes the socket shield technique (SST), proximal shield technique (PrST), pontic shield technique (PtST), and root submergence technique (RST). Although their clinical success and benefits have been demonstrated, several studies report possible complications. The focus of this article is to highlight management strategies for the most common complications associated with PET, including internal root fragment exposure, external root fragment exposure, and root fragment mobility. [ABSTRACT FROM AUTHOR]

The recent development of nanobiomaterials has shed some light on the field of periodontal tissue regeneration. Laponite (LAP), an artificially synthesized two-dimensional (2D) disk-shaped nanosilicate, has garnered substantial attention in regenerative biomedical applications owing to its distinctive structure, exceptional biocompatibility and bioactivity. This study endeavors to comprehensively evaluate the influence of LAP on periodontal regeneration. The effects of LAP on periodontal ligament cells (PDLCs) on osteogenesis, cementogenesis and angiogenesis were systematically assessed, and the potential mechanism was explored through RNA sequencing. The results indicated that LAP improved osteogenic and cementogenic differentiation of PDLCs, the regulatory effects of LAP on PDLCs were closely correlated with activation of PI3K-AKT signaling pathway. Moreover, LAP enhanced angiogenesis indirectly via manipulating paracrine of PDLCs. Then, LAP was implanted into rat periodontal defect to confirm its regenerative potential. Both micro-CT and histological analysis indicated that LAP could facilitate periodontal tissue regeneration in vivo. These findings provide insights into the bioactivity and underlying mechanism of LAP on PDLCs, highlighting it might be a potential therapeutic option in periodontal therapy. [ABSTRACT FROM AUTHOR]

This study aimed to compare the effects of photobiomodulation therapy (PBMT) with 660 and 980 nm diode lasers on differentiation of periodontal ligament mesenchymal stem cells (PDLMSCs). In this in vitro, experimental study, PDLMSCs were obtained from the Iranian Genetic Bank and cultured in osteogenic medium. They were then subjected to irradiation of 660 and 980 nm diode lasers, and their viability was assessed after one, two, and three irradiation cycles using the methyl thiazolyl tetrazolium (MTT) assay. The cells also underwent DAPI staining, cell apoptosis assay by using the Annexin V/PI, Alizarin Red staining, and real-time polymerase chain reaction (PCR) for assessment of the expression of osteogenic genes. Data were analyzed by two-way ANOVA. The two laser groups had no significant difference in cell apoptosis according to the results of DAPI staining. Both laser groups showed higher cell viability in the MTT assay at 4 and 6 days compared with the control group. Annexin V/PI results showed higher cell viability in both laser groups at 4 days compared with the control group. Rate of early and late apoptosis was lower in both laser groups than the control group at 4 days. Necrosis had a lower frequency in 980 nm laser group than the control group on day 6. Alizarin Red staining showed higher cell differentiation in both laser groups after 3 irradiation cycles than the control group. The highest expression of osteopontin (OPN), osteocalcin (OCN), and Runt-related transcription factor 2 (RUNX2) was noted in 660 nm laser group with 3 irradiation cycles at 14 days, compared with the control group. PBMT with 660 and 980 nm diode lasers decreased apoptosis and significantly increased PDLMSC differentiation after 3 irradiation cycles. [ABSTRACT FROM AUTHOR]

PurposeMaterials and MethodsResultsConclusionsPeriodontal ligament cells (PDLCs) play a significant role in orthodontic force induced bone remodeling. However, the molecular mechanisms by which PDLCs respond to mechanical stimuli and influence osteoclastic activities remain unclear. This study aims to investigate the role of UCHL1, a key deubiquitinating enzyme involved in protein degradation and cellular responses, in force-treated PDLCs during orthodontic tooth movement (OTM).In this study, we conducted in vivo and in vitro experiments using human PDLCs and a rat model of OTM. Mechanical stress was applied to PDLCs, and UCHL1 expression was analyzed through quantitative real-time polymerase chain reaction (qPCR), Western blot, and immunofluorescence staining. UCHL1 knockdown was achieved using siRNA, and its effects on osteoclast differentiation were assessed. The role of the MAPK/ERK pathway was investigated using the MEK-specific inhibitor U0126. An animal model of OTM was established, and the impact of UCHL1 inhibitor-LDN57444 on OTM and osteoclastic activity was evaluated through micro-CT analysis, histological staining, and immunohistochemistry.Mechanical force induced UCHL1 expression in PDLCs during OTM. UCHL1 knockdown downregulated the RANKL/OPG ratio in PDLCs, affecting osteoclast differentiation. LDN57444 inhibited OTM and osteoclastic activity. UCHL1 activation correlated with ERK1/2 phosphorylation in force-treated PDLCs.Mechanical force mediated UCHL1 activation in PDLCs promotes osteoclast differentiation via the ERK1/2 signaling pathway during OTM. [ABSTRACT FROM AUTHOR]

Background: Here, we evaluated whether the histone lysine demethylase 5B (JARID1B), is involved in osteogenic phenotype commitment of periodontal ligament cells (PDLCs), by considering their heterogeneity for osteoblast differentiation. Materials and Methods: Epigenetic, transcriptional, and protein levels of a gene set, involved in the osteogenesis, were investigated by performing genome‐wide DNA (hydroxy)methylation, mRNA expression, and western blotting analysis at basal (without osteogenic induction), and at the 3rd and 10th days of osteogenic stimulus, in vitro, using PDLCs with low (l) and high (h) osteogenic potential as biological models. Results: h‐PDLCs showed reduced levels of JARID1B, compared to l‐PDLCs, with significant inversely proportional correlations between RUNX2 and RUNX2/p57. Epigenetically, a significant reduction in the global H3K4me3 content was observed only in h‐PDLCs. Immunoblotting data reveal a significant reduction in the global H3K4me3 content, at 3 days of induction only in h‐PDLCs, while an increase in the global H3K4me3 content was observed at 10 days for both PDLCs. Additionally, positive correlations were found between global H3K4me3 levels and JARID1B gene expression. Conclusions: Altogether, our results show the crucial role of JARID1B in repressing PDLCs osteogenic phenotype and this claims to pre‐clinical protocols proposing JARID1B as a potential therapeutic target. [ABSTRACT FROM AUTHOR]

This study explores the potential role and mechanism of Ginsenoside Rb3 (Rb3) in modulating osteoclastogenesis induced by human periodontal ligament fibroblasts (hPLFs) within the periodontitis microenvironment. We investigated the anti‐inflammatory effects of Rb3 on hPLFs stimulated with Porphyromonas gingivalis lipopolysaccharide (P.g‐LPS) utilizing quantitative polymerase chain reaction (qPCR) and enzyme‐linked immunosorbent assay techniques. Moreover, the functional role of Rb3 in hPLFs‐induced osteoclast formation was assessed by treating human bone marrow‐derived macrophages (hBMMs) with conditioned medium from hPLFs, followed by analyses through qPCR, western blot analysis, and staining for tartrate‐resistant acid phosphatase (TRAP) and phalloidin. The impact of Rb3 on the activation of the STAT3 signaling pathway was determined via western blot analysis. Results indicated that Rb3 treatment significantly suppressed the upregulation of pro‐inflammatory cytokines (TNF‐α, IL‐1β, IL‐6, MCP‐1, and IL‐18) at both gene and protein levels in hPLFs induced by P.g‐LPS. Furthermore, conditioned medium from Rb3 plus P.g‐LPS treated hPLFs notably decreased the number of TRAP‐positive cells, actin ring formations, and the expression of osteoclast marker genes (including CTSK, NFATC1, and ACP5). Rb3 also inhibited the P.g‐LPS‐induced activation of the STAT3 pathway, with the activation of STAT3 partially reversing the effects of Rb3 on inflammation and osteoclast differentiation. Collectively, Rb3 ameliorates inflammation in P.g‐LPS‐stimulated hPLFs and reduces hPLFs‐induced osteoclastogenesis by inhibiting the STAT3 signaling pathway, suggesting its potential as a therapeutic agent for periodontitis. Highlights: Ginsenoside Rb3 reduces inflammation in human periodontal ligament fibroblasts in a periodontitis microenvironment.Ginsenoside Rb3 inhibits the formation of osteoclasts mediated by human periodontal ligament fibroblasts.The effect of Ginsenoside Rb3 on the inflammation of human periodontal ligament fibroblasts and osteoclast formation is related to the inhibition of the STAT3 pathway. [ABSTRACT FROM AUTHOR]

