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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Smart Dental Materials Intelligently Responding to Oral pH to Combat Caries: A Literature Review.

Smart dental materials are designed to intelligently respond to physiological changes and local environmental stimuli to protect the teeth and promote oral health. Dental plaque, or biofilms, can substantially reduce the local pH, causing demineralization that can then progress to tooth caries. Progress has been made recently in developing smart dental materials that possess antibacterial and remineralizing capabilities in response to local oral pH in order to suppress caries, promote mineralization, and protect tooth structures. This article reviews cutting-edge research on smart dental materials, their novel microstructural and chemical designs, physical and biological properties, antibiofilm and remineralizing capabilities, and mechanisms of being smart to respond to pH. In addition, this article discusses exciting and new developments, methods to further improve the smart materials, and potential clinical applications.

Osteogenic Differentiation Effect of Human Periodontal Ligament Stem-Cell Initial Cell Density on Autologous Cells and Human Bone Marrow Stromal Cells.

Stem cells have differentiation and regulation functions. Here, we discussed the impact of cell culture density on stem cell proliferation, osteoblastogenesis, and regulation. To discuss the effect of the initial culture density of human periodontal ligament stem cells (hPDLSCs) on the osteogenic differentiation of autologous cells, we found that the hPDLSC proliferation rate decreased with an increase in the initial plating density (0.5-8 × 104 cells/cm2) for the 48 h culture cycle. After hPDLSCs induced osteogenic differentiation for 14 days with different initial cell culture densities, the expression of osteoprotegerin (OPG) and runt-related transcription factor 2(RUNX2) and the OPG/ Receptor Activator of Nuclear Factor-κ B Ligand (RANKL) ratio were the highest in the hPDLSCs initially plated at a density of 2 × 104 cells/cm2, and the average cell calcium concentration was also the highest. To study hPDLSCs regulating the osteoblastic differentiation of other cells, we used 50 µg/mL of secreted exosomes derived from hPDLSCs cultured using different initial cell densities to induce human bone marrow stromal cell (hBMSC) osteogenesis. After 14 days, the results indicated that the gene expression of OPG, Osteocalcin(OCN,)RUNX2, and osterix and the OPG/RANKL ratio were the highest in the 2 × 104 cells/cm2 initial cell density group, and the average calcium concentration was also the highest. This provides a new idea for the clinical application of stem cell osteogenesis.

Influence of resin modified glass ionomer cement incorporating protein-repellent and antimicrobial agents on supragingival microbiome around brackets: an in-vivo split-mouth 3-month study.

Objective: To explore the influence of resin modified glass ionomer cement (RMGIC) adhesives containing protein-repellent and quaternary ammonium salt agents on supragingival microbiome, enamel and gingival health around brackets. Materials and Methods: Ten patients (21.4 ± 3.5 years) about to receive fixed orthodontics were enrolled in this study. Unilateral upper teeth bonded with RMGIC incorporating 2-Methacryloyloxyethyl phosphorylcholine (MPC) and Dimethylaminohexadecyl methacrylate (DMAHDM) were regarded as experimental group (RMD), while contralateral upper teeth bonded with RMGIC were control group (RMGIC), using a split-mouth design. Supragingival plaque was collected from both groups before treatment (T0), and at 1 month (T1) and 3 months (T2) of treatment. High-throughput sequencing was performed targeting v3-v4 of 16S rRNA gene. Streptococcus mutans and Fusobacterium nucleatum quantification was done by qPCR analysis. Bracket failures, enamel decalcification index (EDI), DIAGNODent scores (Dd), plaque index (PI) and gingival index (GI) were monitored at indicated time points. Results: Within 3 months, alpha and beta diversity of supragingival plaque had no difference between RMGIC and RMD groups. From T0 to T2, the relative abundance of Streptococcus depleted in RMD but remained steady in RMGIC group. Streptococcus, Prevotella, and Fusobacterium became depleted in RMD, Haemophilus and Capnocytophaga became depleted in RMGIC group but Prevotella enriched. Quantification of Fusbacterium nucleatum and Streptococcus mutans showed significant difference between RMGIC and RMD groups at T2. Teeth bonded with RMD had significant lower plaque index (PI) and DIAGNODent (Dd) score at T2, compared with teeth bonded with RMGIC (p < 0.05). No difference in bracket failure rate was examined between both groups (p > 0.05). Conclusion: By incorporating MPC and DMAHDM into RMGIC, the material could affect the supragingival microbial composition, inhibit the progress of plaque accumulation as well as the key pathogens S. mutans and F. nucleatum in the early stage of orthodontic treatment.

