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Background: Diabetes, among multiple systemic harmful health issues, also may deteriorate normal regenerative and reparative functions of periodontium. The aim of this research was to study the role of periodontal ligament in tissue remodeling under the orthodontic appliance stimulation in two rat experimental models (healthy Wistar rats and Goto-Kakizaki, rodent model of non-obese type 2 diabetes). Materials and methods: It was defined four groups of rats: Wistar (n = 8) and Goto-Kakizaki (n = 8) control groups without orthodontic appliances, and Wistar (n = 16) and Goto-Kakizaki (n = 16) appliance groups with orthodontic appliances. After 42 days, rats were sacrificed and histopathology descriptive analysis about periodontal ligament and adjacent structures was performed as well as cellularity of periodontal ligament and Kappa curvature of tooth roots were measured. Results: Goto-Kakizaki control rats showed statistically significantly higher cellularity in comparison with Wistar control rats (p

Macrophages (MQ) are major constituents of chronically inflamed periapical tissues in apical periodontitis. This study aimed to investigate the immunomodulatory effect of engineered bioactive chitosan-based nanoparticles (CSnp) antibiofilm medication on MQ cocultured with periodontal ligament fibroblasts (PdLF). Cells viability, spreading, PdLF migration, and intracellular CSnp uptake were characterized. Tandem Mass Tag-based proteomics was applied to analyze MQ global protein expression profiles after interaction with Enterococcus faecalis biofilm, CSnp-treated biofilm, and CSnp. Secreted inflammatory mediators were analyzed. Following bioinformatics analyses, candidate proteins were validated via targeted proteomics. CSnp maintained cells viability, increased MQ spreading, and PdLF migration (p 1.5-folds, p 1.5-folds, p, Graphical abstract This study elucidated the immunomodulatory effect of engineered bioactive chitosan-based nanoparticles (CSnp) as antibiofilm medication on macrophage (MQ) co-cultured with periodontal ligament fibroblasts (PdLF) via proteomic and cytokine analyses. CSnp were internalized via different endocytic pathways. Cells interaction with CSnp resulted in increased MQ spreading and PdLF migration. MQ inflammatory response to CSnp-treated biofilm was compared to untreated biofilm. Quantitative proteomics of MQ was done using tandem mass tag (TMT)-mass spectrometry (MS). Bioinformatics analysis of global proteomic data was followed by validation of candidate proteins via parallel reaction monitoring (PRM)-targeted MS. CSnp upregulated proteins having immunoregulatory and antioxidant activities. MQ stimulated with CSnp-treated biofilm produced higher anti-inflammatory but lower pro-inflammatory mediators. Engineered CSnp has the potential to regulate biofilm-mediated inflammation to promote periapical healing in the treatment of apical periodontitis (Schematic created with BioRender.com).Image 1., Highlights • CSnp internalized via macropinocytosis, clathrin-mediated endocytosis, and phagocytosis. • Enterococcus faecalis biofilm altered macrophage proteomic profile. • Macrophage proteome upon CSnp-treated biofilm interaction was distinct from biofilm. • CSnp upregulated proteins with immunoregulatory and antioxidant activities. • CSnp reduced proinflammatory but increased anti-inflammatory mediators.

Engineering a complete, physiologically functional, periodontal complex structure remains a great clinical challenge due to the highly hierarchical architecture of the periodontium and coordinated regulation of multiple growth factors required to induce stem cell multilineage differentiation. Using biomimetic self-assembly and microstamping techniques, we construct a hierarchical bilayer architecture consisting of intrafibrillarly mineralized collagen resembling bone and cementum, and unmineralized parallel-aligned fibrils mimicking periodontal ligament. The prepared biphasic scaffold possesses unique micro/nano structure, differential mechanical properties, and growth factor-rich microenvironment between the two phases, realizing a perfect simulation of natural periodontal hard/soft tissue interface. The interconnected porous hard compartment with a Young's modulus of 1409.00 ± 160.83 MPa could induce cross-arrangement and osteogenic differentiation of stem cells in vitro, whereas the micropatterned soft compartment with a Young's modulus of 42.62 ± 4.58 MPa containing abundant endogenous growth factors, could guide parallel arrangement and fibrogenic differentiation of stem cells in vitro. After implantation in critical-sized complete periodontal tissue defect, the biomimetic bilayer architecture potently reconstructs native periodontium with the insertion of periodontal ligament fibers into newly formed cementum and alveolar bone by recruiting host mesenchymal stem cells and activating the transforming growth factor beta 1/Smad3 signaling pathway. Taken together, integration of self-assembly and microstamping strategies could successfully fabricate a hierarchical bilayer architecture, which exhibits great potential for recruiting and regulating host stem cells to promote synergistic regeneration of hard/soft tissues., Graphical abstract Image 1, Highlights •A CGF/IMC biphasic scaffold is made by a self-assembly integrated microstamping strategy. •CGF/IMC mimics periodontium in micro/nano structure, mechanics and growth factor environment. •CGF/IMC bidirectionally regulates osteogenic/fibrogenic differentiation of stem cells. •CGF/IMC achieves complete periodontal regeneration by recruiting host stem cells.

Osteosarcoma is the most common primary malignancy of the jaws and is treated by radical surgical resection. Early detection is crucial since removing the lesion with clean margins contributes most to outcome. We present three cases of osteosarcoma occurring in the interradicular region of the mandible, two of which were thought to represent non-malignant processes upon initial presentation. All three demonstrated early but significant clinical and radiographic features indicative of the malignant disease process. Radiographically, all of these cases had in common unilateral periodontal ligament (PDL) space widening, displacement of teeth, and growth of the crestal bone. Clinically, all three cases presented with a painless intraoral swelling. Case 1: A 20 year old African American male presented with a swelling and loose teeth of 1.5 months duration. Histopathological diagnosis of osteoblastic osteosarcoma, high grade was made. Case 2: A 75 year old Caucasian male presented with a 2 × 2 cm expansile lesion of two months duration. Histopathological diagnosis of chondroblastic osteosarcoma was made. Case 3: A 63 year old Caucasian female presented with a 5-6 mm lesion for at least 1 month duration. Histopathological diagnosis of chondroblastic osteosarcoma was made. All three cases were treated with wide surgical resection.

Periodontitis is a common disorder affecting >40% of adults in the United States. Globally, the severe form of the disease has a prevalence of 11%. In advanced cases, periodontitis leads to tooth loss and reduced quality of life. The aetiology of periodontitis is multifactorial. Subgingival dental biofilm elicits a host inflammatory and immune response, ultimately leading to irreversible destruction of the periodontium (i.e. alveolar bone and periodontal ligament) in a susceptible host. In order to successfully manage periodontitis, dental professionals must understand the pathogenesis, primary aetiology, risk factors, contributing factors and treatment protocols. Careful diagnosis, elimination of the causes and reduction of modifiable risk factors are paramount for successful prevention and treatment of periodontitis. Initial non-surgical periodontal therapy primarily consists of home care review and scaling and root planing. For residual sites with active periodontitis at periodontal re-evaluation, a contemporary regenerative or traditional resective surgical therapy can be utilised. Thereafter, periodontal maintenance therapy at a regular interval and long-term follow-ups are also crucial to the success of the treatment and long-term retention of teeth. The aim of this review is to provide current concepts of diagnosis, prevention and treatment of periodontitis. Both clinical and biological rationales will be discussed.

Introduction The purpose of this prospective study was to determine the effect of a combination of nitrous oxide/oxygen and 1 set of supplemental intraligamentary/periodontal ligament (PDL) injections followed by a second set of PDL injections on anesthetic success in patients with symptomatic irreversible pulpitis (SIP). Methods Ninety-four patients with a mandibular posterior tooth diagnosed with SIP received nitrous oxide/oxygen and an inferior alveolar nerve block (IANB) with 2% lidocaine with 1:100,000 epinephrine. Patients rated the pain of PDL injections and endodontic access on a visual analog scale. If moderate to severe pain was felt during treatment, the operator administered 1 set of supplemental PDL injections with 4% articaine with 1:100,000 epinephrine. If moderate to severe pain was felt again during treatment, the operator administered a second set of supplemental PDL injections. Anesthetic success was defined as having no to mild pain during endodontic treatment. Results The success of the IANB with nitrous oxide was 44% (95% confidence interval [CI], 34%–54%). The overall anesthetic success rate (IANB with PDL injections) was increased from 69% (95% CI, 60%–78%) with 1 set of PDL injections to 80% (95% CI, 72%–88%) with a second set of PDL injections. Conclusions Although the second set of PDL injections increased anesthetic success, it was not sufficient to ensure complete pulpal anesthesia.