Background and Aims: Idiopathic osteosclerosis is an asymptomatic local growth of cortical bone and is discovered incidentally on panoramic radiographs. The purpose of this study is to evaluate the frequency of idiopathic osteosclerosis and its radiographic features in panoramic images of patients referred to the Department of Maxillofacial Radiology, Faculty of Dentistry, Arak University of Medical Sciences (Iran) in 2022-2023. Materials and Methods: In this cross-sectional study, 460 panoramic images from the radiology department of Arak Faculty of Dentistry were randomly selected and analyzed. The demographic information of patients, frequency of idiopathic osteosclerosis, location, and also its relationship with adjacent teeth in terms of proximity to lamina dura and periodontal ligament and radiographic features in terms of size and morphology were evaluated. The data were analyzed using the SPSS24 software. Results: Panoramic images of 460 patients (266 men and 194 women) with an average age of 38.12 (11.75) years were evaluated. The frequency of idiopathic osteosclerosis was 6.1% (28 images). 92.9% of the lesions were in the lower jaw and 46.4% of them were near the premolar teeth. In 39.3% of the cases, the lesion was adjacent to the periodontal ligament and laminadora of the tooth. In 3.6% of the cases, it was associated with a small displacement of the adjacent tooth, and 17.9% was associated with tooth root resorption. According to the results, there was no correlation between the incidence of this lesion with age and gender (P>0.05). Conclusion: According to the findings of this study, the frequency of idiopathic osteosclerosis in the patients referred to Arak dental school was reported as 6.1%. Most of these lesions were observed in the back of the lower jaw and thus, it is important to be able to distinguish this lesion from the radiopaque lesions of the jaw which need treatment. [ABSTRACT FROM AUTHOR]

Mechanical forces affect periodontal health through multiple mechanisms. Normally, mechanical forces can boost soft and hard tissue metabolism. However, excessive forces may damage the periodontium or result in irreversible inflammation, whereas absence of occlusion forces also leads to tissue atrophy and bone resorption. We systemically searched the PubMed and Web of Science databases and found certain mechanisms of mechanical forces on immune defence, extracellular matrix (ECM) metabolism, specific proteins, bone metabolism, characteristic periodontal ligament stem cells (PDLSCs) and non-coding RNAs (ncRNAs) as these factors contribute to periodontal homeostasis. The immune defence functions change under forces; genes, signalling pathways and proteinases are altered under forces to regulate ECM metabolism; several specific proteins are separately discussed due to their important functions in mechanotransduction and tissue metabolism. Functions of osteocytes, osteoblasts, and osteoclasts are activated to maintain bone homeostasis. Additionally, ncRNAs have the potential to influence gene expression and thereby, modify tissue metabolism. This review summarizes all these mechanisms of mechanical forces on periodontal homeostasis. Identifying the underlying causes, this review provides a new perspective of the mechanisms of force on periodontal health and guides for some new research directions of periodontal homeostasis. [ABSTRACT FROM AUTHOR]

Regenerating inflamed bone defects represents a severe clinical challenge due to the undesirable inflammatory microenvironment. The inflammatory stimulus poses a weighty threat to the regenerative capacity of endogenously derived mesenchymal stem cells (MSCs), which are mainly responsible for osteogenic differentiation, thereby resulting in compromised endogenous bone formation. Consequently, alleviating the biological characteristics of inflammatory-impaired MSCs is crucial for promoting inflamed bone regeneration. Nano-sized small extracellular vesicles (sEVs) have emerged as promising therapeutic tools to orchestrate MSCs fate due to their intrinsic biocompatibility and encapsulated bioactive contents. In the present study, we extracted sEVs from youthful and adult dental pulp MSCs and explored their ability to recover inflammation-compromised periodontal ligament stem cells (IPDLSCs). The results indicated that both types of sEVs were capable of facilitating IPDLSCs osteogenesis. However, young sEVs exhibited a more robust potential at a lower concentration compared to adult sEVs. Mechanically, young sEVs enhanced the expression of bone morphogenetic protein 4 (BMP4) via delivering the protein Biglycan, which correspondingly promoted the osteogenic capability of IPDLSCs. Collectively, our findings emphasized that young sEVs hold enormous potential to rescue the inherent function and regenerative competence of inflammation-impaired MSCs, shedding light on their promising therapeutic prospects for infected bone regeneration. [ABSTRACT FROM AUTHOR]

Background: Micro-osteoperforation is a minimally invasive technique aimed at accelerating tooth movement. The goal of this novel experimental study was to assess tooth movement and stress distribution produced by the force of orthodontic movement on the tooth structure, periodontal ligament, and maxillary bone structure, with and without micro-osteoperforation, using the finite element method. Materials and methods: Cone-beam computed tomography was used to obtain a virtual model of the maxilla and simulate the extraction of right and left first premolars. Three micro-osteoperforations (1.5 x 5 mm) were made in the hemiarch on the distal and mesial surfaces of upper canines, according to the power tip geometry of the Propel device (Propel Orthodontics, Ossining, New York, USA). An isotropic model of the maxilla was fabricated according to the finite element method by insertion of mechanical properties of the tooth structures, with orthodontic force (1.5 N) simulation in the distal movement on the upper canine of a hemiarch. Results: Initial movement was larger when micro-osteoperforations were performed on the dental crown (24%) and on the periodontal ligament (29%). In addition, stress distribution was higher on the bone structure (31%) when micro-osteoperforations were used. Conclusions: Micro-osteoperforations considerably increased the movement of both the dental crown and periodontal ligament, which highlights their importance in the improvement of orthodontic movement, as well as in stress distribution across the bone structure. Important stress absorption regions were identified within micro-osteoperforations. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effects of the estrogen depression during orthodontic tooth movement on alveolar bone microarchitecture and periodontal ligament. Female Wistar rats were divided into two groups, one consisting of non‐ovariectomized animals subjected to orthodontic tooth movement, and one comprising ovariectomized animals subjected to orthodontic tooth movement. Micro‐CT assessment of bone volume to total volume (BV/TV), total porosity, trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular separation (Tb.Sp) in the alveolar bone of the orthodontically moved tooth was performed. Histomorphometric analyses were made in the periodontal ligament, and immunoexpression of RANK, RANKL, OPG, and TUNEL were quantified. Orthodontic tooth movement in the group of ovariectomized rats was faster than in non‐ovariectomized animals. The alveolar bone area showed lower values of BV/TV and trabecular thickness, and higher bone porosity and trabeculae numbers in the ovariectomized rats. Histological analyses in the ovariectomized group revealed an increase in collagen fibers in the periodontal ligament. The apoptotic cell counts in the periodontal ligament were higher in the group of ovariectomized rats than in the sham‐operated rats. Ovariectomy resulted in an increase in tooth movement and alteration of the alveolar bone microstructure in the first 7 day of orthodontic tooth movement, and in the presence of apoptotic cells in the periodontal ligament. [ABSTRACT FROM AUTHOR]

The periodontium is a complex hierarchical structure composed of alveolar bone, periodontal ligament, cementum, and gingiva. Periodontitis is an inflammatory disease that damages and destroys the periodontal tissues supporting the tooth. Periodontal therapies aim to regenerate the lost tissues, yet current treatments lack the integration of multiple structural/biochemical instructive cues to induce a coordinated regeneration, which leads to limited clinical outcomes. Hierarchical biomaterial scaffolds offer the opportunity to recreate the organization and architecture of the periodontium with distinct compartments, providing structural biomimicry that facilitates periodontal regeneration. Various scaffolds have been fabricated and tested preclinically, showing positive regenerative results. This review provides an overview of the recent research on hierarchical scaffolds for periodontal tissue engineering (TE). First, the hierarchical structure of the periodontium is described, covering the limitations of the current treatments used for periodontal regeneration and presenting alternative therapeutic strategies, including scaffolds and biochemical factors. Recent research regarding hierarchical scaffolds is highlighted and discussed, in particular, the scaffold composition, fabrication methods, and results from in vitro/in vivo studies are summarized. Finally, current challenges associated with the application of hierarchical scaffolds for periodontal TE are debated and future research directions are proposed. [ABSTRACT FROM AUTHOR]

