Evaluation of midpalatal suture maturation stage in 5- to 20-year-olds using cone-beam computed tomography.

INTRODUCTION: This study aimed to evaluate the midpalatal suture (MPS) maturation stages using the cone-beam computed tomography classification method in Chinese children aged 5-10 years, adolescents aged 11-15 years, and postadolescents aged 16-20 years and identify a correlation between maturation stage and age and sex. METHODS: Axial sections of tomographic images from 717 participants (369 female and 348 male participants) aged 5-20 years were used to classify the maturation stage of the MPS (stages A, B, C, D, and E). Kappa statistics were used to evaluate the measurement error. The chi-square test was applied to analyze the differences in the distribution of MPS stages by age group and by sex among all participants, as well as the adolescent group. The Fisher exact test was employed to assess the differences in MPS stage distribution by sex among children aged 5-10 years and among the postadolescent group. The Mann-Whitney U test was used to assess the potential variance in age distribution between stages C and D. RESULTS: The most prevalent maturation stage was stage C (40.3%). Of the total population, 69.4% had MPS in stages A, B, or C. A significant difference in age distribution was observed between stage C and stage D (P <0.001). The distribution of the MPS maturation stage significantly varied by age group (P <0.001) and sex (P <0.001). CONCLUSIONS: The distribution of participants in advanced maturation stages increases with age. Female patients generally experience earlier MPS maturation than male patients, particularly between the ages of 11-20 years.

New Generation of Orthodontic Elastomeric Ligature to Prevent Enamel Demineralization In Vivo.

This study aimed to synthesize a novel elastomeric ligature with dimethylaminohexadecyl methacrylate (DMAHDM) grafted, providing a new strategy for improving the issue of enamel demineralization during fixed orthodontics. DMAHDM was incorporated into elastomeric ligatures at different mass fractions using ultraviolet photochemical grafting. The antibacterial properties were evaluated and the optimal DMAHDM amount was determined based on cytotoxicity assays. Moreover, tests were conducted to evaluate the in vivo changes in the mechanical properties of the elastomeric ligatures. To assess the actual in vivo effectiveness in preventing enamel demineralization, a rat demineralization model was established, with analyses focusing on changes in surface microstructure, elemental composition, and nanomechanical properties. Elastomeric ligatures with 2% DMAHDM showed excellent biocompatibility and the best antibacterial properties, reducing lactic acid production by 65.3% and biofilm bacteria by 50.0% within 24 h, without significant mechanical property differences from the control group (p > 0.05). Most importantly, they effectively prevented enamel demineralization in vivo, enhancing elastic modulus by 73.2% and hardness by 204.8%. Elastomeric ligatures incorporating DMAHDM have shown great potential for application in preventing enamel demineralization, providing a new strategy to solve this issue during fixed orthodontics.

Automatic soft-tissue analysis on orthodontic frontal and lateral facial photographs based on deep learning.

BACKGROUND: To establish the automatic soft-tissue analysis model based on deep learning that performs landmark detection and measurement calculations on orthodontic facial photographs to achieve a more comprehensive quantitative evaluation of soft tissues. METHODS: A total of 578 frontal photographs and 450 lateral photographs of orthodontic patients were collected to construct datasets. All images were manually annotated by two orthodontists with 43 frontal-image landmarks and 17 lateral-image landmarks. Automatic landmark detection models were established, which consisted of a high-resolution network, a feature fusion module based on depthwise separable convolution, and a prediction model based on pixel shuffle. Ten measurements for frontal images and eight measurements for lateral images were defined. Test sets were used to evaluate the model performance, respectively. The mean radial error of landmarks and measurement error were calculated and statistically analysed to evaluate their reliability. RESULTS: The mean radial error was 14.44 ± 17.20 pixels for the landmarks in the frontal images and 13.48 ± 17.12 pixels for the landmarks in the lateral images. There was no statistically significant difference between the model prediction and manual annotation measurements except for the mid facial-lower facial height index. A total of 14 measurements had a high consistency. CONCLUSION: Based on deep learning, we established automatic soft-tissue analysis models for orthodontic facial photographs that can automatically detect 43 frontal-image landmarks and 17 lateral-image landmarks while performing comprehensive soft-tissue measurements. The models can assist orthodontists in efficient and accurate quantitative soft-tissue evaluation for clinical application.