The functional interplay between cementum of the root and alveolar bone of the socket is tuned by a uniquely positioned 70-80 µm wide fibrous and lubricious ligament in a dentoalveolar joint (DAJ). In this study, structural and biomechanical properties of the DAJ, periodontal ligament space (PDL-space also known as the joint space), alveolar bone of the socket, and cementum of the tooth root that govern the biomechanics of a lipopolysaccharide (LPS)-affected DAJ were mapped both in space and time.The hemi-maxillae from 20 rats (4 control at 6 weeks of age, 4 control and 4 LPS-affected at 12 weeks of age, 4 control and 4 LPS-affected at 16 weeks of age) were investigated using a hybrid technique; micro-X-ray computed tomography (5 µm resolution) in combination with biomechanical testing in situ. Temporal variations in bone and cementum volume fractions were evaluated. Trends in mineral apposition rates (MAR) in additional six Sprague Dawley rats (3 controls, 3 LPS-affected) were revealed by transforming spatial fluorochrome signals to functional growth rates (linearity factor - RW) of bone, dentin, and cementum using a fast Fourier transform on fluorochrome signals from 100-µm hemi-maxillae sections.An overall change in LPS-affected DAJ biomechanics (a 2.5-4.5X increase in tooth displacement and 2X tooth rotation at 6 weeks, no increase in displacement and a 7X increase in rotation at 12 weeks; 27% increase in bone effective strain at 6 weeks and 11% at 12 weeks relative to control) was associated with structural changes in the coronal regions of the DAJ (15% increase in PDL-space from 0 to 6 weeks but only 5% from 6 to 12 weeks compared to control). A significant increase (p0.05) in PDL-space between ligated and age-matched control was observed. The bone fraction of ligated at 12 weeks was significantly lower than its age-matched control, and no significant differences (p 0.05) between groups were observed at 6 weeks. Cementum in the apical regions grew faster but nonlinearly (11% and 20% increase in cementum fraction (CF) at 6 and 12 weeks) compared to control. Alveolar bone revealed site-specific nonlinear growth with an overall increase in MAR (108.5 µm/week to 126.7 µm/week after LPS treatment) compared to dentin (28.3 µm/week in control vs. 26.1 µm/week in LPS-affected) and cementum (126.5 µm/week in control vs. 119.9 µm/week in LPS-affected). A significant increase in CF (p 0.05) in ligated specimens was observed at 6 weeks of age.Anatomy-specific responses of cementum and bone to the mechano-chemo stimuli, and their collective temporal contribution to observed changes in PDL-space were perpetuated by altered tooth movement. Data highlight the "resilience" of DAJ function through the predominance of nonlinear growth response of cementum, changes in PDL-space, and bone architecture. Despite the significant differences in bone and cementum architectures, data provided insights into the reactionary effects of cementum as a built-in compensatory mechanism to reestablish functional competence of the DAJ. The spatial shifts in architectures of alveolar bone and cementum, and consequently ligament space, highlight adaptations farther away from the site of insult, which also is another novel insight from this study. These adaptations when correlated within the context of joint function (biomechanics) illustrate that they are indeed necessary to sustain DAJ function albeit being pathological.

The periodontal ligament (PDL) is exposed to constant mechanical forces potentiated by orthodontic tooth movement (OTM). The aim of our study was to investigate the involvement of chaperone-assisted selective autophagy (CASA) in mechanosensing and cellular adaption to forces in the PDL.Human PDL cells were loaded with 2.5, 5, and 10% of static mechanical strain for 24 h in vitro. Untreated cells served as controls. Gene expression of HSPA8, HSPB8, BAG3, STUB1, SYNPO2 was investigated via RT-qPCR (Quantitative reverse transcription PCR). Western blot evidenced protein expression of these molecules and of Filamin A. In vivo analyses of CASA were performed via immunohistochemistry on teeth with and without OTM.CASA machinery genes were inherently expressed in PDL cells and exhibited transcriptional induction upon mechanical strain. Protein analyses underlined these findings, even though modulation upon force exertion also demonstrated a decrease for some molecules and loading strengths. In vivo results evidenced again the uniform upregulation of HSPA8, HSPB8, BAG3, STUB1, SYNPO2 and Filamin A in teeth with OTM compared to controls. Experiments generally evidenced a pronounced variability in the expression between donors both on the gene and protein level.Our study is the first to identify both the expression and functional relevance of CASA in the PDL. The data reflect its probable central role in adequate adaption to forces exerted by OTM and in mechanical stress protection of cells. Deeper knowledge of the CASA pathway will allow better assessment of predisposing factors regarding side effects during mechanical force application that can be used in orthodontic practice.HINTERGRUND: Das Parodontalligament (PDL) ist unter physiologischen Bedingungen permanent mechanischen Kräften ausgesetzt, welche durch kieferorthopädische Zahnbewegung (OTM) nochmals potenziert werden. Ziel dieser Studie war die Untersuchung der Rolle von Chaperon-assistierter selektiver Autophagie (CASA) bei der Mechanosensation und der kraftinduzierten Stressadaptation von PDL-Zellen.Humane PDL-Zellen wurden in vitro einer statischen Dehnung von 2,5, 5 und 10 % für 24 h ausgesetzt. Nichtstimulierte Zellen dienten als Kontrolle. Analysiert wurde die Genexpression der CASA-Moleküle HSPA8, HSPB8, BAG3, STUB1, SYNPO2 via RT-qPCR sowie die Proteinexpression dieser Moleküle und diejenige von Filamin A mittels Western-Blot. In-vivo-Analysen der CASA wurden mit immunohistochemischen Verfahren an Zähnen mit sowie ohne OTM durchgeführt.Alle untersuchten CASA-Moleküle wurden ubiquitär von PDL-Zellen exprimiert und unter mechanischer Belastung hochreguliert. Die Proteinanalysen bestätigten diese Ergebnisse, obwohl eine Modulation bei der Kraftaufwendung für einige Moleküle und Belastungsintensitäten auch einen Rückgang zeigte. Die in vivo Ergebnisse waren deckungsgleich mit den Genanalysen und zeigten eine einheitliche Hochregulation von HSPA8, HSPB8, BAG3, STUB1, SYNPO2 und Filamin A bei Zähnen mit OTM verglichen mit unbehandelten Kontrollzähnen. Die Experimente zeigten im Allgemeinen eine ausgeprägte Variabilität in der Expression zwischen den Spendern sowohl auf Gen- als auch auf Proteinebene.Unsere Studie ist die erste wissenschaftliche Arbeit, die sowohl die CASA-Moleküle als auch deren funktionelle Relevanz im PDL nachweist. Die Daten zeigen, dass CASA höchstwahrscheinlich eine zentrale Rolle spielt für die adäquate Adaptation an OTM-induzierte Krafteinwirkungen und als protektiver Faktor für Zellen bei mechanischem Stress. Genauere Kenntnisse des CASA-Signalweges werden es ermöglichen, Prädispositionsfaktoren für unerwünschte Wirkungen beim Einsatz mechanischer Belastung künftig besser einzuschätzen.

Mesenchymal stem cells (MSCs) are extensively used in tissue regenerative procedures. One source of MSCs is the periodontal ligament (PDL) of teeth. Isolation of MSCs from extracted teeth is reasonably simple, being less invasive and presenting fewer ethical concerns than does the harvesting of MSC’s from other sites. The objectives of this study were to isolate and characterize the PDL stem cells (PDLSC) from healthy adults’ extracted teeth and then to characterize them by comparing them with bone-marrow derived MSCs (BMMSC). Methods The PDL tissue was scraped from the roots of freshly extracted teeth to enzymatically digest using collagenase. The cells were sub-cultured. Flow-cytometric analysis for the MSC surface-markers CD105, CD73, CD166, CD90, CD34, CD45 and HLA-DR was performed. To confirm the phenotype, total RNA was extracted to synthesize cDNA and which was then subjected to RT-PCR. The gene-expression for Oct4A, Sox2, NANOG and GAPDH was determined by gel-electrophoresis. To assess their multilineage potential, cells were cultured with osteogenic, chondrogenic and adipogenic medium and then stained by Alizarin-red, Alcian-blue and Oil-Red-O respectively. MSCs from the bone-marrow were processed similarly to serve as controls. Results The cells isolated from extracted teeth expanded successfully. On flow-cytometric analysis, the cells were positive for CD73, CD90, CD105, CD166 and negative for CD34, CD45 and HLA-DR. The PDLSCs expressed Oct4A, Sox2, and NANOG mRNA with GAPDH expression. Cells cultured in the osteogenic, chondrogenic and adipogenic media stained positive for Alizarin-red, Alcian-blue and Oil- Red-O respectively. The surface marker expression and the trilineage differentiation characteristics were comparable to those of the BMMSCs. Conclusions The periodontal ligament tissue of extracted teeth is a potential source of therapeutically useful MSCs. Harvesting them is not invasive and are a promising source of MSC as the PDLSCs showed characteristics similar to those of the highly regarded MSC’s derived from bone-marrow.

This study aimed to evaluate the regenerative capacity of a newly-developed polycaprolactone (PCL)-based nanofibrous composite scaffold either alone or in combination with adipose-derived mesenchymal stem cells (ADSCs) as a treatment modality for class II furcation defects. After ADSCs isolation and scaffold characterization, the mandibular premolars of adult male mongrel dogs were selected and randomly assigned into three equal groups. In group I, class II furcation defects were surgically induced to the inter-radicular bone. While class II furcation defects of group II were induced as in group I. In addition, the defects were filled with the prefabricated scaffold. Moreover, class II furcation defects of group III were induced as in group II and instead the defects were filled with the prefabricated scaffold seeded with ADSCs. The dogs were sacrificed at 30 days or at 60 days. Periodontal wound healing/regeneration was evaluated by radiological examination using cone beam computed tomography and histologically using ordinary, histochemical, and immunohistochemical staining. In the two examination periods, group II defects compared to group I, and group III compared to the other groups showed a decrease in defect dimensions radiographically. Histologically, histochemically, and immunohistochemically, they significantly demonstrated better periodontal wound healing/regeneration, predominant collagen type I of newly formed bone and periodontal ligament with a significant increase in the immunoreactivity of vascular endothelial growth factor and osteopontin. The newly fabricated nanofibrous scaffold has enhanced periodontal wound healing/regeneration of class II furcation defects with further enhancement achieved when ADSCs seeded onto the scaffold before implantation. The implementation of our newly-developed PCL-based nanofibrous composite scaffolds in class II furcation defect either alone or in conjunction with ADSCs can be considered as a suitable treatment modality to allow periodontal tissues regeneration.