Background: Orthodontic tooth movement (OTM) is a dynamic equilibrium of bone remodeling, involving the osteogenesis of new bone and the osteoclastogenesis of old bone, which is mediated by mechanical force. Periodontal ligament stem cells (PDLCSs) in the periodontal ligament (PDL) space can transmit mechanical signals and regulate osteoclastogenesis during OTM. KAT6A is a histone acetyltransferase that plays a part in the differentiation of stem cells. However, whether KAT6A is involved in the regulation of osteoclastogenesis by PDLSCs remains unclear. Results: In this study, we used the force-induced OTM model and observed that KAT6A was increased on the compression side of PDL during OTM, and also increased in PDLSCs under compression force in vitro. Repression of KAT6A by WM1119, a KAT6A inhibitor, markedly decreased the distance of OTM. Knockdown of KAT6A in PDLSCs decreased the RANKL/OPG ratio and osteoclastogenesis of THP-1. Mechanistically, KAT6A promoted osteoclastogenesis by binding and acetylating YAP, simultaneously regulating the YAP/TEAD axis and increasing the RANKL/OPG ratio in PDLSCs. TED-347, a YAP-TEAD4 interaction inhibitor, partly attenuated the elevation of the RANKL/OPG ratio induced by mechanical force. Conclusion: Our study showed that the PDLSCs modulated osteoclastogenesis and increased the RANKL/OPG ratio under mechanical force through the KAT6A/YAP/TEAD4 pathway. KAT6A might be a novel target to accelerate OTM. [ABSTRACT FROM AUTHOR]

The periodontal ligament plays a significant role in orthodontic and masticatory processes. To explicitly investigate the effects of dynamic force amplitude and frequency on the dynamic tensile properties of the periodontal ligament, in vitro tensile experiments were conducted using a dynamic mechanical analysis at various dynamic force amplitudes across a wide frequency range. Storage modulus, loss modulus, and loss factor values were measured. A Maxwell constitutive model based on modulus was established to describe the dynamic mechanical properties of the periodontal ligament. The results showed that the storage modulus ranged from 29.53 MPa to 158.24 MPa, the loss modulus ranged from 3.26 MPa to 76.16 MPa, and the loss factor values all increased with higher frequencies and higher dynamic force amplitudes. Based on the parameters obtained from the fitting results, it is evident that the short‐term response has a more pronounced impact on the elastic response of the periodontal ligament than the long‐term response. Increasing the dynamic force amplitude and its frequency amplified the viscous effects of the periodontal ligament and enhanced energy dissipation. The proposed constitutive model further demonstrated that the periodontal ligament acts as a viscoelastic biomaterial. These findings have implications for future research on the periodontal ligament. [ABSTRACT FROM AUTHOR]

Non-coding RNA has many types which has rich functions and plays an important role in the study of basic molecular mechanisms. Many non-coding RNA have important implications for pluripotent stem cells and embryonic stem cells. It has been found to affect the self-renewal and osteogenesis of many types of stem cells. They have also been found to regulate stem cell proliferation and induct bone differentiation. Periodontal ligament stem cells are essential for the regeneration of periodontal tissue. In recent years, in the field of stomatology, studies have found that many non-coding RNA also have significant regulatory effects on the proliferation and differentiation of periodontal stem cells and may become potential therapeutic targets for many common periodontal diseases such as periodontitis, bone/tooth/soft tissue loss and orthodontic treatment. Therefore, we summarized the current research status of non-coding RNA in the field of molecular mechanism of periodontal ligament stem cells and prospected its future progress. [ABSTRACT FROM AUTHOR]

The periodontal tissue is made up of supporting tissues and among its functions, it promotes viscoelastic properties, proprioceptive sensors, and dental anchorage. Its progressive destruction by disease leads to the loss of bone and periodontal ligaments. For this reason, biomaterials are constantly being developed to restore tissue function. Various techniques are being used to promote regenerative dentistry, including 3D bioprinting with bioink formulations. This paper aims to review the different types of bioink formulations and 3D bioprinting techniques used in periodontal tissue regeneration. Different techniques have been formulated, and the addition of different materials into bioinks has been conducted, with the intention of improving the process and creating a bioink that supports cell viability, proliferation, differentiation, and stability for periodontal tissue regeneration. [ABSTRACT FROM AUTHOR]

Periodontis is a chronic inflammatory disease induced by periodontopathogenic bacteria. The excessive immune response caused by persistent bacterial infection leads to alveolar bone resorption and ultimately tooth loss. Cardamonin is a biologically active substance that is found in the Zingiberaceae family, such as Alpinia zerumbet, and is classified as a natural chalcone. There have been no attempts to use cardamonin for the treatment of periodontitis, and no reports have examined the effects of cardamonin on periodontal tissue component cells. The aim of this study was to analyze effects of cardamonin on expression of inflammation mediators produced by TNFα-stimulated human periodontal ligament cells (HPDLCs), including its effects on signal transduction molecules. Cytokine and chemokine levels were measured by ELISA. Protein expression in HPDLCs and activations of signal transduction pathway were determined by Western blotting. Our results indicate that cardamonin suppresses C-C motif chemokine ligand (CCL)2, CCL20, C-X-C motif chemokine ligand (CXCL)10, and interleukin (IL)-6 production and intercellular adhesion molecule (ICAM)-1 and cyclooxygenase (COX)-2 expression in TNF-α-stimulated HPDLCs. In addition, cardamonin induced the expression of the antioxidant enzyme, Heme Oxygenase (HO)-1, in HPDLCs. Furthermore, cardamonin suppressed TNF-α-stimulated c-Jun N-terminal kinase (JNK), nuclear factor (NF)-κB, and signal transducer and activator of transcription (STAT)3 signaling pathways in HPDLCs. We show that cardamonin reduces inflammatory mediator production by inhibiting the activation of several signaling pathways in this manuscript. [ABSTRACT FROM AUTHOR]

The periodontal ligament (PDL) is a complex connective tissue that connects the tooth root to the dental alveolar bone and plays crucial mechanical roles. PDL also exhibits regenerative roles and regulatory functions to maintain periodontium integrity and homeostasis. While PDL exposure to oral microbial pathogens is common, virtually nothing is known regarding viral infections of PDL. In particular, human herpes simplex virus type 1 (HSV-1) persistently infects the oral cavity through infections of the oral epithelium, connective tissue and neurons. While the oral spread of HSV-1 is generally asymptomatic, this virus has also been implicated in various oral pathologies. In this study, using a primary cell model derived from PDL (PDL cells), and whole surgical fragments of PDL, we provide evidence supporting the efficient infection of PDL by HSV-1 and the promotion of cytopathic effects. Infection of PDL by HSV-1 was also associated with an acute innate inflammatory response, as illustrated by the production of antiviral interferons and pro-inflammatory cytokines. Furthermore, this inflammatory response to HSV-1 was exacerbated in the presence of bacterial-derived products, such as peptidoglycans. This work therefore highlights the ability of HSV-1 to infect mesenchymal cells from PDL, suggesting that PDL may serve as a viral reservoir for the periodontal spread of HSV-1. Moreover, this raises questions about HSV-1 oral pathogenesis, as HSV-1-associated cytopathic and inflammatory effects may contribute to profound alterations of PDL integrity and functioning. [ABSTRACT FROM AUTHOR]