Novel antibacterial orthodontic elastomeric ligature with oral biofilm-regulatory ability to prevent enamel demineralization.

OBJECTIVES: To synthesize a novel antibacterial orthodontic elastomeric ligature incorporating dimethylaminohexadecyl methacrylate (DMAHDM) for the first time to prevent enamel demineralization during orthodontic therapy. METHODS: Various mass fractions of DMAHDM (ranging from 0 % to 20 %) were grafted onto commercial elastomeric ligatures using an ultraviolet photochemical grafting method and were characterized. The optimal DMAHDM concentration was determined based on biocompatibility and mechanical properties, and the antibacterial efficacy was evaluated in a whole-plaque biofilm model. TaqMan real-time polymerase chain reaction and fluorescence in situ hybridization were used to assess the microbial regulatory ability of the multispecies biofilms. Furthermore, an in vitro tooth demineralization model was established to explore its preventive effects on enamel demineralization. Statistical analysis involved a one-way analysis of variance and LSD post hoc tests at a significance level of 0.05. RESULTS: The elastomeric ligature containing 2 % mass fraction of DMAHDM exhibited excellent mechanical properties, favorable biocompatibility, and the most effective antibacterial ability against microorganisms, which decreased by almost two logarithms (P < 0.05). It significantly reduced the proportion of Streptococcus mutans in the multispecies plaque biofilm by 25 % at 72 h, leading to an enhanced biofilm microenvironment. Moreover, the novel elastomeric ligature demonstrated an obvious preventive effect on enamel demineralization, with an elastic modulus 30 % higher and hardness 62 % higher than those of the control group within 3 months (P < 0.05). SIGNIFICANCE: The integration of DMAHDM with an elastomeric ligature holds significant promise for regulating biofilms and preventing enamel demineralization in orthodontic applications.

Supragingival microbiome variations and the influence of Candida albicans in adolescent orthodontic patients with gingivitis.

Introduction: Gingivitis is a prevalent complication in adolescents undergoing fixed orthodontic treatments. However, changes in the supragingival microbiome associated with gingivitis and the impact of Candida albicans remain elusive. Therefore, we investigated supragingival microbiome discrepancy and C. albicans colonization in adolescent orthodontic patients with gingivitis. Methods: Dental plaques were collected from 30 gingivitis patients and 24 healthy adolescents, all undergoing fixed orthodontic treatment. The supragingival microbiome composition was analyzed using 16S rRNA sequencing. C. albicans colonization was determined using fungal culture and real-time quantitative polymerase chain reaction. Results: Our analysis revealed significantly heightened microbial diversity in the Gingivitis group. Notably, patients with gingivitis exhibited an enrichment of periodontal pathogens, such as Saccharibacteria (TM7) [G-1], Selenomonas, Actinomyces dentalis, and Selenomonas sputigena. Additionally, 33% of the gingivitis patients tested positive for C. albicans, exhibiting significantly elevated levels of absolute abundance, while all healthy patients tested negative. Significant differences in microbial composition were also noted between C. albicans-positive and -negative samples in the Gingivitis group. Conclusion: Significant disparities were observed in the supragingival microbiome of adolescent orthodontic patients with and without gingivitis. The presence of C. albicans in the supragingival plaque may alter the microbiome composition and potentially contribute to gingivitis pathogenesis.

• Adolescent patients undergoing fixed orthodontic treatment, with and without gingivitis, show significant differences in their marginal supragingival plaque microbiomes. • Adolescent patients with gingivitis exhibit a significantly higher rate of Candida albicans colonization than healthy individuals. • The colonization of C. albicans alters the composition of the marginal supragingival plaque microbiome in patients with gingivitis.

Global Research Trends and Focuses on Pierre Robin Sequence From 1992 to 2023: A Bibliometric Analysis of the Past 3 Decades.