Due to the complexity of the structure of the tooth periodontium, regeneration of the full tooth attachment is not a trivial task. There is also a gap in models that can represent human tooth attachment in vitro and in vivo. The aim of this study was to develop a bilayered in vitro construct that simulated the tooth periodontal ligament and attached alveolar bone, for the purpose of tissue regeneration and investigation of physiological and orthodontic loading. Two types of materials were used to develop this construct: sol-gel 60S10Mg derived scaffold, representing the hard tissue component of the periodontium, and commercially available Geistlich Bio-Gide® collagen membrane, representing the soft tissue component of the tooth attachment. Each scaffold was dynamically seeded with human periodontal ligament cells (HPDLCs). Scaffolds were either cultured separately, or combined in a bilayered construct, for 2 weeks. Characterisation of the individual scaffolds and the bilayered constructs included biological characterisation (cell viability, scanning electron microscopy to confirm cell attachment, gene expression of periodontium regeneration markers), and mechanical characterisation of scaffolds and constructs. HPDLCs enjoyed a biocompatible 3-dimensional environment within the bilayered construct components. There was no drop in cellular gene expression in the bilayered construct, compared to the separate scaffolds.

Chronic periodontal is a very common infection that instigates the destruction of oral tissue, and for its treatment, it is necessary to minimize the infection and the defects regeneration. Periodontium consists of four types of tissues: (a) cementum, (b) periodontal ligament, (c) gingiva, and 4) alveolar bone. In separated cavities, regenerative process also allows various cell proliferations. Guided tissue regeneration (GTR) is a potential procedure that favors periodontal regrowth; however, some limitations (such as ineffective hemostatic property, poor mechanical property, and improper biodegradation) are also associated with it. This review mainly emphasizes on the following areas: (a) a summarized overview of the periodontium and its immunological situations, (b) recently utilized treatments for regeneration of distinctive periodontal tissues; (c) an overview of GTR membranes available commercially, and the latest developments on the characterization and processing of GTR membrane material; and 4) the function of the different non-polymeric/polymeric materials, which are acting as drug carriers, antibacterial agents, nanoparticles, and periodontal barrier membranes to prevent periodontal inflammation and to improve the strength of the GTR membrane.

Periodontal disease is a chronic inflammatory, multifactorial condition, that, in the absence of an early and adequate treatment, may lead to a progressive damaging of the alveolar tissues that support the teeth (periodontal ligament, cement and alveolar bone) followed by teeth mobility and, subsequently, their loss. Periodontal disease is one of the most common inflammatory disease affecting adult individuals all over the world, being considered a real worldwide pandemic. This disease may influence the progression of certain systemic diseases: diabetes mellitus, cardiovascular diseases, ischemic cardiomyopathy, myocardial infarction, stroke, neurodegenerative diseases, chronic kidney diseases, cancer, etc. The association between smoking and periodontal disease was described in numerous clinical and epidemiological studies, suggesting that products derived from tobacco burning may change the clinical aspects and the disease progression. The present study analyzed microscopically and immunohistochemically 58 periodontal fragments, from 50 patients, chronic smokers, clinically diagnosed with severe periodontitis. There were highlighted major changes in the gingival epithelium (epithelium thickening, acanthosis, intraepithelial edema, infiltrates of neutrophils or lymphocytes, epithelial necrosis), in the periodontal conjunctive tissue (more or less intense inflammatory infiltrates, microhemorrhages, vascular congestion, intense immunohistochemical expression for some matrix metalloproteinases). The periodontal changes may be the expression of both toxic factors present in tobacco smoke and due to the changes caused by tobacco in the microbial flora of the oral cavity.

This study aimed to investigate the optimal activation of plastic aligner for the canine distal movement by combining the stress and strain of periodontal ligament. Computer-aided design models of the upper canine, periodontal ligament, alveolar bone, and plastic aligner were constructed. The stresses and strains of periodontal ligament were acquired by fitting plastic aligner on the canine, which will cause the canine distal-direction movement. The activation of plastic aligner was set into 12 groups, including 0.050, 0.100, 0.125, 0.150, 0.175, 0.200, 0.225, 0.250, 0.275, 0.300, 0.350, and 0.400 mm. Assuming the volume-averaged hydrostatic stress (VAHS) ranging from 4.7 to 16 kPa to be the optimal stress, and an average strain no less than 0.3 to be the optimal strain. The optimal activation of plastic aligner was acquired based on the optimal stress and average strain. As the activation increased, the stress and strain of periodontal ligament increased visibly. The degree of activation of plastic aligner was nonlinearly and positively related to VAHS and average strain. According to the fitted curves, the activation corresponding to the optimal stress was 0.07–0.24 mm and the activation was not less than 0.21 mm based on the optimal strain. The optimal activation of plastic aligner for the canine distal movement was 0.21–0.24 mm in this study. The degree of activation affects the force system of orthodontic tooth movement, and it should be taken into consideration to obtain healthy and efficient tooth movement. The activation with 0.21–0.24 mm seems optimal for orthodontic tooth movement in the plastic aligner system in this study.

Introduction: Regenerative therapies for periodontium aims to regenerate damaged periodontal tissue. Stem cell-based regenerative therapy may represent an effective therapeutic tool for periodontal regeneration. Periodontal ligament stem cells (PDLSCs) are a type of somatic stem cell that shows the potential to differentiate into several cell types and perform strong self-renewal. Therefore, PDLSCs are considered as a highly promising stem cell population for regenerative therapy in the periodontium and need further knowledge regarding the potential of using PDLSCs as a regenerative periodontium therapy. Literature Review: The periodontal ligament is a marker for stem cells, which is STRO-1. The STRO-1 marker is a colony-forming osteogenic precursor that can be isolated from bone marrow. The STRO1 marker has the potential to be a phenotype of adipocytes, chondrocytes, and osteocytes. Markers of expression of STRO-1 from the surface of the periodontal ligament show that periodontal ligament cells have osteogenic precursors that can differentiate into osteoblasts. The potential multilineage differentiation of PDLSC including the adipogenic, chondrogenic, and osteogenic potential of PDLSC makes a promising cell source for cell-based regenerative periodontal therapy. Conclusion: The ability of PDLSCs in self-renewal, multipotency, and stem cell immunomodulators, provides satisfactory results in the treatment of periodontal defects.

Background Guinea pigs with dental disease usually present with nonspecific signs such as reduced food intake, difficulty eating and poor general condition. It is assumed that deficient dental attrition is the cause for overlong teeth. Giant teeth, or Macrodonts, have been mentioned as an occasionally occurring pathology. Methods Guinea pigs with clinically and radiologically confirmed dental disease presented between 2011 and 2014 and with complete sets of radiographs of the skull (laterolateral, dorsoventral, oblique and isolated views of the mandible and maxilla) were included in this retrospective study (n = 131). Every tooth was radiologically assessed and documented as changed, if an alteration in tooth width, tooth structure, periodontal ligament space, alveolar bone lamina dura and, in the incisors, pulp cavity was present. Special focus was placed on macrodonts and their additional alterations besides increase in width. Results The majority (89% = 116/131) of all guinea pigs had at least one macrodont; more than half (58% = 246/422) of all abnormal teeth were macrodonts. In total, 246 teeth (54 incisors, 192 cheek teeth) were diagnosed as macrodonts by means of radiography based on the presence of tooth expansion. Mandibular incisors were much more often affected by macrodontia (87%, 47/54). Furthermore, 91% (175/192) of cheek teeth macrodonts were found in the last two tooth positions. In the present study 97% of all macrodonts (238/246) showed both expansion and structural loss. Alterations to the periodontal ligament space were found in 76% (118/246) of macrodonts. The lamina dura of alveolar bone was changed in 46% (113/246) of cases. Abnormalities of the pulp cavity were present in 80% (43/54) of incisor macrodonts. Conclusion and clinical relevance In conclusion, macrodonts occur much more often than previously documented and present a common diagnostic finding in guinea pigs with dental disease. Macrodontia is radiologically characterised by expansion of the tooth and structural loss.

The periodontium is an integrated, functional unit of multiple tissues surrounding and supporting the tooth, including but not limited to cementum (CM), periodontal ligament (PDL) and alveolar bone (AB). Periodontal tissues can be destructed by chronic periodontal disease, which can lead to tooth loss. In support of the treatment for periodontally diseased tooth, various biomaterials have been applied starting as a contact inhibition membrane in the guided tissue regeneration (GTR) that is the current gold standard in dental clinic. Recently, various biomaterials have been prepared in a form of tissue engineering scaffold to facilitate the regeneration of damaged periodontal tissues. From a physical substrate to support healing of a single type of periodontal tissue to multi-phase/bioactive scaffold system to guide an integrated regeneration of periodontium, technologies for scaffold fabrication have emerged in last years. This review covers the recent advancements in development of scaffolds designed for periodontal tissue regeneration and their efficacy tested in vitro and in vivo. Pros and Cons of different biomaterials and design parameters implemented for periodontal tissue regeneration are also discussed, including future perspectives., Graphical abstract Image 1, Highlights • Periodontal diseases are a major cause of tooth loss and the current treatment suffers from limitations. • Biomaterial scaffold-guided regeneration of periodontal tissues have recently emerged. • This review addresses the recent advance in bioactive scaffold for integrated regeneration of multiple periodontal tissues. • The outstanding limitations and future perspectives are also discussed.