Objectives: To assess the biocompatibility, bioactivity, and immunomodulatory properties of three new calcium silicate cement-based sealers: Ceraseal (CS), Totalfill BC Sealer (TFbc) and WellRoot ST (WR-ST) on human periodontal ligament stem cells (hPDLSCs). Materials and methods: HPDLSCs were isolated from extracted third molars from healthy patients. Eluates (1:1, 1:2, and 1:4 ratio) and sample discs of CS, TFbc and WR-ST after setting were prepared. A series of assays were performed: cell characterization, cell metabolic activity (MTT assay) cell attachment and morphology (SEM assay), cell migration (wound-healing assay), cytoskeleton organization (phaloidin-based assay); IL-6 and IL-8 release (ELISA); differentiation marker expression (RT-qPCR assay), and cell mineralization (Alizarin Red S staining). HPDLSCs cultured in unconditioned (negative control) or osteogenic (positive control) culture media were used as a comparison. Statistical significance was established at p < 0.05. Results: All the tested sealers exhibited similar results in the cytocompatibility assays (cell metabolic activity, migration, attachment, morphology, and cytoskeleton organization) compared with a negative control group. CS and TFbc exhibited an upregulation of at least one osteo/cementogenic marker compared to the negative and positive control groups. CS and TFbc also showed a significantly higher calcified nodule formation than the negative and positive control groups. Both the marker expression and calcified nodule formation were significantly higher in CS-treated cells than TFbc treated cells. WR-ST exhibited similar results to the control group. CS and TFbc-treated cells exhibited a significant downregulation of IL-6 after 72 h of culture compared to the negative control group (p < 0.05). Conclusion: All the tested sealers exhibited an adequate cytocompatibility. CS significantly enhances cell differentiation by upregulating the expression of key genes associated with bone and cementum formation. Additionally, CS was observed to facilitate the mineralization of the extracellular matrix effectively. In contrast, the effects of TFbc and WR-ST on these processes were less pronounced compared to CS. Furthermore, both CS and TFbc exhibited an anti-inflammatory potential, contributing to their potential therapeutic benefits in regenerative endodontics. Clinical relevance: This is the first study to compare the biological properties and immunomodulatory potential of Ceraseal, Totalfill BC Sealer, and WellRoot ST. The results act as supporting evidence for their use in root canal treatment. [ABSTRACT FROM AUTHOR]

Background: The study evaluates the feasibility of employing the radiographic visibility of the root pulp and periodontal ligament in mandibular molars for age estimation, particularly focusing on the 18 years of age threshold. This study additionally investigates the potential of root canal width reduction in mandibular molars, as a reliable method for forensic age estimation in living individuals. Materials and methods: A cross-sectional study was conducted to assess the radiographic visibility of the root pulp (RPV) and the root canal width (RCW) of mandibular first, second, and third molars along with the radiographic visibility of the periodontal ligament (PLV) of mandibular third molars, in a sample of 403 individuals aged 16-25 years (220 males and 183 females). Data regarding age for different stages of RPV and PLV and various types of RCW were recorded and observed for sex-based differences. Results obtained were tabulated and descriptive statistics were applied to summarise the findings. Results: Individuals over 18 years old were classified with higher accuracy using stage 3 of the RPV scoring system in all mandibular molars (first, second, and third) compared to stage 2, which was also effective for the second and third molars. This result held regardless of sex and side examined. Additional l y, root canal width (RCW) a ssessment demonstrated that individuals with RCW types A, B, and C were more likely to be under 18 years old in both sexes. Conversely, individuals with RCW type U on the right side for males and the left side for females exhibited a higher likelihood of being above 18 years old. Conclusion: The study suggests that the assessment of mandibular molars could potentially serve as an auxiliary tool in age estimation methods, particularly for approximating individuals around the 18 years of age threshold. Further investigation is warranted to explore the potential application of root canal width measurements in forensic age estimation. [ABSTRACT FROM AUTHOR]

Restoring periodontally compromised teeth in esthetic zones through dental implant rehabilitation poses significant challenges due to the loss of supporting tissues. This case report describes a staged treatment strategy designed for a 48-year-old woman with advanced chronic periodontitis of the esthetic zone. This approach combined various advanced techniques, including periodontal regeneration, orthodontic implant site development with labial root torque, guided bone regeneration, and soft tissue augmentation. The innovative orthodontic implant site development with labial root torque technique was employed to harness healthy palatal periodontal ligament cells by strategically applying labial root torque in the horizontal labial-palatal direction. This technique uses healthy palatal periodontal ligament cells, which benefits overall periodontal health. The procedure involved gradually shifting hopeless teeth at a rate of 2 mm per month using nickel-titanium wires, thereby maintaining overcorrection for 2 months before extraction. Following successful orthodontic implant site development with labial root torque, the next phase involved guided bone regeneration using a honeycomb-structured titanium membrane. This set the stage for implant placement 6 months later, ensuring a stable foundation for subsequent prosthetic intervention. Soft tissue augmentation was then meticulously performed using an artificial collagen dermis infused with fibroblast growth factor-2, contributing to the overall esthetic outcome. Final prosthesis integration revealed a harmonious blend with the adjacent teeth and gums, underscoring the success of this multidisciplinary approach. This case report provides valuable insights into severe periodontitis in the esthetic field. Our findings highlight the importance of continuously researching and improving procedures for optimal patient care. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether visceral adipose tissue‐derived serine protease inhibitor (vaspin) can alleviate the inhibitory effect of high‐glucose (HG) culture on the proliferation and osteogenic differentiation of human periodontal ligament stem cells (PDLSCs) and to preliminarily explore the underlying mechanisms. Background: High glucose produces damage to the regeneration of periodontal tissue of PDLSCs. The expression level of vaspin in periodontal tissue is high in periodontitis patients and effectively reduced after initial therapy of periodontal diseases. However, the effect of vaspin on PDLSCs remains unknown. Materials and Methods: PDLSCs were cultured in media augmented with 5.5 or 25.0 mM concentrations of glucose to elucidate the impact and mechanism of vaspin on PDLSCs under high glucose in vitro. Proliferation was measured by Cell Counting Kit‐8 (CCK8) assay. Osteogenesis of PDLSCs was assessed by alkaline phosphatase (ALP) staining, ALP activity, and Alizarin Red staining. Quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blot (WB) were used to investigate the osteo‐specific markers. Then, the molecular impact of vaspin in the presence/absence of HG on PDLSCs physiology was determined with TGF‐β1/Smad signaling pathway as the main focus. Results: It was revealed that the proliferation and osteogenic differentiation (OD) of PDLSCs under HG was reduced, and by adding vaspin the anti‐osteogenic impact of HG was relieved. Moreover, vaspin enhanced TGF‐β1/Smad signaling pathway activity. Pretreatment with TGF‐β1 inhibitor blocked vaspin‐triggered TGF‐β1/Smad signal activation and minimized the vaspin‐induced protective effect against HG‐inhibited growth and OD. Conclusions: In summary, vaspin observably reduces HG‐mediated inhibition of PDLSCs OD by modulating the TGF‐β1/Smad signaling pathway. Vaspin may be a potential therapeutic for periodontal tissue regeneration in diabetic patients. [ABSTRACT FROM AUTHOR]

Background and Objective: Prevention of periodontal bone resorption triggered by Porphyromonas gingivalis (P. gingivalis) is crucial for dental stability. Capsaicin, known as the pungent ingredient of chili peppers, can activate key signaling molecules involved in osteogenic process. However, the effect of capsaicin on osteogenesis of periodontal ligament stem cells (PDLSCs) under inflammation remains elusive. Methods: P. gingivalis culture suspension was added to mimic the inflammatory status after capsaicin pretreatment. The effects of capsaicin on the osteogenesis of PDLSCs, as well as mitochondrial morphology, Ca2+ level, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and osteogenesis‐regulated protein expression levels were analyzed. Furthermore, a mouse experimental periodontitis model was established to evaluate the effect of capsaicin on alveolar bone resorption and the expression of osteogenesis‐related proteins. Results: Under P. gingivalis stimulation, capsaicin increased osteogenesis of PDLSCs. Not surprisingly, capsaicin rescued the damage to mitochondrial morphology, decreased the concentration of intracellular Ca2+ and ROS, enhanced MMP and activated phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. The in vivo results showed that capsaicin significantly attenuated alveolar bone loss and augmented the expression of bone associated proteins. Conclusion: Capsaicin increases osteogenesis of PDLSCs under inflammation and reduces alveolar bone resorption in mouse experimental periodontitis. [ABSTRACT FROM AUTHOR]