There is currently a lack of scientific bibliometric analyses in the field of Pierre Robin sequence (PRS). Pierre Robin sequence is known for its clinical triad of micrognathia, glossoptosis, airway obstruction, and possible secondary cleft palate. These defects can lead to upper airway obstruction, sleep apnea, feeding difficulties, affect an individual's growth and development, education level, and in severe cases can be life-threatening. Through analysis of literature retrieved from the Web of Science Core Collection (WoSCC) database using Results Analysis and Citation Report and Citespace software, 933 original articles and reviews were included after manual screening. The overall trend for the number of annual publications and citations was increasing. On the basis of the analysis, airway evaluation and treatment, mandibular distraction osteogenesis (MDO), as well as descriptions of PRS characteristics have been the focus of research in this field. In addition, with advances in new technologies such as gene sequencing and expanding understanding of diseases among researchers, research on genetics and etiology related to PRS has become a growing trend.

Adipogenic differentiation effect of human periodontal ligament stem cell initial cell density on autologous cells and human bone marrow stromal cells.

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.

STSN-Net: Simultaneous Tooth Segmentation and Numbering Method in Crowded Environments with Deep Learning.

Accurate tooth segmentation and numbering are the cornerstones of efficient automatic dental diagnosis and treatment. In this paper, a multitask learning architecture has been proposed for accurate tooth segmentation and numbering in panoramic X-ray images. A graph convolution network was applied for the automatic annotation of the target region, a modified convolutional neural network-based detection subnetwork (DSN) was used for tooth recognition and boundary regression, and an effective region segmentation subnetwork (RSSN) was used for region segmentation. The features extracted using RSSN and DSN were fused to optimize the quality of boundary regression, which provided impressive results for multiple evaluation metrics. Specifically, the proposed framework achieved a top F1 score of 0.9849, a top Dice metric score of 0.9629, and an mAP (IOU = 0.5) score of 0.9810. This framework holds great promise for enhancing the clinical efficiency of dentists in tooth segmentation and numbering tasks.

Research progress in cell therapy for oral diseases: focus on cell sources and strategies to optimize cell function.

In recent years, cell therapy has come to play an important therapeutic role in oral diseases. This paper reviews the active role of mesenchymal stem cells, immune cell sources, and other cells in oral disorders, and presents data supporting the role of cell therapy in oral disorders, including bone and tooth regeneration, oral mucosal disorders, oral soft tissue defects, salivary gland dysfunction, and orthodontic tooth movement. The paper will first review the progress of cell optimization strategies for oral diseases, including the use of hormones in combination with stem cells, gene-modified regulatory cells, epigenetic regulation of cells, drug regulation of cells, cell sheets/aggregates, cell-binding scaffold materials and hydrogels, nanotechnology, and 3D bioprinting of cells. In summary, we will focus on the therapeutic exploration of these different cell sources in oral diseases and the active application of the latest cell optimization strategies.

Three-dimensional finite element analysis on the effects of maxillary protraction with an individual titanium plate at multiple directions and locations.

Objective: : A three-dimensional-printed individual titanium plate was applied for maxillary protraction to eliminate side effects and obtain the maximum skeletal effect. This study aimed to explore the stress distribution characteristics of sutures during maxillary protraction using individual titanium plates in various directions and locations. Methods: : A protraction force of 500 g per side was applied at forward and downward angles between 0° and 60° with respect to the Frankfort horizontal plane, after which the titanium plate was moved 2 and 4 mm upward and downward, respectively. Changes in sutures with multiple protraction directions and various miniplate heights were quantified to analyze their impact on the maxillofacial bone. Results: : Protraction angle of 0-30° with respect to the Frankfort horizontal plane exhibited a tendency for counterclockwise rotation in the maxilla. At a 40° protraction angle, translational motion was observed in the maxilla, whereas protraction angles of 50-60° tended to induce clockwise rotation in the maxilla. Enhanced protraction efficiency at the lower edge of the pyriform aperture was associated with increased height of individual titanium plates. Conclusions: : Various protraction directions are suitable for patients with different types of vertical bone surfaces. Furthermore, when the titanium plate was positioned lower, the protraction force exhibited an increase.