Achieving primary stability in dental implants is crucial factor for accomplishing successful osteointegration with bone. Micro-motions higher than the threshold of 50 to 100 ?m can lead to formation of fibrous tissue at the bone-to-implant interface. Therefore, osteointegration may be vitiated due to insufficient primary stability. Osseointegration is defined as a direct and functional connection between the implant biomaterial and the surrounding bone tissue. Osseointegration development requires an initial rigid implant fixation into the bone at the time of surgery and a secondary stage of new bone apposition directly onto the implant surface. Dental implants function to transfer the load to the surrounding biological tissues. Due to the absence of a periodontal ligament, its firm anchorage to bone, various forces acting on it and the presence of prosthetic components, they share a complex biomechanical relationship. The longevity of these osseointegrated implants depend on optimizing these complex interactions. Hence, the knowledge of forces acting on implant, design considerations of implant and bone mechanics is essential to fabricate an optimized implant supported prosthesis. Keywords: Dental Implant, Biomechanics, Bone­implant interface, Osseointegration, stability

Periodontitis is an inflammatory disease resulting from subgingival microorganisms. Human periodontal ligament stem cells (hPDLSCs) can be applied in periodontal tissue regeneration. This study investigated the effect of hPDLSC-derived extracellular vesicles (EVs) on periodontitis. hPDLSC-derived EVs were isolated and identified. The murine model of periodontitis was established by ligation, and the cell model of periodontitis was established by treatment of macrophages with lipopolysaccharide (LPS). The effects of EVs on macrophage pyroptosis and periodontal inflammatory injury were measured by the means of HE staining, detection of LDH content, CCK-8 assay, Calcein-AM/PI staining, ELISA, Western blot, as well as measurement of caspase-1, SOD, and MDA. miR-590-3p expression was detected using RT-qPCR. miR-590-3p expression was then intervened to validate the effect of miR-590-3p on macrophage pyroptosis. The binding relationship between miR-590-3p and TLR4 was verified using dual-luciferase assay. Functional rescue experiment was performed to validate the role of TLR4 in macrophage pyroptosis. The results showed that inflammatory levels and macrophage pyroptosis were enhanced in the in vivo and in vitro models of periodontitis, evidenced by the increased NLRP3, GSDMD-N, caspase-1, IL-1β, IL-18, TNF-α, and MDA and decreased IL-10 and SOD. EVs alleviated periodontal inflammatory injury and macrophage pyroptosis. Physiologically, EVs carried miR-590-3p into macrophages to upregulate miR-590-3p expression and thereby suppress TLR4 transcription. miR-590-3p silencing or TLR4 overexpression reduced the inhibitory effect of EVs on macrophage pyroptosis. Collectively, EVs carried miR-590-3p into macrophages to subsequently inhibit TLR4 transcription, thereby reducing macrophage pyroptosis and alleviating periodontal inflammatory injury.

This study aimed to evaluate the effect of micro-osteoperforations (MOPs) on the gene expression profile of the periodontal ligament (PDL) of orthodontically moved teeth. Fifteen participants were randomly assigned into two groups: tooth movement only (Tr1, n = 7) and tooth movement supplemented with MOPs (Tr2, n = 8). In each subject, orthodontic tooth movement (OTM) was performed on premolar in one side, while no force was applied on contralateral premolar (Unt, n = 15). Seven days after loading, premolars were extracted for orthodontic reasons. RNA extraction from PDL and subsequent RNA-sequencing were performed. False discovery rates (Padj

Increased levels of heat shock proteins after several types of stress play a central role in cellular homeostasis allowing for continued cell survival. This study was aimed at quantitatively analysing the expression pattern of major damage associated molecular patterns (DAMPs) - HSP70, and the amount of nuclear damage incident in periodontal ligament compression side cells.Sixteen subjects with bimaxillary dentoalveolar protrusion requiring extraction of all first premolars as part of orthodontic treatment were selected. Extractions were carried out pretreatment from control group. In the experimental group, a buccally directed spring, with force range of 70-120gms promoting bodily movement of maxillary first premolars was placed. Periodontal ligament was scraped from the middle third of the root from the compression side, the cells were isolated and cultured followed by HSP70 protein estimation with western blot analysis and the extend of nuclear damage was assessed with COMET assay.Western Blot analysis of HSP70 revealed a statistically significant increased expression of HSP70 (P0.05; CI=95%) in the force applied group compared with the control group. COMET assay could demonstrate significant amount of nuclear fragmentation in the compression side periodontal ligament cells in comparison to control group (P0.05; CI=95%).All these findings demonstrated, for the first time, that orthodontic force application augments release of HSP70 from periodontal ligament cells as a measure to restore tissue homeostasis. Further the study demonstrated that orthodontic forces induce DNA fragmentation, which is quantified more than double the amount observed in the control group.

Down’s syndrome is one of the most common human congenital genetic diseases and affected patients have increased risk of periodontal disease. To examine involvement of the disease with periodontal disease development, we established immortalized periodontal ligament cells obtained from a Down’s syndrome patient by use of SV40T-Ag and hTERT gene transfection. Expressions of SV40T-Ag and hTERT were observed in periodontal ligament cell-derived immortalized cells established from healthy (STPDL) and Down’s syndrome patient (STPDLDS) samples. Primary cultured periodontal ligament cells obtained from a healthy subject (pPDL) had a limited number of population doublings (DSCR-1 in STPDLDS is greater than that in STPDL. These results suggest that the newly established STPDLDS cell line may be a useful tool for study of periodontal disease in Down’s syndrome patients.

Decellularized tissue-engineered constructs have the potential to promote regeneration by providing a biomimetic extracellular matrix that directs tissue-specific regeneration when implanted in situ. Recently, the use of cell sheets has shown promising results in promoting periodontal regeneration. Here, we describe the fabrication of decellularized periodontal cell sheets with intact extracellular matrix structural and biological properties. Melt electro spun polycaprolactone (PCL) scaffolds are used as a carrier for the inherently fragile cell sheets, to provide support during the processes of decellularization. An optimized decellularization method is outlined using perfusion with a combination of NH4OH and Triton X-100 together with a DNase treatment step for DNA removal. The maintenance of extracellular matrix structural and biological integrity is important, and here we describe the assessment of these properties using immunostaining for extracellular matrix proteins and ELISA for growth factor quantification.

Periodontitis is a multi-etiologic infection characterized clinically by pathologic loss of the periodontal ligament and alveolar bone. Herpesviruses and specific bacterial species are major periodontal pathogens that cooperate synergistically in producing severe periodontitis. Cellular immunity against herpesviruses and humoral immunity against bacteria are key periodontal host defenses. Genetic, epigenetic, and environmental factors are modifiers of periodontal disease severity. MicroRNAs are a class of noncoding, gene expression-based, posttranscriptional regulatory RNAs of great importance for maintaining tissue homeostasis. Aberrant expression of microRNAs has been associated with several medical diseases. Periodontal tissue cells and herpesviruses elaborate several microRNAs that are of current research interest. This review attempts to conceptualize the role of periodontal microRNAs in the pathogenesis of periodontitis. The diagnostic potential of salivary microRNAs is also addressed. Employment of microRNA technology in periodontics represents an interesting new preventive and therapeutic possibility.

Background: The application of static compressive forces to periodontal ligament fibroblasts (PDLFs) in vivo or in vitro has been linked to the expression of biochemical agents and local tissue modifications that could be involved in maintaining homeostasis during orthodontic movement. An approach used for identifying mesenchymal cells, or a subpopulation of progenitor cells in both tumoral and normal tissues, involves determining the activity of aldehyde dehydrogenase (ALDH). However, the role of subpopulations of PDLF-derived undifferentiated cells in maintaining homeostasis during tooth movement remains unclear. Objective: This study aimed at analyzing the effect of applying a static compressive force to PDLFs on the activity of ALDH in these cells. Methods: PDLFs were distributed into two groups: control group (CG), where fibroblasts were not submitted to compression, and experimental group (EG), where fibroblasts were submitted to a static compressive force of 4 g/mm2 for 6 hours. The compressive force was applied directly to the cells using a custom-built device. ALDH activity in the PDLFs was evaluated by a flow cytometry assay. Results: ALDH activity was observed in both groups, but was significantly lower in EG than in CG after the application of a static compressive force in the former. Conclusion: Application of a static compressive force to PDLFs decreased ALDH activity.