Background and Objective: The biological effects of atmospheric plasma (cold plasma) show its applicability for controlling the etiological factors that involve tissue repair. Thus, the study evaluated the effect of atmospheric plasma therapy in the control of tissue inflammation and bone remodeling in experimental periodontitis. Methods: Fifty‐six rats were subjected to ligation in the cervical region of the first maxillary molars (8 weeks). The animals were divided into two groups (n = 28): periodontitis without treatment group (P group), and periodontitis with atmospheric plasma treatment group (P + AP group). Tissue samples were collected at 2 and 4 weeks after treatment to analyze the inflammation and bone remodeling by biochemical, histomorphometric, and immunohistochemical analyses. Results: Inflammatory infiltration in the gingival and periodontal ligament was lower in the P + AP group than in the P group (p <.05). The MPO and NAG levels were higher in the P + AP group compared to P group (p <.05). At 4 weeks, the TNF‐α level was lower and the IL‐10 level was higher in the P + AP group compared to P group (p <.05). In the P + AP group, the IL‐1β level increased in the second week and decreased in the fourth week (p <.05), the number of blood vessels was high in the gingival and periodontal ligament in the second and fourth week (p <.05); and the number of fibroblasts in the gingival tissue was low in the fourth week, and higher in the periodontal tissue in both period (p <.05). Regarding bone remodeling, the RANK and RANKL levels decreased in the P + AP group (p <.05). The OPG level did not differ between the P and P + AP groups (p >.05), but decreased from the second to the fourth experimental week in P + AP group (p <.05). Conclusions: The treatment of experimental periodontitis with atmospheric plasma for 4 weeks modulated the inflammatory response to favor the repair process and decreased the bone resorption biomarkers, indicating a better control of bone remodeling in periodontal disease. [ABSTRACT FROM AUTHOR]

Static well plates remain the gold standard to study viral infections in vitro, but they cannot accurately mimic dynamic viral infections as they occur in the human body. Therefore, we established a dynamic cell culture platform, based on centrifugal microfluidics, to study viral infections in perfusion. To do so, we used human primary periodontal dental ligament (PDL) cells and herpes simplex virus-1 (HSV-1) as a case study. By microscopy, we confirmed that the PDL cells efficiently attached and grew in the chip. Successful dynamic viral infection of perfused PDL cells was monitored using fluorescent imaging and RT-qPCR-based experiments. Remarkably, viral infection in flow resulted in a gradient of HSV-1-infected cells gradually decreasing from the cell culture chamber entrance towards its end. The perfusion of acyclovir in the chip prevented HSV-1 spreading, demonstrating the usefulness of such a platform for monitoring the effects of antiviral drugs. In addition, the innate antiviral response of PDL cells, measured by interferon gene expression, increased significantly over time in conventional static conditions compared to the perfusion model. These results provide evidence suggesting that dynamic viral infections differ from conventional static infections, which highlights the need for more physiologically relevant in vitro models to study viral infections. [ABSTRACT FROM AUTHOR]

Advanced periodontitis poses a significant threat to oral health, causing extensive damage and loss of both hard and soft periodontal tissues. While traditional therapies such as scaling and root planing can effectively halt the disease's progression, they often fail to fully restore the original architecture and function of periodontal tissues due to the limited capacity for spontaneous regeneration. To address this challenge, periodontal tissue engineering has emerged as a promising approach. This technology centers on the utilization of biomaterial scaffolds, which function as three-dimensional (3D) templates or frameworks, supporting and guiding the regeneration of periodontal tissues, including the periodontal ligament, cementum, alveolar bone, and gingival tissue. These scaffolds mimic the extracellular matrix (ECM) of native periodontal tissues, aiming to foster cell attachment, proliferation, differentiation, and, ultimately, the formation of new, functional periodontal structures. Despite the inherent challenges associated with preclinical testing, the intensification of research on biomaterial scaffolds, coupled with the continuous advancement of fabrication technology, leads us to anticipate a significant expansion in their application for periodontal tissue regeneration. This review comprehensively covers the recent advancements in biomaterial scaffolds engineered specifically for periodontal tissue regeneration, aiming to provide insights into the current state of the field and potential directions for future research. [ABSTRACT FROM AUTHOR]

Periodontitis is a bacteria‐induced chronic inflammatory disease characterized by degradation of the supporting tissue and bone in the oral cavity. Treatment modalities seek to facilitate periodontal rehabilitation while simultaneously preventing further gingival tissue recession and potentially bone atrophy. The aim of this study was to compare two differently sourced membranes, a resorbable piscine collagen membrane and a porcine‐derived collagen membrane, in the repair of soft tissue defects utilizing a preclinical canine model. This in vivo component consisted of 10 beagles which were subjected to bilateral maxillary canine mucogingival flap defects, as well as bilateral soft tissue defects (or pouches) with no periodontal ligament damage in the mandibular canines. Defects received either a piscine‐derived dermal membrane, (Kerecis® Oral, Ísafjörður, Iceland) or porcine‐derived dermal membrane (Geistlich Mucograft®, Wolhusen, Switzerland) in a randomized fashion (to avoid site bias) and were allowed to heal for 30, 60, or 90 days. Statistical evaluation of tissue thickness was performed using general linear mixed model analysis of variance and least significant difference (LSD) post hoc analyses with fixed factors of time and membrane. Semi‐quantitative analysis employed for inflammation assessment was evaluated using a chi‐squared test along with a heteroscedastic t‐test and values were reported as mean and corresponding 95% confidence intervals. In both the mucogingival flap defects and soft tissue gingival pouches, no appreciable qualitative differences were observed in tissue healing between the membranes. Furthermore, no statistical differences were observed in the thickness measurements between piscine‐ and porcine‐derived membranes in the mucogingival flap defects (1.05 mm [±0.17] and 1.29 mm [±0.17], respectively [p =.06]) or soft tissue pouches (1.36 mm [±0.14] and 1.47 mm [±0.14], respectively [p =.27]), collapsed over time. Independent of membrane source (i.e., piscine or porcine), similar inflammatory responses were observed in both the maxilla and mandible at the three time points (p =.88 and p =.79, respectively). Histologic and histomorphometric evaluation results indicated that both membranes yielded equivalent tissue responses, remodeling dynamics and healing patterns for the mucogingival flap as well as the soft tissue gingival pouch defect models. [ABSTRACT FROM AUTHOR]

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Alveolar bone loss resulting from periodontal disease ultimately leads to tooth loss. Periodontal ligament mesenchymal stem cells (PDLMSCs) are the tissue-specific cells responsible for maintaining and repairing the periodontal ligament, cementum, and alveolar bone. In this study, we explored the role of aldehyde oxidase 1 (AOX1) in regulating the osteoinduction of human periodontal ligament stem cells (hPDLMSCs). hPDLMSCs were isolated from clinically healthy donors, and AOX1 expression was assessed by comparing inducted and non-inducted hPDLMSCs. Remarkably, we observed a significant upregulation of AOX1 expression during osteoinduction, while AOX1 silencing resulted in the enhanced osteogenic potential of hPDLMSCs. Subsequent experiments and analysis unveiled the involvement of retinoid X receptor (RXR) signaling in the inhibition of osteogenesis in hPDLMSCs. Ligands targeting the RXR receptor mirrored the effects of AOX1 on osteogenesis, as evidenced by alterations in alkaline phosphatase (ALP) activity and bone formation levels. Collectively, these findings underscore the potential regulatory role of AOX1 via RXR signaling in the osteogenesis of hPDLMSCs. This elucidation is pivotal for advancing hPDLMSC-based periodontal regeneration strategies and lays the groundwork for the development of targeted therapeutic interventions aimed at enhancing bone formation in the context of periodontal disease. [ABSTRACT FROM AUTHOR]

Background: The effects of traction forces at different angles on impacted central incisors(ICI)with varying inverted angles (IA) may be different. The objective of this study was to analyze the biomechanical effects of different force directions (FD) on developmentally inverted ICI with multi-angle variations and to offer insights and guidance for the treatment of inverted ICI. Methods: Three-dimensional finite element method was employed to simulate clinical scenarios of inverted ICI traction. As such, 0.2 N of force (direction: antero-superior angles of 90°, 100°, 110°, 120°, and 130° relative to the long axis of the inverted ICI crown) was applied to the inverted ICI with inverse angles (IA) of 40°, 30°, 20°, 10° and 0°. Inverted ICI apical displacement and Von Mises stress on periodontal ligament (PDL) and alveolar bone were compared. Results: IA and FD showed minimal influence on the stress distribution in the PDL, as higher stresses were concentrated in the apical region. The higher stresses in the alveolar bone are focused on the cervical and apical regions of the tooth. In particular, IA exerts a more significant impact on stress distribution in the alveolar bone than FD. The influence of IA on the apical displacement of inverted ICI is larger than that of FD. Conclusions: To promote the health of the root and periodontal tissues, it is recommended to use an angle of 100°-110° relative to the long axis of the ICI crown when dealing with a large IA (> 20°) developmentally inverted ICI. Conversely, an angle of 110°-120° can be used. [ABSTRACT FROM AUTHOR]