New generation of orthodontic devices and materials with bioactive capacities to improve enamel demineralization.

OBJECTIVE: The article reviewed novel orthodontic devices and materials with bioactive capacities in recent years and elaborated on their properties, aiming to provide guidance and reference for future scientific research and clinical applications. DATA, SOURCES AND STUDY SELECTION: Researches on remineralization, protein repellent, antimicrobial activity and multifunctional novel bioactive orthodontic devices and materials were included. The search of articles was carried out in Web of Science, PubMed, Medline and Scopus. CONCLUSIONS: The new generation of orthodontic devices and materials with bioactive capacities has broad application prospects. However, most of the current studies are limited to in vitro studies and cannot explore the true effects of various bioactive devices and materials applied in oral environments. More research, especially in vivo researches, is needed to assist in clinical application. CLINICAL SIGNIFICANCE: Enamel demineralization (ED) is a common complication in orthodontic treatments. Prolonged ED can lead to dental caries, impacting both the aesthetics and health of teeth. It is of great significance to develop antibacterial orthodontic devices and materials that can inhibit bacterial accumulation and prevent ED. However, materials with only preventive effect may fall short of addressing actual needs. Hence, the development of novel bioactive orthodontic materials with remineralizing abilities is imperative. The article reviewed the recent advancements in bioactive orthodontic devices and materials, offering guidance and serving as a reference for future scientific research and clinical applications.

Effects of Innervation on Angiogenesis and Osteogenesis in Bone and Dental Tissue Engineering.

The repair and regeneration of critical-sized bone defects remain an urgent challenge. Bone tissue engineering represents an exciting solution for regeneration of large bone defects. Recently, the importance of innervation in tissue-engineered bone regeneration has been increasingly recognized. The cross talk between nerve and bone provides important clues for bone repair and regeneration. Furthermore, the promotion of angiogenesis by innervation can accelerate new bone formation. However, the mechanisms involved in the promotion of vascular and bone regeneration by the nervous system have not yet been established. In addition, simultaneous neurogenesis and vascularization in bone tissue engineering have not been fully investigated. This article represents the first review on the effects of innervation in enhancing angiogenesis and osteogenesis in bone and dental tissue engineering. Cutting-edge research on the effects of innervation through biomaterials on bone and dental tissue repairs is reviewed. The effects of various nerve-related factors and cells on bone regeneration are discussed. Finally, novel clinical applications of innervation for bone, dental, and craniofacial tissue regeneration are also examined.

Using a structured light scanner to evaluate 3-dimensional soft-tissue changes after extracting 4 premolars in young adult female patients.

INTRODUCTION: Facial esthetics have always received much attention in orthodontic treatment, especially in young adult female patients. Three-dimensional (3D) soft-tissue changes after orthodontic extraction have not been fully explained. This study evaluated the 3D morphologic changes after orthodontic extraction in young female patients using a structured light scanner. METHODS: Forty-five adult female patients aged 20-25 years were enrolled in our study. The treatment group consisted of patients who received orthodontic treatment with 4 premolar extractions, and the control group was composed of young female volunteers who had not undergone any orthodontic treatment. To monitor the soft-tissue changes, 9 morphologic regions and 12 landmarks were identified for the 3D deviation analyses. The spatial deviations of landmarks and regions in the x, y, and z directions were constructed for quantitative analysis. Color map images were constructed to visualize soft-tissue displacement as a qualitative evaluation. The paired sample test was used to compare differences at the beginning of the experiment (T0) and after 24 months (T1) in both groups. An independent t test with Bonferroni correction was performed to compare differences between the treatment and control groups. A linear regression test was performed between incisor retraction and changes in the perioral tissues. RESULTS: Subtracting the effect of aging from the lip changes in the control group, the treatment group showed a statistically significant difference in the displacement of labrale superius (-1.37 mm), labrale inferius (-1.89 mm), the upper lip region (-0.98 mm), and the lower lip region (-1.36 mm) along the z-axis. No significant differences were found between the treatment and control groups in the temporal, parotideomasseteric, and buccal regions. Pearson correlation tests indicated a positive correlation between incisor tip retraction and changes in soft tissues (two-dimensional cephalometric analysis, 3D landmark measurements, and 3D regional measurements). The correlation coefficient ranged between 0.45 and 0.55. CONCLUSIONS: Three-dimensional soft-tissue changes were mainly concentrated in the upper and lower lip regions in adult female patients after the 4 premolars were extracted. For female patients aged 20-25 years with 4 extracted premolars, soft-tissue changes in the temporal, parotideomasseteric, and buccal regions were not clinically significant.