The objective of the present study is to describe the stress and displacement patterns created by clear aligners and composite attachments bonded with the acid-etch technique on the labial surface of the maxillary first upper molar during its distalization. Maxillary molar distalization is a clinical orthodontics procedure used to move the first maxillary molar distally. The procedure is useful in patients with some Class II malocclusion allowing the first molar to move into a Class I relationship and the correction of associated malocclusion features. Three finite element models were designed to simulate the alveolar bone, molar tooth, periodontal ligament, aligner, and composite attachments. The first model had no composite attachment, the second model had a vertical rectangular attachment, and the third model had a newly designed attachment. A loading method was developed that mimicked the aligner’s molar distal movement. PDL was set as a viscoelastic material with a nonlinear mechanical response. von Mises and maximum principal stresses and tooth displacement patterns were analyzed using dedicated software. All the configurations showed some form of clockwise rotation in addition to the distal movement. The crown portion of the tooth showed maximum displacement in all three models; however, in the absence of attachment, the root apex moved in the opposite direction which was compatible with uncontrolled tipping movement. Simulations with attachments exhibited the best performance regarding the movement patterns. The third group, with the newly designed attachment, exhibited the best performance concerning stress distribution (principal stress and von Mises stresses) and higher stresses in the periodontal ligament and tooth. Incorporating a vertical rectangular attachment in a clear aligner resulted in the reduction of mesiodistal tipping tendency during molar distalization. The third model was the most efficient considering both displacement pattern and stress distribution. The level of stress generated by the third model needs to be further investigated in future studies.

The purpose of the is to provide an update on our existing considerate of LANAP and LAPIP (LASER-assisted new attachment procedure and LASER-assisted peri-implantitis procedure). The search for bio-medical literature on LANAP and LAPIP was conducted in PubMed, Embase, and Google Scholar scientific databases. This review underlines that LANAP can improve clinical periodontal parameters (like probing pocket depth and clinical attachment levels). Certain classic histologic studies have indicated the formation of new cementum, periodontal ligament (PDL), and alveolar bone with LANAP. Supported by several clinical and histologic investigations, LANAP was found to accelerate the re-establishment of damaged and diseased periodontium by the formation of new cementum, PDL, and alveolar bone, thus getting some fragrance of the “true periodontal regeneration”. More long-term randomized controlled clinical trials with higher sample sizes are required to reach at some conclusion concerning true periodontal regeneration with LANAP. Regarding LAPIP, its research is still in its infancy. In recent decades, LASER has come up as an auxiliary to a number of dental therapeutic modalities. The reason behind is a plethora of benefits that LASER offers for both the clinician and the patient. Blade-less, blood-less, and suture-less nature of LASER treatment is its major lead. LANAP has shown some data positive for true periodontal regeneration. Hence, it can be a valuable and excellent tool in periodontal armamentarium of general dental practitioners and periodontists that can avoid traumatic regenerative periodontal surgeries. LAPIP can be used for saving ailing and failing dental implants as shown by certain case series and reports.

This scoping review is intended to synthesize the techniques proposed to model the tooth-periodontal ligament-bone complex (TPBC), while also evaluating the suggested periodontal ligament (PDL) material properties. It is concentrated on the recent advancements on the PDL and TPBC models, while identifying the advantages and limitations of the proposed approaches. Systematic searches were conducted up to December 2020 for articles that proposed PDL models to assess orthodontic tooth movement in Compendex, Web of Science, EMBASE, MEDLINE, PubMed, ScienceDirect, Google Scholar and Scopus databases. Although there have been many studies focused on the evaluation of PDL material properties through numerous modelling approaches, only a handful of approaches have been identified to investigate the interface properties of the PDL as a complete dynamical system (TPBC models). Past reviews on the analytical and experimental determination of the PDL properties already show a concerning range in reported output values-some nearly six orders of magnitude in difference-that strongly suggested the need for further investigation. Surprisingly, it has not yet been possible to determine a narrower range of values for the PDL material properties. Moreover, very few scientific approaches address the TPBC as an integrated complex system model. In consequence, current methods for capturing the PDL material behaviour in a clinical setting are limited and inconclusive. This synthesis encourages more systematic, pragmatic and phenomenological research in this area.

The aim of this study was to characterize a clonal human periodontal ligament (PDL) stem cell line (line 2-23 cells) cultured with root canal sealers based on methacrylate resin (SuperBond sealer; SB), bioactive glass (Nishika Canal Sealer BG; BG), or silicon (GuttaFlow 2; GF). The sealers were set in rubber molds to form sealer discs. Line 2-23 cells were cultured with or without the discs for 3 days. The cell viability was evaluated by direct cell counting and MTT assay. Inflammation-, PDL-, collagen-, and cell cycle-related gene expression was investigated by real-time RT-PCR. Collagen production was analyzed by Picro Sirius Red staining. Calcium ion concentration in the culture was measured by a QuantiChrom calcium assay kit. Line 2-23 cells survived when cultured with GF discs, but decreased cell viability was observed with SB and BG discs. The expression of inflammation-related genes was higher in cells cultured with SB discs, and expression of PDL-related genes was lower in cells exposed to SB and BG discs. These discs also down-regulated collagen production in line 2-23 cells. BG discs increased calcium ion concentration in the culture medium. Cells exposed to GF discs exhibited the same inflammation-, PDL-, collagen-, and cell cycle-related gene expression and collagen production as untreated cells. These results suggested that the characteristics of line 2-23 cells cultured with GF discs was highly resemble to untreated cells throughout the 3 days of the culture model.

Background Barrier membranes and bone substitute are major tools of guided tissue regeneration (GTR) after periodontal disease. Integrity of the periodontal ligament plays a key role in periodontal health, but its functionality fails to be fully re-established by GTR after disease or trauma. Microtissue models suggest an in vivo-like model to develop novel GTR approaches due to its three-dimensionality. This study aims to assess the effects of collagen membranes and bone substitute on cell viability, adhesion and gene expression of regenerative and inflammatory biomarkers by periodontal ligament cell (PDLC) microtissues. Methods Human PDLC microtissues and monolayers were cultured on collagen membranes or bone substitute. After 24h incubation, metabolic activity, focal adhesion, mRNA and protein production of collagen-type-I (COL1A1), periostin (POSTN), vascular endothelial growth factor (VEGF), angiogenin (ANG), interleukin (IL)6 and IL8 were measured by resazurin-based toxicity assay, focal adhesion staining, quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Results PDLC microtissues and monolayers were viable on collagen membranes and bone substitute, but microtissues were less metabolically active. Dominant staining of actin filaments was found in PDLC microtissues on collagen membranes. COL1A1, POSTN, VEGF, ANG and IL6 were modulated in PDLC microtissues on bone substitute, while there were no significant changes on collagen membranes. PDLC monolayers showed a different character of gene expression changes. Conclusion PDLC microtissues and monolayers react diversely to collagen membranes and bone substitute. Further descriptive and mechanistic tests will be required to clarify the potential of PDLC microtissues as in vivo-like model for GTR. This article is protected by copyright. All rights reserved.

Osmotic swelling and residual stress are increasingly recognized as important factors in soft tissue biomechanics. Little attention has been given to residual stress in periodontal ligament (PDL) biomechanics despite its rapid growth and remodeling potential. Those tissues that bear compressive loads, e.g., articular cartilage, intervertebral disk, have received much attention related to their capacities for osmotic swelling. To understand residual stress and osmotic swelling in the PDL, it must be asked (1) to what extent, if any, does the PDL exhibit residual stress and osmotic swelling, and (2) if so, whether residual stress and osmotic swelling are mechanically significant to the PDL’s stress/strain behavior under external loading. Here, we incrementally built a series of computer models that were fit to uniaxial loading, osmotic swelling and residual stretch data. The models were validated with in vitro shear tests and in vivo tooth-tipping data. Residual stress and osmotic swelling models were used to analyze tension and compression stress (principal stress) effects in PDL specimens under external loads. Shear-to-failure experiments under osmotic conditions were performed and modeled to determine differences in mechanics and failure of swollen periodontal ligament. Significantly higher failure shear stresses in swollen PDL suggested that osmotic swelling reduced tension and thus had a strengthening effect. The in vivo model’s first and third principal stresses were both higher with residual stress and osmotic swelling, but smooth stress gradients prevailed throughout the three-dimensional PDL anatomy. The addition of PDL stresses from residual stress and osmotic swelling represents a unique concept in dental biomechanics.

Background This study aimed to investigate, if different physiological concentrations of vitamin D (25(OH)D3) and single nucleotide polymorphisms in vitamin D receptor (VDR) gene have an impact on gene expression in human periodontal ligament (hPDL) fibroblasts induced by simulated orthodontic compressive strain. Methods A pool of hPDL fibroblasts was treated in absence or presence of 25(OH)D3 in 3 different concentrations (10, 40 and 60 ng/ml). In order to evaluate the role of single nucleotide polymorphisms in the VDR gene, hPDL fibroblasts from 9 patients were used and treated in absence or presence of 40 ng/ml 25(OH)D3. Each experiment was performed with and without simulated orthodontic compressive strain. Real-time PCR was used for gene expression and allelic discrimination analysis. Relative expression of dehydrocholesterol reductase (DHCR7), Sec23 homolog A, amidohydrolase domain containing 1 (AMDHD1), vitamin D 25-hydroxylase (CYP2R1), Hydroxyvitamin D-1-α hydroxylase, receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), cyclooxygenase-2 (COX-2) and interleukin-6 (IL6) was assessed. Three single nucleotide polymorphisms in VDR were genotyped. Parametric or non-parametric tests were used with an alpha of 5%. Results RANKL, RANKL:OPG ratio, COX-2, IL-6, DHCR7, CYP2R1 and AMDHD1 were differentially expressed during simulated orthodontic compressive strain (p RANKL:OPG ratio was downregulated by all concentrations (10 ng/ml, 40 ng/ml and 60 ng/ml) of 25(OH)D3 (mean = 0.96 ± 0.68, mean = 1.61 ± 0.66 and mean = 1.86 ± 0.78, respectively) in comparison to the control (mean 2.58 ± 1.16) (p CYP2R1 gene expression was statistically modulated by the different 25(OH)D3 concentrations applied (p = 0.008). Samples from individuals carrying the GG genotype in rs739837 presented lower VDR mRNA expression and samples from individuals carrying the CC genotype in rs7975232 presented higher VDR mRNA expression (p Conclusions Simulated orthodontic compressive strain and physiological concentrations of 25(OH)D3 seem to regulate the expression of orthodontic tooth movement and vitamin-D-related genes in periodontal ligament fibroblasts in the context of orthodontic compressive strain. Our study also suggests that single nucleotide polymorphisms in the VDR gene regulate VDR expression in periodontal ligament fibroblasts in the context of orthodontic compressive strain.