Background: The periodontal ligament (PDL) experiences considerable mechanical stresses between teeth and bone, vital for tissue adaptation, especially in orthodontic tooth movement (OTM). While recent research emphasizes the role of innate lymphoid cells (ILCs) in regulating sterile inflammation, their involvement in periodontal tissues during OTM remains largely unexplored. Methods: In this study, PDL tissues from orthodontic patients (n = 8) were examined using flow cytometry to detect ILC subtypes. Transwell co-culture systems were used to expose PDL cells to mechanical strain, followed by measuring migration and ratios of sorted ILC subtypes. Statistical analyses were conducted using paired Student's t-test, Kruskal-Wallis test, Dunn's posttest and one-way/two-way ANOVA with Tukey's post-test (p= 0.05; **, p= 0.01; ***, p= 0.001). Results: Our findings demonstrate a significant increase in CD127+ CD161+ ILC frequencies in PDL tissues during OTM, indicating ILC involvement in sterile inflammation induced by orthodontic forces. Co-culture assays show directed migration of ILC subsets towards PDL cells and substantial proliferation and expansion of ILCs. Conclusions: This study is the first to comprehensively investigate the role of ILCs in sterile inflammation during OTM, revealing their presence and distribution within PDL tissues' innate immune response in vivo, and exploring their migratory and proliferative behavior in vitro. The results suggest a crosstalk between ILCs and PDL cells, potentially influencing the inflammatory response and tissue remodeling processes associated with OTM. [ABSTRACT FROM AUTHOR]

Background Aim Material and Methods Results Conclusions Tooth avulsion necessitates swift replantation, for which the preservation of periodontal ligament (PDL) cell viability is paramount. Various storage media have been explored, yet a comparison between amniotic fluid (AF) obtained at different gestational stages (amniocentesis and full‐term) and HBSS is lacking.This study aims to evaluate AF (amniocentesis and full‐term) against HBSS in sustaining PDL cell viability and regulating apoptosis at different time points.Periodontal fibroblasts cultured in α‐MEM were treated with 100% AF (amniocentesis), 100% AF (full‐term), and HBSS, incubated for 1, 3, 24, and 48 h at 37°C, and assessed using the MTT assay for viability and AO/EB staining for apoptosis, which was analyzed via fluorescent microscopy after 24 h. Statistical analysis was conducted using one‐way ANOVA, multivariate ANOVA, and post hoc Tukey's multiple comparison tests (p < .05).Amniotic fluid (amniocentesis) exhibited the highest optical density (OD), which implies the highest cell viability across time intervals, followed by AF (full‐term) and HBSS. While HBSS maintained PDL morphology, both AF groups showed altered morphology. No cell death was observed after 24 h.Within the limitations of this study, both AF groups showed the potential to sustain PDL cell viability after 1, 3, 24, and 48 h of storage. However, further investigation is warranted regarding their suitability as storage media. [ABSTRACT FROM AUTHOR]

Periodontitis is a serious form of oral gum inflammation with recession of gingival soft tissue, destruction of the periodontal ligament, and absorption of alveolar bone. Management of periodontal tissue and bone destruction, along with the restoration of functionality and structural integrity, is not possible with conventional clinical therapy alone. Guided bone and tissue regeneration therapy employs an occlusive biodegradable barrier membrane and graft biomaterials to guide the formation of alveolar bone and tissues for periodontal restoration and regeneration. Amongst several grafting approaches, alloplastic grafts/biomaterials, either derived from natural sources, synthesization, or a combination of both, offer a wide variety of resources tailored to multiple needs. Examining several pertinent scientific databases (Web of Science, Scopus, PubMed, MEDLINE, and Cochrane Library) provided the foundation to cover the literature on synthetic graft materials and membranes, devoted to achieving periodontal tissue and bone regeneration. This discussion proceeds by highlighting potential grafting and barrier biomaterials, their characteristics, efficiency, regenerative ability, therapy outcomes, and advancements in periodontal guided regeneration therapy. Marketed and standardized quality products made of grafts and membrane biomaterials have been documented in this work. Conclusively, this paper illustrates the challenges, risk factors, and combination of biomaterials and drug delivery systems with which to reconstruct the hierarchical periodontium. [ABSTRACT FROM AUTHOR]

Background: The present study aimed to assess how a concentrated growth factor (CGF) injection affects the rate of orthodontic tooth movement in rabbits. Methods: This experimental investigation employed a split-mouth configuration. Before orthodontic mesialization of the maxillary first molars, CGF was prepared and administered using submucosal injections on the buccal and palatal sides of the maxillary first molars in one randomly assigned quadrant. The opposite quadrant was used as a control. The study examined four time points:1, 2, 3, and 4 weeks. The measurement of tooth movement was conducted at each follow-up point using a digital caliper. The rabbits were euthanized, and their maxillary segments, specifically the maxillary first molars, were studied histologically to identify any alterations occurring on both the tension and compression sides. Results: Significant tooth movement was observed in the experimental sides versus control sides in the second, third, and fourth week of follow-up periods (p ≤ 0.05). Histologically, on the compression side, the CGF group showed bone resorption and periodontal ligament active reactions from the first week and continued throughout the next three weeks. Also, on the tension side, the CGF group depicted cementoblastic and osteoblastic activities from the first week followed by fibroblastic activities from the second week and all activities continued till the fourth week. Conclusions: CGF has the potential to effectively enhance orthodontic tooth movement without adverse clinical or histological effects. [ABSTRACT FROM AUTHOR]

Background Materials and Methods Results Conclusion The aim of this study was to calculate the stress distribution of fiberglass post associated with resin composite crown restoration and fiberglass posts with zirconia restorations in mature and immature endodontically treated central maxillary incisor under various loading conditions.The study created six different study models in a virtual environment: healthy mature maxillary central teeth, intact immature maxillary central teeth, mature maxillary central teeth with fiberglass post associated with resin composite crown restoration, immature maxillary central teeth with fiberglass post associated with resin composite crown restoration, mature maxillary central teeth with fiberglass posts and zirconia restoration, and immature maxillary central teeth with fiberglass posts and zirconia restoration. Loading conditions simulating mastication, trauma, and bruxism were applied to each of the models at different angles and amounts. The von Mises and the maximum and minimum principal stress values in tooth structures (dentin) and support structures (bone, PDL) and materials were observed using finite element stress analysis.The highest stress values in the tissue and the restoration structure were observed for masticating force and crowns rehabilitated with zirconia restorations. None of the compared loading conditions and restorations showed destructive stress values on periodontal ligament or bone.The mature and immature endodontically treated central maxillary incisors can be better rehabilitated using fiberglass post associated with resin composite crown restoration and may be preferred to zirconia restorations in order to reduce the stresses on the surrounding tissues and teeth. However, further clinical studies are needed to fully explore this topic. [ABSTRACT FROM AUTHOR]

The regenerative treatment of infectious vertical bone defects remains difficult and challenging today. Current clinical treatments are limited in their ability to control bacteria and infection, which is unfavorable for new bone formation and calls for a new type of material with excellent osteogenic and antibacterial properties. Here a multifunctional scaffold is synthesized that mimics natural bone nanostructures by incorporating silver nanowires into a hierarchical, intrafibrillar mineralized collagen matrix (IMC/AgNWs), to achieve the therapeutic goals of inhibiting bacterial activity and promoting infectious alveolar bone augmentation in rats and beagle dogs. An appropriate concentration of 0.5 mg mL−1 AgNWs is selected to balance biocompatibility and antibacterial properties. The achieved IMC/AgNWs exhibit a broad spectrum of antimicrobial properties against Gram‐negative Porphyromonas gingivalis and Gram‐positive Streptococcus mutans. When the IMC/AgNWs are cocultured with periodontal ligament stem cells, it possesses excellent osteoinductive activities under both non‐inflammatory and inflammatory conditions. By constructing a rat mandibular infected periodontal defect model, the IMC/AgNWs achieve a near‐complete healing through the canonical BMP/Smad signaling. Moreover, the IMC/AgNWs enhance vertical bone height and osseointegration in peri‐implantitis in beagle dogs, indicating the clinical translational potential of IMC/AgNWs for infectious vertical bone augmentation. [ABSTRACT FROM AUTHOR]