Adult female skeletal anterior open bite treated by customized lingual orthodontic appliance with miniscrews-assisted in vertical control for perfect orthodontic compensation: A case report with 5-year follow-up.

The benefits of lingual orthodontics go beyond appearance. In this case study, a 30-year-old female patient was treated with a custom lingual orthodontic appliance for a Class II high-angle malocclusion, anterior open bite, incisor biprotrusion and crossbite, unilateral second molar scissor bite and dysfunctional tongue thrust. To achieve a counterclockwise rotation of the mandible, implant anchorage was used to control the vertical height. To complete the compensatory therapy, four first premolars were removed. As well as ensuring aesthetics over the 20-month treatment period, the treatment also established a Class I molar relationship, normal overbite and overjet, and improved the facial profile. After a five-year follow-up, the treatment results remained stable.

Convolutional neural network-assisted diagnosis of midpalatal suture maturation stage in cone-beam computed tomography.

OBJECTIVES: The selection of treatment for maxillary expansion is closely related to the calcification degree of the midpalatal suture. A classification method for individual assessment of the morphology of midpalatal suture in cone-beam computed tomography (CBCT) is useful for evaluating the calcification degree. Currently, convolutional neural networks (CNNs) have been introduced into the field of oral and maxillofacial imaging diagnosis. This study validated the ability of CNN models in assessing the maturation stage of the midpalatal suture. METHODS: The existing CNN model ResNet50 was trained to locate the CBCT transverse plane which contained a complete midpalatal suture. ResNet18, ResNet50, RessNet101, Inception-v3, and Efficientnetv2-s models were trained to evaluate the midpalatal suture maturation stage. Multi-class classification metrics, accuracy, recall, precision, F1-score, and area under the curve values from the receiver operating characteristic curve were used to evaluate the performance of the models, and gradient-weighted class activation map technology was utilised to visualise five midpalatal suture maturation stages for each model. RESULTS: Resnet50 demonstrated an accuracy of 99.74 % in identifying the transverse plane that contained the complete midpalatal suture. The highest accuracies achieved on the two-stage, three-stage, and five-stage maturation classification tests were 95.15, 88.06, and 75.37 %, all of which exceeded the average accuracy of three experienced orthodontists. CONCLUSIONS: The CNN model can locate the plane of the midpalatal suture in CBCT images and can assist clinicians in assessing the maturation stage of the midpalatal suture to select the means of maxillary expansion. CLINICAL SIGNIFICANCE: The application of artificial intelligence on CBCT midpalatal suture plane localisation and maturation stage evaluation enhances diagnostic and treatment efficiency and accuracy of individual assessment of midpalatal suture calcification degree. Additionally, it assists the clinical palatal expansion technique in achieving ideal results.

Calvaria defect regeneration via human periodontal ligament stem cells and prevascularized scaffolds in athymic rats.