Orthodontic treatment that takes a long time carries a large risk of complications such as caries or root resorption. Various surgical and nonsurgical interventions have been performed, but non-surgical interventions are currently not widely accepted by orthodontists. Low Intensity Pulsed Ultrasound (LIPUS) is a form of non-invasive technology that has been used in the medical field for more than six decades. In the field of dentistry, LIPUS stimulation has been studied, among others, to improve bone remodelling, regeneration of cementum, gingiva and periodontal ligament. This article aims to review the mechanism of LIPUS in orthodontic tooth movement. This review is expected to become a clinical practice guide to shorten the duration of orthodontic treatment using LIPUS in the future.

Statement of problem There is a long-held assumption that teeth are superior to implants because the periodontal ligament (PDL) confers a preeminent defense against biologic and mechanical challenges. However, adequate analysis of the literature is lacking. As a result, differential treatment planning of tooth- and implant-supported restorations has been compromised. Purpose Given an abundance and diversity of research, the purpose of this mapping review was to identify basic scientific gaps in the knowledge of how teeth and implants respond to biologic and mechanical loads. The findings will offer enhanced evidence-based clinical decision-making when considering replacement of periodontally compromised teeth and the design of implant prostheses. Material and methods The online databases PubMed, Science Direct, and Web of Science were searched. Published work from 1965 to 2020 was collected and independently analyzed by both authors for inclusion in this review. Results A total of 108 articles met the inclusion criteria of clinical, in vivo, and in vitro studies in the English language on the periradicular and peri-implant bone response to biologic and mechanical loads. The qualitative analysis found that the PDL's enhanced vascularity, stem cell ability, and resident cells that respond to inflammation allow for a more robust defense against biologic threats compared with implants. While the suspensory PDL acts to mediate moderate loads to the bone, higher compressive stress and strain within the PDL itself can initiate a biologic sequence of osteoclastic activity that can affect changes in the adjacent bone. Conversely, the peri-implant bone is more resistant to similar loads and the threshold for overload is higher because of the absence of a stress or strain sensitivity inherent in the PDL. Conclusions Based on this mapping review, teeth are superior to implants in their ability to resist biologic challenges, but implants are superior to teeth in managing higher compressive loads without prompting bone resorption.

Introdução: Um dos principais traumatismos dentários com graves consequências que acomete a população é a avulsão dentária, caracterizada pela completa exarticulação do dente para fora do seu alvéolo. Como consequência desse trauma, as fibras do ligamento periodontal, cemento e polpa são agredidas e pode ocorrer a reabsorção radicular. Devido à eficácia do uso da laserterapia de baixa potência (low level laser therapy – LLLT) em tratamentos periodontais e endodônticos, seu uso parece promissor em casos de avulsão dentária, podendo aumentar as taxas de sucesso. Objetivo: Realizar revisão narrativa para compreender a ação do LLLT sobre as propedêuticas endodônticas e periodonticas; apresentar o conhecimento atual e científico sobre a eficácia da LLLT na avulsão dentária; e observar falhas de pesquisas sobre o tema. Revisão de literatura: O LLLT reduz a dor pós-operatória na terapia e retratamento do canal radicular, tendo uma diminuição significativamente maior em relação aos anti-inflamatórios. Na periodontia há a redução de bactérias e cálculos, neutralização de endotoxina e diminuição de profundidade de bolsas. Poucos estudos avaliaram sua aplicação em tratamentos para reimplante dentário, os quais mostraram uma melhora a cicatrização, aumento na espessura da camada de dentina reacional e diminuição da inflamação. Considerações finais: A irradiação do LLLT promove reações bioquímicas, originando a estimulação do reparo tecidual, regeneração e redução dos processos inflamatórios, podendo ser um tratamento promissor para casos de avulsão e reimplante dentários. Mais pesquisas devem ser realizadas.

Aim: An optimum storage medium is required to preserve the viability of the periodontal ligament cells of the avulsed tooth. Although it has been suggested by some researchers that it would be suitable to store the avulsed tooth in water or saliva, milk has been considered the most appropriate storage medium. Although milk has been shown to be more effective for long durations, short-term results are contradictory. Thus, the purpose of this study was to assess in vitro capacity of four storage media at room temperature with mitochondrial function analysis to maintain the viability of periodontal ligament fibroblasts over different time periods.Material and Methods: Periodontal ligament samples were isolated from second premolars for extracted orthodontic reasons. Pasteurized long-life milk, saliva, tap water, and distilled water were used to examine periodontal ligament cell viability. The exposure periods were for 60, 120, and 240 min and cell viability were evaluated using the XTT assay.Results: The count of living cells in milk was found to be significantly higher than in other storage media after 60, 120, and 240 minutes. The mean number of viable cells after 240 min in all storage media except distilled water was significantly lower than the average number of viable cells after 60 min (p

It is a well-known concept that bone remodeling occurs during orthodontic tooth movement. The orthodonticliterature is vastly full of information about the changes occurring on the periodontal ligament level.However, changes occurring in the alveolar bone are being elucidated. What we know about bone resorptionhas changed a lot in the last few decades. The osteoclast is the only cell to nibble and breakdown the bone,and also aids in formation and resorption of bone tissue. In this review, we briefly describe the phases andtheories of tooth movement and also the changes involved during orthodontic tooth movement.

INTRODUCTION Systemic scleroderma (SSc) is a progressive autoimmune multisystem disease affecting several organs. In the oral cavity, its manifestations include enlarged periodontal ligament, xerostomia, microsomia, alveolar bone loss, and premature teeth loss. A removable prosthesis would not be a treatment option due to loss of hand dexterity, reduced chewing capacity, microsomia, and xerostomia in these patients. Alternatively, implant-supported fixed restorations are a plausible treatment for these patients. However, there is very limited literature showing implant survival rate in patients with SSc for a long follow-up. CASE PRESENTATION A 57-year-old female patient with SSc presented to our clinic. She was diagnosed with SSc 25 years ago. Initial clinical and radiological examination revealed that she showed slight to moderate chronic periodontitis, tooth cavities, remaining tooth tips, and a partial edentulism in the posterior areas. A total of seven implants were placed at different time points. The remaining upper teeth were crowned. At 4.8 years follow-up, the placed implants showed no sign of peri-implant disease. CONCLUSION This case report indicated that 4.8 years of follow-up revealed good oral hygiene and clinically or radiologically no sign of peri-implant disease around the implants in a patient with SSc. Implant-supported fixed restoration could be a viable treatment approach in these patients.

BACKGROUND/AIMS Pre-transplant blood transfusions have previously shown a positive effect on organ allograft survival in humans and various animal species. The aims of this study were, first, to evaluate the effect of pre-transplant donor-specific blood transfusions on periodontal healing of fully developed allotransplanted teeth in monkeys; and second, to investigate the immune response against donor antigens and to determine a possible correlation between alloimmune reactions and histopathological signs of rejection. MATERIAL AND METHODS Twenty monkeys (Cercopithecus aethiops) were divided into ten pairs with similar sizes of incisors. One monkey in each pair gave three transfusions to the other monkey with 1-week intervals. One week after the last transfusion, each pair exchanged simultaneously a central maxillary incisor and a lateral mandibular incisor. The corresponding central maxillary and mandibular lateral incisors were autotransplanted to the contralateral sockets. All teeth were treated endodontically per-operatively. Histocompatibility was evaluated by mixed lymphocyte culture before the first transfusion, while alloantibodies and cell-mediated alloresponses were measured before transfusions and at 2 and 8 weeks after transplantation. All animals were sacrificed 8 weeks after tooth transplantation. Serial sections of the transplanted teeth were quantified histologically. RESULTS Mixed lymphocyte cultures showed positive reactions in 19 of 20 cases, indicating incompatibility. The majority of the monkeys developed antibodies towards the tooth donor. Cell-mediated cytotoxicity was negative in all monkeys. Histoquantification revealed a mean score of 70% normal periodontal ligament (PDL) in autotransplanted teeth, with 5% ankylosis. The allografts had a mean score of 17% normal PDL and 63% ankylosis, with no significant influence of transfusion. However, in the mandibular grafts, a tendency towards a positive transfusion effect was seen. CONCLUSIONS Donor-specific blood transfusion did not reduce ankylosis in tooth allografts. The healing of mandibular incisor tooth allografts was improved, but not that of maxillary incisors. Donor-specific antibodies showed no effect on the survival of allograft PDL.