This research focused on analyzing gene expression changes in the periodontal ligament (PDL) after tooth re-plantation to identify key genes and pathways involved in healing and regeneration. Utilizing a mouse model, mRNA was extracted from the PDL at various intervals post-replantation for RNA sequencing analysis, spanning from 3 to 56 days. The results revealed significant shifts in gene expression, particularly notable on day 28, supported by hierarchical clustering and principal component analysis. Gene ontology (GO) enrichment analysis highlighted an upregulation in olfactory receptor and G protein-coupled receptor signaling pathways at this time point. These findings were validated through reverse transcription-quantitative PCR (RT-qPCR), with immunochemical staining localizing olfactory receptor gene expression to the PDL and surrounding tissues. Moreover, a scratch assay indicated that olfactory receptor genes might facilitate wound healing in human PDL fibroblasts. These results underscore the importance of the 28-day post-transplant phase as a potential "tipping point" in PDL healing and regeneration. In conclusion, this research sheds light on the potential role of olfactory receptor genes in PDL regeneration, providing a foundation for developing new therapeutic approaches in tooth replantation and transplantation, with broader implications for regenerative medicine in oral health. [ABSTRACT FROM AUTHOR]

Stem cells demonstrate differentiation and regulatory functions. In this discussion, we will explore the impacts of cell culture density on stem cell proliferation, adipogenesis, and regulatory abilities. This study aimed to investigate the impact of the initial culture density of human periodontal ligament stem cells (hPDLSCs) on the adipogenic differentiation of autologous cells. Our findings indicate that the proliferation rate of hPDLSCs increased with increasing initial cell density (0.5–8 × 104 cells/cm2). After adipogenic differentiation induced by different initial cell densities of hPDLSC, we found that the mean adipose concentration and the expression levels of lipoprotein lipase (LPL), CCAAT/enhancer binding protein α (CEBPα), and peroxisome proliferator‐activated receptor γ (PPAR‐γ) genes all increased with increasing cell density. To investigate the regulatory role of hPDLSCs in the adipogenic differentiation of other cells, we used secreted exocrine vesicles derived from hPDLSCs cultivated at different initial cell densities of 50 μg/mL to induce the adipogenic differentiation of human bone marrow stromal cells. We also found that the mean adipose concentration and expression of LPL, CEBPα, and PPARγ genes increased with increasing cell density, with an optimal culture density of 8 × 104 cells/cm2. This study provides a foundation for the application of adipogenic differentiation in stem cells. Significance statement: Autologous adipose tissue grafting is widely used for soft tissue reconstruction. However, it is prone to liquefaction and necrosis, which compromise grafting efficacy. Therefore, it is important to explore the roles of stem cells in adipogenic differentiation and regulation. In this study, we found that the human periodontal ligament stem cell (hPDLSC) proliferation rate increased as the initial cell density increased. We also investigated the adipogenic regulatory role of hPDLSCs in human bone marrow stromal cells (hBMSCs). Taken together, the present study demonstrates that cell density not only affects the adipogenic capacity of hPDLSCs themselves but also affects the adipogenic capacity of hBMSCs via secreted exocrine vesicles, which will establish a new theoretical foundation for the clinical application of stem cell adipogenesis. [ABSTRACT FROM AUTHOR]

Electrospinning technology has recently attracted increased attention in the biomedical field, and preparing various cellulose nanofibril membranes for periodontal tissue regeneration has unique advantages. However, the characteristics of using a single material tend to make it challenging to satisfy the requirements for a periodontal barrier film, and the production of composite fibrous membranes frequently impacts the quality of the final fiber membrane due to the influence of miscibility between different materials. In this study, nanofibrous membranes composed of polylactic acid (PLA) and polycaprolactone (PCL) fibers were fabricated using side-by-side electrospinning. Different concentrations of gelatin were added to the fiber membranes to improve their hydrophilic properties. The morphological structure of the different films as well as their composition, wettability and mechanical characteristics were examined. The results show that PCL/PLA dual-fibrous composite membranes with an appropriate amount of gelatin ensures sufficient mechanical strength while obtaining improved hydrophilic properties. The viability of L929 fibroblasts was evaluated using CCK-8 assays, and cell adhesion on the scaffolds was confirmed by scanning electron microscopy and by immunofluorescence assays. The results demonstrated that none of the fibrous membranes were toxic to cells and the addition of gelatin improved cell adhesion to those membranes. Based on our findings, adding 30% gelatin to the membrane may be the most appropriate content for periodontal tissue regeneration, considering the scaffold's mechanical qualities, hydrophilic properties and biocompatibility. In addition, the PCL-gelatin/PLA-gelatin dual-fibrous membranes prepared using side-by-side electrospinning technology have potential applications for tissue engineering. [ABSTRACT FROM AUTHOR]

Various staging scales have been proposed for the assessment of the visibility of the periodontal ligament space of mandibular third molars on dental panoramic radiographs (PANs) for forensic age assessment in living individuals. However, up to now, there has been no systematic comparison between these staging scales available. We directly compared the 2010 staging scale proposed by Olze et al. with the 2017 staging by Lucas et al. and the 2020 staging by Guo et al. in a German study population. We evaluated 233 PANs from 115 females and 118 males aged 20.0 to 40.9 years using three independent examiners, with one examiner conducting two assessments. We examined the correlation between age and stage, as well as the inter- and intra-rater reliabilities. While the point estimates for the correlation coefficient and the reliability measures were lowest for the Guo scale and highest for the Olze scale, confidence intervals showed a large overlap, particularly for the scales of Olze et al. and Lucas et al. The correlation coefficients between stage and age were consistently lower in females than in males across all methods. In summary, we showed that the staging scales of Olze et al. and Lucas et al. were very similar. The Olze method showed higher point estimates across all analyses, and because there are more reference data available for this method, we argue that it should be preferred as the method of choice for further studies in the field. However, Guo method could be considered for instances, in which the inter-radicular periodontal ligament is not evaluable. [ABSTRACT FROM AUTHOR]

In this study, we isolated human periodontal ligament cells (hPDLCs) to find the optimal time of LIPUS stimulation and to explore how LIPUS affects inflammatory and osteogenic responses in hPDLCs in an inflammatory environment. The target molecules of LIPUS were identified by high‐throughput sequencing. RT–qPCR and WB were used to detect how LIPUS affected the expression of related genes in TNFα‐induced inflammation. The expression of ROS and inflammatory factors was detected by flow cytometry. Immunohistochemistry was used to further verify gene expression in rats. hPDLCs were isolated successfully. The optimal LIPUS stimulation condition was 45 mW/cm2 for 30 min and continued for 3 days, and this intensity significantly promoted the osteogenesis and mineralization of hPDLCs. LIPUS significantly inhibited the upregulation of IL‐6 and ROS, increased the percentage of cells in the G2 phase, inhibited cell apoptosis, and inhibited the upregulation of TLR5 expression in an inflammatory environment. LIPUS can effectively restrain the inflammation and oxidative stress response of hPDLCs and promote osteogenesis in an inflammatory environment. LIPUS inhibited the periodontal inflammatory response through TLR5 in hPDLCs and dental pulp. [ABSTRACT FROM AUTHOR]

Objective: DNA methylation as intensively studied epigenetic regulatory mechanism exerts pleiotropic effects on dental‐derived mesenchymal stem cells (DMSCs). DMSCs have self‐renewal and multidifferentiation potential. Here, this review aims at summarizing the research status about application of DMSCs in tissue engineering and clarifying the roles of DNA methylation in influencing the functions of DMSCs, with expectation of paving the way for its in‐depth exploration in tissue engineering. Method: The current research status about influence of DNA methylation in DMSCs was acquired by MEDLINE (through PubMed) and Web of Science using the keywords 'DNA methylation', 'dental‐derived mesenchymal stem cells', 'dental pulp stem cells', 'periodontal ligament stem cells', 'dental follicle stem cells', 'stem cells from the apical papilla', 'stem cells from human exfoliated deciduous teeth', and 'gingival‐derived mesenchymal stem cells'. Results: This review indicates DNA methylation affects DMSCs' differentiation and function through inhibiting or enhancing the expression of specific gene resulted by DNA methylation‐related genes or relevant inhibitors. Conclusion: DNA methylation can influence DMSCs in aspects of osteogenesis, adipogenesis, immunomodulatory function, and so on. Yet, the present studies about DNA methylation in DMSCs commonly focus on dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs). Little has been reported for other DMSCs. [ABSTRACT FROM AUTHOR]