BACKGROUND: Vascularization plays an important role in dental and craniofacial regenerations. Human periodontal ligament stem cells (hPDLSCs) are a promising cell source and, when co-cultured with human umbilical vein endothelial cells (hUVECs), could promote vascularization. The objectives of this study were to develop a novel prevascularized hPDLSC-hUVEC-calcium phosphate construct, and investigate the osteogenic and angiogenic efficacy of this construct with human platelet lysate (hPL) in cranial defects in rats for the first time. METHODS: hPDLSCs and hUVECs were co-cultured on calcium phosphate cement (CPC) scaffolds with hPL. Cell proliferation, angiogenic gene expression, angiogenesis, alkaline phosphatase activity, and cell-synthesized minerals were determined. Bone and vascular regenerations were investigated in rat critical-sized cranial defects in vivo. RESULTS: hPDLSC-hUVEC-CPC-hPL group had 2-fold greater angiogenic expressions and cell-synthesized mineral synthesis than hPDLSC-hUVEC-CPC group (p < 0.05). Microcapillary-like structures were formed on scaffolds in vitro. hPDLSC-hUVEC-CPC-hPL group had more vessels than hPDLSC-hUVEC-CPC group (p < 0.05). In cranial defects in rats, hPDLSC-hUVEC-CPC-hPL group regenerated new bone amount that was 2.1 folds and 4.0 folds, respectively, that of hPDLSC-hUVEC-CPC group and CPC control (p < 0.05). New blood vessel density of hPDLSC-hUVEC-CPC-hPL group was 2 folds and 7.9 folds, respectively, that of hPDLSC-hUVEC-CPC group and CPC control (p < 0.05). CONCLUSION: The hPL pre-culture method is promising to enhance bone regeneration via prevascularized CPC. Novel hPDLSC-hUVEC-CPC-hPL prevascularized construct increased new bone formation and blood vessel density by 4-8 folds over CPC control. CLINICAL SIGNIFICANCE: Novel hPDLSC-hUVEC-hPL-CPC prevascularized construct greatly increased bone and vascular regeneration in vivo and hence is promising for a wide range of craniofacial applications.

LncRNA MALAT1 promotes osteogenic differentiation through the miR-93-5p/SMAD5 axis.

OBJECTIVES: Promoting the osteogenic differentiation of periodontal ligament stem cells (PDLSCs) is a way to regenerate periodontal bone. This study aimed to determine whether lncRNA MALAT1 promotes the osteogenic differentiation of human PDLSCs in vitro. MATERIALS AND METHODS: Human PDLSCs were extracted from the human periodontal ligament, and after osteogenic differentiation was induced using osteogenic medium, the human PDLSCs were transfected with siRNA-MALAT1, miR-93-5p mimics, and miR-93-5p inhibitors. The expression of osteogenesis-related genes was assessed by RT-qPCR and western blotting, alkaline phosphatase (ALP) activity was assessed by ALP activity assay, and the formation of mineralized nodules was assessed by alizarin red S (ARS) staining. RNA immunoprecipitation (RIP) and luciferase assays were performed to assess the binding of MALAT1, miR-93-5p, and SMAD5. RESULTS: The expression of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was upregulated, while that of miR-93-5p was downregulated after PDLSC osteogenic differentiation. Knockdown of MALAT1 inhibited the osteogenic differentiation of PDLSCs, and MALAT1 expression negatively correlated with miR-93-5p expression. miR-93-5p inhibited the osteogenic differentiation of human PDLSCs by specifically binding to SMAD5. CONCLUSION: MALAT1 regulates human PDLSC differentiation by regulating the miR-93-5p/SMAD5 axis.

Injectable periodontal ligament stem cell-metformin-calcium phosphate scaffold for bone regeneration and vascularization in rats.

OBJECTIVES: Injectable and self-setting calcium phosphate cement scaffold (CPC) capable of encapsulating and delivering stem cells and bioactive agents would be highly beneficial for dental and craniofacial repairs. The objectives of this study were to: (1) develop a novel injectable CPC scaffold encapsulating human periodontal ligament stem cells (hPDLSCs) and metformin (Met) for bone engineering; (2) test bone regeneration efficacy in vitro and in vivo. METHODS: hPDLSCs were encapsulated in degradable alginate fibers, which were then mixed into CPC paste. Five groups were tested: (1) CPC control; (2) CPC + hPDLSC-fibers + 0% Met (CPC + hPDLSCs + 0%Met); (3) CPC + hPDLSC-fibers + 0.1% Met (CPC + hPDLSCs + 0.1%Met); (4) CPC + hPDLSC-fibers + 0.2% Met (CPC + hPDLSCs + 0.2%Met); (5) CPC + hPDLSC-fibers + 0.4% Met (CPC + hPDLSCs + 0.4%Met). The injectability, mechanical properties, metformin release, and hPDLSC osteogenic differentiation and bone mineral were determined in vitro. A rat cranial defect model was used to evaluate new bone formation. RESULTS: The novel construct had good injectability and physical properties. Alginate fibers degraded in 7 days and released hPDLSCs, with 5-fold increase of proliferation (p＜0.05). The ALP activity and mineral synthesis of hPDLSCs were increased by Met delivery (p＜0.05). Among all groups, CPC+hPDLSCs+ 0.1%Met showed the greatest cell mineralization and osteogenesis, which were 1.5-10 folds those without Met (p＜0.05). Compared to CPC control, CPC+hPDLSCs+ 0.1%Met enhanced bone regeneration in rats by 9 folds, and increased vascularization by 3 folds (p＜0.05). CONCLUSIONS: The novel injectable construct with hPDLSC and Met encapsulation demonstrated excellent efficacy for bone regeneration and vascularization in vivo in an animal model. CPC+hPDLSCs+ 0.1%Met is highly promising for dental and craniofacial applications.