Periodontitis, a human chronic inflammatory disease, has affected the lives of millions of individuals. Periodontal ligament stem cells (PDLSCs), derived from the periodontal ligament, exhibit tissue specificity and impaired differentiation ability and are closely associated with tissue regeneration in periodontitis. Klotho, a single-pass transmembrane protein, has been reported to positively affect H2 O2 -induced oxidative stress and inflammation in PDLSCs. The ultimate damage of oxidative stress stimulation in PDLSCs was cell apoptosis, which was also the major lesion in periodontitis. Thus, the present study aimed to figure out the effect of klotho on H2 O2 -injured PDLSCs and its underlying mechanism to provide new therapeutic targets in periodontitis. The expression of klotho and uncoupling protein 2 (UCP2) was investigated in the gingival tissues, gingival crevicular fluid (GCF), and periodontal ligament stem cells (PDLSCs) in patients with chronic periodontitis. Then, under klotho treatment, oxidative stress was evaluated by measuring SOD and GSH-PX levels. Cell apoptosis and cell necrosis were also detected by measuring the cell death-relevant proteins, including Caspase-3, BAX, Bcl, MLKL, RIP1, and RIP3. Finally, a rescue assay was performed by inhibiting the expression of UCP2. The results showed that klotho and UCP2 were downregulated in patients with chronic periodontitis. In addition, klotho upregulated the production of UCP2 in H2 O2 -treated PDLSCs. Klotho inhibited H2 O2 -induced oxidative stress and cellular loss in PDLSCs, moreover, the rescue assay suggested that UCP2 knockdown suppressed the effects of klotho on PDLSCs. In conclusion, this study showed that klotho inhibits H2 O2 -induced oxidative stress and apoptosis in PDLSCs by regulating UCP2 expression. This novel discovery might provide a potential target for chronic periodontitis treatment.

Silicate bioglass is of great importance in bone engineering because of its excellent bioactivity and osteogenic effects. In this study, hydroxyapatite-like bioactive glass based on the xSiO2-CaO-P2O5 (x = 30, 45, 60 and 90 mol.%, Ca/P = 1.67) system was synthesized by the sol-gel method, and the corresponding structural evolution, apatite-forming ability and cytotoxicity were systematically investigated. The results suggest that both a higher heat treatment temperature and a lower SiO2 content increase the crystallinity tendency of the bioglass, and the samples become obviously compact as the SiO2 amount increases from 30 to 90 mol.%. Compared with the samples with higher SiO2 content, the 30Si sample shows more remarkable internal connected mesoporous structures, with a higher specific surface area up to 129.12 m2/g, exhibiting excellent hydroxyapatite formation in simulated body fluid. Moreover, no obvious inhibitory effect was presented on human periodontal ligament cells (hPDLCs) for any of the silicate glass samples.

BACKGROUND/AIM The high rate of root resorption resulting from tooth replantation represents a serious clinical problem. In order to prevent ankylosis and replacement resorption, the contemporary literature highlights the importance of using a flexible stabilization for traumatized teeth. For this purpose, orthodontic devices may be promising for obtaining a better prognosis and periodontal repair. The aim of this study was to evaluate the effect of an active splinting protocol with controlled force in dog's teeth following replantation. MATERIAL AND METHODS Sixty premolar roots from three dogs were used. They were submitted to endodontic treatment, hemisected, atraumatically extracted and subsequently replanted. They were divided into four groups: Passive Stabilization (n = 20)-after 20 min in a dry medium; Active Stabilization (n = 20)-after 20 min in a dry medium; Negative control (n = 10)-immediate replantation and passive Stabilization; and Positive control (n = 10)-90 min of extra-alveolar time and passive Stabilization. The samples were collected and submitted to histologic processing. They were then evaluated for the count of inflammatory cells, expression of neurotrophin 4, osteoclasts, apoptotic cells and collagen fibres. The results were submitted to ANOVA or Kruskal-Wallis statistical tests followed by Tukey or Dunn post-tests (α = 5%). RESULTS Passive Stabilization with orthodontic brackets without traction used after replantation had the highest number of inflammatory cells (p = .0122), osteoclasts (p = .0013) and percentage of collagen fibres in the periodontal ligament (p

ObjectivesOrthodontic treatment in adult patients predisposed to mild or severe periodontal disease is challenging for orthodontists. Orthodontic malpractice or hyper-occlusal forces may aggravate periodontitis-induced destruction of periodontal tissues, but the specific mechanism remains unknown. In the present study, the combined effect of mechanical stress and tumor necrosis factor (TNF)-α on the inflammatory response in human periodontal ligament stromal cells (hPDLSCs) was investigated.Materials and methodshPDLSCs from 5 healthy donors were treated with TNF-α and/or subjected to cyclic tensile strain (CTS) of 6% or 12% elongation with 0.1 Hz for 6- and 24 h. The gene expression of interleukin (IL)-6, IL-8 and cell adhesion molecules VCAM and ICAM was analyzed by qPCR. The protein levels of IL-6 and IL-8 in conditioned media was measured by ELISA. The surface expression of VCAM-1 and ICAM-1 was quantified by immunostaining followed by flow cytometry analysis.ResultsTNF-α-induced IL-6 gene and protein expression was inhibited by CTS, whereas TNF-α-induced IL-8 expression was decreased at mRNA expression level but enhanced at the protein level in a magnitude-dependent manner. CTS downregulated the gene expression of VCAM-1 and ICAM-1 under TNF-α stimulation, but the downregulation of the surface expression analyzed by flow cytometry was observed chiefly for VCAM-1.ConclusionsOur findings show that mechanical force differentially regulates TNF-α-induced expression of inflammatory mediators and adhesion molecules at the early stage of force application. The effect of cyclic tensile strain is complex and could be either anti-inflammatory or pro-inflammatory depending on the type of pro-inflammatory mediators and force magnitude.Clinical relevanceOrthodontic forces regulate the inflammatory mediators of periodontitis. The underlying mechanism may have significant implications for future strategies of combined periodontal and orthodontic treatment.

Periodontal disease is a disease that attacks the tissue that surrounds and supports the teeth consisting of the gingiva, periodontal ligament, cementum and alveolar bone. In patients who have a history of systemic diseases such as diabetes, the patient's oral health can also be affected, one of which is the appearance of periodontal disease. Periodontal disease is related to diabetes mellitus where diabetes mellitus with uncontrolled glucose levels is a risk factor that aggravates periodontal diseases such as gingivitis and periodontitis. Extraction is the act of taking teeth and tooth roots from the socket involving bone tissue and soft tissue in the oral cavity. Tooth extraction or extraction is a treatment procedure that is quite often performed by. There are various factors that influence tooth extraction, including sociodemography. Extraction is more common in patients with low levels of education than in societies with higher levels of education. This condition probably occurs because of the level of individual knowledge. Diabetes mellitus is a chronic chronic disease that has a prevalence that continues to increase every year, this disease is caused by metabolic disorders so that the body cannot control the levels of sugar in the blood. The immune response is impaired in diabetic patients.

Orthodontic tooth movement (OTM) depends on periodontal ligament cells (PDLCs) sensing biomechanical stimuli and subsequently releasing signals to initiate alveolar bone remodeling. However, the mechanisms by which PDLCs sense biomechanical stimuli and affect osteoclastic activities are still unclear. This study demonstrates that the core circadian protein aryl hydrocarbon receptor nuclear translocator–like protein 1 (BMAL1) in PDLCs is highly involved in sensing and delivering biomechanical signals. Orthodontic force upregulates BMAL1 expression in periodontal tissues and cultured PDLCs in manners dependent on ERK (extracellular signal–regulated kinase) and AP1 (activator protein 1). Increased BMAL1 expression can enhance secretion of CCL2 (C-C motif chemokine 2) and RANKL (receptor activator of nuclear factor–κB ligand) in PDLCs, which subsequently promotes the recruitment of monocytes that differentiate into osteoclasts. The mechanistic delineation clarifies that AP1 induced by orthodontic force can directly interact with the BMAL1 promoter and activate gene transcription in PDLCs. Localized administration of the ERK phosphorylation inhibitor U0126 or the BMAL1 inhibitor GSK4112 suppressed ERK/AP1/BMAL1 signaling. These treatments dramatically reduced osteoclastic activity in the compression side of a rat orthodontic model, and the OTM rate was almost nonexistent. In summary, our results suggest that force-induced expression of BMAL1 in PDLCs is closely involved in controlling osteoclastic activities during OTM and plays a vital role in alveolar bone remodeling. It could be a useful therapeutic target for accelerating the OTM rate and controlling pathologic bone-remodeling activities.