Objectives: Type 2 diabetes (T2DM), a recognized risk factor for periodontitis, is characterized by insulin resistance. However, the molecular mechanisms concerning the role of insulin resistance in linking T2DM and periodontitis remain poorly elucidated due to the absence of an appropriate T2DM cell model. We aimed to explore an appropriate model of T2DM in human periodontal ligament stem cells (hPDLSCs) and uncover the involved mechanisms. Materials and Methods: hPDLSCs were incubated with common reagents for recapitulating insulin resistance state including high glucose (HG) (15, 25, 35, 45 mM), glucosamine (0.8, 8, 18, 28, 38 mM), or palmitic acid (PA; 100, 200, 400, 800 μM), combined with LPS for 48 h. The insulin signaling pathway, inflammation, and pyroptosis were detected by western blots and quantitative real‐time polymerase chain reaction (RT–qPCR). The effects on osteogenesis were evaluated by alkaline phosphatase staining, alizarin red S staining, RT–qPCR, and western blots. Results: HG failed to recapitulate insulin resistance. Glucosamine was sufficient to induce insulin resistance but failed to trigger inflammation. In total, 100 and 200 μM PA exhibited the most proinflammatory, insulin resistance, and pyroptosis induced role, and inhibited the osteogenic differentiation of hPDLSCs. Conclusion: Palmitic acid is a promising candidate for developing T2DM model in hPDLSCs. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the effect of METTL3 knockdown on osteogenic differentiation of human periodontal ligament stem cells (PDLSCs) in the weak inflammation microenvironments, as well as the underlying mechanisms. Materials and Methods: PDLSCs were stimulated by lipopolysaccharide from Escherichia coli (E. coli LPS), followed by quantification of METTL3. METTL3 expression was assessed using RT‐qPCR and Western blot analysis in periodontitis. METTL3 knockdown PDLSCs were stimulated with or without E. coli LPS. The evaluation included proinflammatory cytokines, osteogenic markers, ALP activity, and mineralized nodules. Bioinformatics analysis and Western blot determined the association between METTL3 and the PI3K/Akt pathway. Results: METTL3 was overexpressed in periodontitis. METTL3 knockdown in PDLSCs reduced proinflammatory cytokines, osteogenic markers, ALP activity, and mineralized nodules in both environments. Bioinformatics analysis suggested a link between METTL3 and the PI3K/Akt pathway. METTL3 knockdown inhibited PI3K/Akt signaling pathway activation. Conclusion: METTL3 knockdown might inhibit osteogenesis in PDLSCs through the inactivation of PI3K/Akt signaling pathway. Concomitant findings might shed novel light on the roles and potential mechanisms of METTL3 in the LPS‐stimulated inflammatory microenvironments of PDLSCs. [ABSTRACT FROM AUTHOR]

Objectives: Periodontal ligament stem cells (PDLSCs) are essential for the treatment of bone diseases because of its great potential to differentiate into osteoblasts. Remarkably, increasing long‐non‐coding RNAs (lncRNAs) have been reported to be involved in the osteogenic differentiation of PDLSCs. Maternally expressed 8, small nucleolar RNA host gene (MEG8) is implicated in multiple diseases. This study intended to unearth the potential role of MEG8 and unveil the mechanism in PDLSCs undergoing osteoblastic differentiation. Materials and Methods: MEG8 expression was measured by quantitative real‐time PCR (RT‐qPCR) during osteogenic differentiation of PDLSCs into bone cells. Functional assays were used to uncover the biological function of MEG8. Besides, RNA pulldown, RNA‐binding protein immunoprecipitation (RIP), and luciferase reporter assays were used to explore the molecular mechanism of MEG8. Results: MEG8 was apparently overexpressed in osteogenically differentiated PDLSCs. Moreover, MEG8 deficiency suppressed the osteoblastic differentiation of PDLSCs. Furthermore, MEG8 modulated the expression of transcription factor 4 (TCF4) by scavenging microRNA‐495‐3p (miR‐495‐3p) and microRNA‐485‐3p (miR‐485‐3p) through the competing endogenous RNA (ceRNA) mechanism, further stimulating the Wnt/β‐catenin pathway. Conclusion: MEG8 stimulates the capacity of PDLSCs for osteogenic differentiation through a ceRNA mode. [ABSTRACT FROM AUTHOR]

Objective: Periodontitis is a type of prevalent chronic inflammatory disorder resulting in a failure in the function of tissues supporting the tooth, like gingiva, alveolar bone, and periodontal ligament. Although antibiotic therapy is a common therapy for periodontitis cases, this approach can cause some adverse effects in these patients. Thus, finding an effective curative option with low side effects is still a puzzle. Materials and Methods: This narrative review was conducted on the effects of herbal and nano-based herbal medicine against periodontitis by searching different databases such as Google Scholar, PubMed, Scopus, Web of Science, Science Direct, and Scientific Information Databases. Results: According to published studies, some popular herbal formulations, such as Aloe vera, curcumin, Melaleuca alternifolia, and Scutellaria baicalensis Georgi, can be effective in periodontitis treatment. However, these herbal products may be accompanied by some pharmacological limitations, such as poor bioavailability, instability, and weak water solubility. On the other hand, harnessing nano-based herbal formulations can elevate the bioavailability, diminish toxicity, and omit repeated administration of drugs. Conclusion: Herbal and nano-based herbal products can create a good chance to treat periodontitis efficiently. [ABSTRACT FROM AUTHOR]

Background: Oral inflammation is among the most prevalent oral pathologies with systemic health implications, necessitating safe and effective treatments. Given curcumin's documented anti‐inflammatory and antioxidant properties, this study focuses on the potential of a curcumin‐based oral gel in safely managing oral inflammatory conditions. Methods: This in vitro study utilized four human cell lines: oral keratinocytes (HOKs), immortalized oral keratinocytes (OKF6), periodontal ligament fibroblasts (HPdLF), and dysplastic oral keratinocytes (DOKs). The cells were treated with Lipopolysaccharides (LPS) and curcumin‐based oral gel to simulate inflammatory conditions. A panel of cellular assays were performed along with antimicrobial efficacy tests targeting Candida albicans, Streptococcus mutans, and Porphyromonas gingivalis. Results: LPS significantly reduced proliferation and wound healing capacities of HOKs, OKF6, and HPdLF, but not DOKs. Treatment with curcumin‐based oral gel mitigated inflammatory responses in HOKs and HPdLF by enhancing proliferation, colony formation, and wound healing, along with reducing apoptosis. However, its impact on OKF6 and DOKs was limited in some assays. Curcumin treatment did not affect the invasive capabilities of any cell line but did modulate cell adhesion in a cell line‐specific manner. The curcumin‐based oral gel showed significant antimicrobial efficacy against C. albicans and S. mutans, but was ineffective against P. gingivalis. Conclusion: This study demonstrates the potential of the curcumin‐based oral gel as a safe and effective alternative to conventional antimicrobial treatments for managing cases of oral inflammation. This was achieved by modulating cellular responses under simulated inflammatory conditions. Future clinical‐based studies are recommended to exploit curcumin's therapeutic benefits in oral healthcare. [ABSTRACT FROM AUTHOR]

The study aims to evaluate the stresses and the deformations generated at the periodontal level by two mandibular advancement devices (MADs) using finite element analysis. A three-dimensional digital model of the skull of a 29-year-old patient was created using a CBCT. The 3D models of two MADs (Somnodent FlexTM and Somnodent AvantTM) were reconstructed from scanning prototypes based on the patient's anatomy. The overall geometry was imported into software for the finite element study. A force of 11.18 N representing an advancement of 9.5 mm was applied to the devices. A finite element analysis wfas subsequently performed. Somnodent FlexTM generates a peak of 3.27 kPa on periodontal ligaments and 287 kPa on teeth. For Somnodent AvantTM the maximum stress is 4.53 kPa on periodontal ligaments and 467 kPa on teeth. Different activation mechanisms of the devices generate stresses of different entities. [ABSTRACT FROM AUTHOR]