Effect of human periodontal ligament stem cell-derived exosomes on cementoblast activity.

OBJECTIVES: Exosomes derived from stem cells are a potential cell-free tool for tissue regeneration with therapeutic potential. However, its application in cementum repair is unclear. This study aimed to investigate the effect of human periodontal ligament stem cell-derived exosomes on the biological activity of cementoblasts, the main effector cells in cementum synthesis. MATERIALS AND METHODS: OCCM-30 cementoblasts were cultured with various human periodontal ligament stem cell-derived exosome concentrations. OCCM-30 cells proliferation, migration, and cementogenic mineralization were examined, along with the gene and protein expression of factors associated with cementoblastic mineralization. RESULTS: Exosomal promoted the migration, proliferation, and mineralization of OCCM-30 cells. The exosome-treated group significantly increased the expression of cementogenic-related genes and proteins. Furthermore, the expression of p-PI3K and p-AKT was enhanced by exosome administration. Treatment with a PI3K/AKT inhibitor markedly attenuated the gene and protein expression of cementoblastic factors, and this effect was partially reversed by exosome administration. CONCLUSIONS: Human periodontal ligament stem cell-derived exosomes can promote the activity of cementoblasts via the PI3K/AKT signaling pathway, providing a scientific basis for promoting the repair process in orthodontically induced inflammatory root resorption.

CpG ODN/Mangiferin Dual Delivery through Calcium Alginate Hydrogels Inhibits Immune-Mediated Osteoclastogenesis and Promotes Alveolar Bone Regeneration in Mice.

The immune system plays an important role in the skeletal system during bone repair and regeneration. The controlled release of biological factors from the immune system could facilitate and optimize the bone remodeling process through the regulation of the activities of bone cells. This study aimed to determine the effect of the controlled delivery of immunomodulatory biologicals on bone regeneration. Immunostimulatory cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODN) and glucosylxanthone Mangiferin (MAG)-embedded microbeads were incubated with P. gingivalis-challenged splenocytes, or co-cultured with RAW264.7 cells. The effect of CpG ODN/MAG-containing microbeads on bone regeneration was then tested in vivo in a mouse alveolar bone defect model. The results demonstrated that MAG significantly antagonized P. gingivalis proliferation and reduced the live/dead cell ratio. After the addition of CpG ODN + MAG microbeads, anti-inflammatory cytokines IL-10 and IL-4 were upregulated on day 2 but not day 4, whereas pro-inflammatory cytokine IL-1ß responses showed no difference at both timepoints. RANKL production by splenocytes and TRAP+ cell formation of RAW264.7 cells were inhibited by the addition of CpG ODN + MAG microbeads. Alveolar bony defects, filled with CpG ODN + MAG microbeads, showed significantly increased new bone after 4 weeks. In summary, this study evaluated a new hydrogel-based regimen for the local delivery and controlled release of biologicals to repair and regenerate alveolar bony defects. The combined CpG ODN + MAG treatment may promote alveolar bone regeneration through the anti-microbial/anti-inflammatory effects and the inhibition of RANKL-mediated osteoclastogenesis.