Made available in DSpace on 2021-06-25T11:02:04Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Dinosaurs possess a form of tooth attachment wherein an unmineralized periodontal ligament suspends each tooth within a socket, similar to the condition in mammals and crocodylians. However, little information is known about tooth attachment and implantation in their close relatives, the silesaurids. We conducted a histological survey of several silesaurid taxa to determine the nature of tooth attachment in this phylogenetically and paleoecologically important group of archosaurs. Our histological data demonstrate that these early dinosauriforms do not exhibit the crocodilian/dinosaur condition of a permanent gomphosis, nor the rapid ankylosis that is plesiomorphic for amniotes. Instead, all sampled silesaurids exhibit delayed ankylosis, a condition in which teeth pass through a prolonged stage where the teeth are suspended in sockets by a periodontal ligament, followed by eventual mineralization and fusion of the tooth to the jaws. This suggests that tooth attachment in crocodylians and dinosaurs represent the further retention of an early ontogenetic stage compared to silesaurids, a paedomorphic trend that is mirrored in the evolution of synapsid tooth attachment. It also suggests that the dinosaur and crocodylian gomphosis was convergently acquired via heterochrony or, less likely, that the silesaurid condition represents a reversal to a plesiomorphic state. Moreover, if Silesauridae is nested within Ornithischia, a permanent gomphosis could be convergent between the two main dinosaur lineages, Ornithischia and Saurischia. These results demonstrate that dental characters in early archosaur phylogenies must be chosen and defined carefully, taking into account the relative duration of the different phases of dental ontogeny. Departamento de Biologia Universidade de São Paulo Department of Biological Sciences University of Alberta Faculty of Dentistry Oral & Craniofacial Sciences King's College London Department of Geosciences Virginia Tech Programa de Pós-Graduação em Biologia Animal Instituto de Biociências Letras e Ciências Exatas UNESP Campus de São José do Rio Preto Natural History Museum of Utah and Department of Geology & Geophysics University of Utah Laboratório de Estratigrafia e Paleobiologia Departamento de Geociências Universidade Federal de Santa Maria Museu de Ciências Naturais Secretaria do Meio Ambiente e Infraestrutura Programa de Pós-Graduação em Biologia Animal Instituto de Biociências Letras e Ciências Exatas UNESP Campus de São José do Rio Preto

A novel 2-part varnish system containing chitosan nanoparticles (part 1) and chitosan-grafted hydroxyapatite precursor nanocomplex (part 2) was developed to condition the root-end dentin using the principle of biomineralization while rendering both antimicrobial efficacy and bioactivity. This in vitro study aimed to characterize and assess the effectiveness of the chitosan nanoparticles and chitosan-grafted hydroxyapatite precursor nanocomplex containing self-mineralizing antibacterial tissue repair varnish to condition as well as seal root-end dentin during endodontic microsurgery.In phase 1, the antibacterial properties and cellular response of the varnish were characterized. The antibacterial activity and cellular responses were evaluated using Enterococcus faecalis and periodontal ligament (PDL) fibroblasts, respectively. In phase 2, a resected root-end model was used to apply the 2-part varnish and examine the dentin-varnish interface using transmission electron microscopy. The percentage of root end sealed with time was determined using scanning electron microscopy (n = 6/time point). Statistical analysis was performed using 1-way analysis of variance where applicable.The part 1 and 2 of the varnish displayed significant antibacterial activity and reduced bacterial adherence/survival (P.01). The attachment and spreading of PDL fibroblasts on the varnish-conditioned dentin was enhanced compared with unconditioned dentin (P.01). In the resected root-end model, the 2-part varnish displayed a biomineralized varnish layer with close interaction with the subsurface dentin. Root-end coverage with the biomineralized layer increased with incubation time (P.01), reaching approximately 95% coverage after 24 hours.The 2-part varnish system effectively conditioned/sealed the root end with a biomineralized layer while reducing bacterial load and promoting PDL fibroblast attachment. This therapeutic modification of root-end dentin could provide optimal conditions to enhance healing and improve prognosis in teeth with root-end cracks after endodontic microsurgery.

We aimed to study the influence of attachment on central incisor movement control using invisible orthodontics with different translation or rotation targets. In this study, cone-beam computerised tomography was used to scan one 15-year-old volunteer’s teeth. Three-dimensional models of the mandibular central incisor, removable orthodontic appliance, and a rectangular attachment were reconstructed. A non-linear finite element simulation was used to analyse the influence of attachment on the stress distribution of the periodontal ligament of the central incisor under tooth rotation, mesial translation, and labial-lingual translation. For mandibular central incisor correction, using rectangular attachments increased the translation by up to 9.6%, increased the maximum stress on the periodontal ligament during the mesial translation correction, and reduced unwanted labial-lingual tilt by up to 40% during the rotation of the tooth. However, wearing an attachment during labial-lingual translation had no significant effect on the orthodontic results of the mandibular central incisor. In the mandibular central incisor’s invisible orthodontic, the rectangular attachment appliance increased the displacement and alleviated the side effect after applying mesial translation and tooth rotation. For labial-lingual translation, the application of a rectangular attachment had no pronounced effect on the results.

Rebuilding the tooth-supporting tissues (periodontium) destroyed by periodontitis remains a clinical challenge. Periodontal ligament cells (PDLCs), multipotent cells within the periodontal ligament (PDL), differentiate and form new PDL and mineralized tissues (cementum and bone) during native tissue repair in response to specific extracellular matrix (ECM) cues. Thus, harnessing ECM cues to control PDLC activity ex vivo, and ultimately, to design a PDLC delivery vehicle for tissue regeneration is an important goal. In this study, poly(ethylene glycol) hydrogels were used as a synthetic PDL ECM to interrogate the roles of cell–matrix interactions and cell-mediated matrix remodeling in controlling PDLC activity. Results showed that PDLCs within matrix metalloproteinase (MMP)-degradable hydrogels expressed key PDL matrix genes and showed a six to eightfold increase in alkaline phosphatase (ALP) activity compared with PDLCs in nondegradable hydrogel controls. The increase in ALP activity, commonly considered an early marker of cementogenic/osteogenic differentiation, occurred independent of the presentation of the cell-binding ligand RGD or soluble media cues and remained elevated when inhibiting PDLC-matrix binding and intracellular tension. ALP activity was further increased in softer hydrogels regardless of degradability and was accompanied by an increase in PDLC volume. However, scaffolds that fostered PDLC ALP activity did not necessarily promote hydrogel ECM mineralization. Rather, matrix mineralization was greatest in stiffer, MMP-degradable hydrogels and required the presence of soluble media cues. These divergent outcomes illustrate the complexity of the PDLC response to ECM cues and the limitations of current scaffold materials. Nevertheless, key biomaterial design principles for controlling PDLC activity were identified for incorporation into scaffolds for periodontal tissue regeneration. IMPACT STATEMENT: Engineered scaffolds are an attractive approach for delivering periodontal ligament cells (PDLCs) to rebuild the tooth-supporting tissues. Replicating key extracellular matrix (ECM) cues within tissue engineered scaffolds may maximize PDLC potential. However, the identity of important ECM cues and how they can be harnessed to control PDLC activity is still unknown. In this study, matrix degradability, cell–matrix binding, and stiffness were varied using synthetic poly(ethylene glycol) hydrogels for three-dimensional PDLC culture. PDLCs exhibited dramatic and divergent responses to these cues, supporting further investigation of ECM-replicating scaffolds for control of PDLC behavior and periodontal tissue regeneration.

This study investigated the effect of three commercial calcium silicate-based materials (CSBM) on cytotoxicity and pro-and anti-inflammatory cytokines production in cultured human periodontal ligament stem cells (hPDLSCs). Culture of hPDLSCs was established and characterized. Extracts of Bio-C Sealer (Angelus, Londrina, PR, Brazil), MTA Fillapex (Angelus, Londrina, PR, Brazil) and PBS Cimmo HP (Cimmo Soluções em Saúde, Pouso Alegre, MG, Brazil) were prepared by placing cement specimens (5 x 3 mm) in culture medium. Then, the extracts were serially two-fold diluted (1, 1:2, 1:4, 1:8, 1:16) and inserted into the cell-seeded wells for 24, 48 and 72 h for MTT assays. TNF-α and IL-10 cytokines were quantified by ELISA at 24h-cell supernatants. Data were analyzed by ANOVA and Tukey’s test (α = 0.05). All CSBM exhibited some cytotoxicity that varied according to extract concentration and time of evaluation. MTA Fillapex presented the highest cytotoxic effects with significant reduction of metabolic activity/cell viability when compared to Bio-C Sealer and Cimmo HP®. TNF-α was significantly upregulated by the three tested cements (p < 0.05) while only MTA Fillapex significantly upregulated IL-10 in comparison to control. Taken collectively, the results showed that PBS Cimmo HP®, Bio-C Sealer and MTA Fillapex present mild and transient cytotoxicity and slightly induced TNF-α production. MTA Fillapex upregulated IL-10 release by hPDLSCs. Resumo Este estudo investigou o efeito de três materiais comerciais à base de silicato de cálcio (CSBM) na citotoxicidade e na produção de citocinas pró e antiinflamatórias em células-tronco do ligamento periodontal humano (hPDLSCs). Cultura de hPDLSCs foi estabelecida e caracterizada. Extratos de Bio-C Sealer (Angelus, Londrina, PR, Brasil), MTA Fillapex (Angelus, Londrina, PR, Brasil) e PBS Cimmo HP® (Cimmo Soluções em Saúde, Pouso Alegre, MG, Brasil) foram preparados com a colocação de espécimes dos cimentos (5 x 3 mm) em meio de cultura. Em seguida, os extratos foram diluídos (1, 1: 2, 1: 4, 1: 8, 1:16) e inseridos nos poços semeados de células para ensaio de citotoxicidade por meio de MTT por 24, 48 e 72 h. As citocinas TNF-α e IL-10 foram quantificadas por ELISA em sobrenadantes de células de 24 h. Os dados foram analisados por ANOVA e teste de Tukey (α = 0,05). Todos os CSBM exibiram alguma citotoxicidade que variou de acordo com a concentração do extrato e o tempo de avaliação. O MTA Fillapex apresentou os maiores efeitos citotóxicos com redução significativa da atividade metabólica / viabilidade celular quando comparado ao Bio-C Sealer e Cimmo HP®. O TNF-α foi regulado positivamente pelos três cimentos testados (p