Candida albicans enriched in orthodontic derived white spot lesions and shaped focal supragingival bacteriome.

White spot lesions (WSLs) are common enamel infectious diseases in fixed orthodontic treatment, which might attribute to the dysbiosis of oral microbiome. However, the correlation of Candida albicans with oral bacteriome in WSLs still remains unrevealed. This study investigated the carriage of C. albicans and how it shaped the bacterial community in disease or healthy supragingival plaque, to explore the potential role of interkingdom interaction in orthodontic WSLs. In this study, 31 patients with WSLs (WSLs) and 23 healthy patients (Health) undergoing fixed orthodontic treatment were enrolled. The supragingival microbiota in both groups were determined using 16S rRNA gene sequencing. Colonization and abundance of C. albicans in the plaque were determined via culture-dependent and -independent methods. Among WSLs patients, the correlation of C. albicans and bacteriome was analyzed under QIIME2-based bioinformatics and Spearman's correlation coefficient. The raw reads were deposited into the NCBI Sequence Read Archive (SRA) database (Accession Number: SRP404186). Significant differences in microbial diversity as well as composition were observed between WSLs and Health groups. Leptotrichia remarkably enriched in the WSLs group, while Neisseria and Cardiobacterium significantly enriched in the Health group. In addition, 45% of WSLs patients were C. albicans carriers but none in patients without WSLs. Among all WSLs patients, beta diversity and microbial composition were distinguished between C. albicans carriers and non-carriers. In C. albicans carriers, Corynebacterium matruchotii and Streptococcus mutans significantly enriched whereas Saccharibacteria_TM7_G-1 significantly depleted. The abundance of C. albicans was positively associated with bacteria such as Streptococcus mutans, while the negative correlation was detected between C. albicans and several bacteria such as Cardiobacterium hominis and Streptococcus sanguinis. Our study elucidated the distinguished supragingival plaque microbiome between orthodontic patients with and without WSLs. C. albicans frequently existed and enriched in orthodontic derived WSLs. The carriage of C. albicans shape plaque bacterial community in demineralized lesions and might play roles in WSLs pathogenesis.

A novel injectable fibromodulin-releasing granular hydrogel for tendon healing and functional recovery.

A crucial component of the musculoskeletal system, the tendon is one of the most commonly injured tissues in the body. In severe cases, the ruptured tendon leads to permanent dysfunction. Although many efforts have been devoted to seeking a safe and efficient treatment for enhancing tendon healing, currently existing treatments have not yet achieved a major clinical improvement. Here, an injectable granular hyaluronic acid (gHA)-hydrogel is engineered to deliver fibromodulin (FMOD)-a bioactive extracellular matrix (ECM) that enhances tenocyte mobility and optimizes the surrounding ECM assembly for tendon healing. The FMOD-releasing granular HA (FMOD/gHA)-hydrogel exhibits unique characteristics that are desired for both patients and health providers, such as permitting a microinvasive application and displaying a burst-to-sustained two-phase release of FMOD, which leads to a prompt FMOD delivery followed by a constant dose-maintaining period. Importantly, the generated FMOD-releasing granular HA hydrogel significantly augmented tendon-healing in a fully-ruptured rat's Achilles tendon model histologically, mechanically, and functionally. Particularly, the breaking strength of the wounded tendon and the gait performance of treated rats returns to the same normal level as the healthy controls. In summary, a novel effective FMOD/gHA-hydrogel is developed in response to the urgent demand for promoting tendon healing.

Osteogenic effect of crocin in human periodontal ligament stem cells via Wnt/ß-catenin signaling.

OBJECTIVES: Crocin is a major class of medicinal components in saffron. This study aimed to determine whether crocin directly promotes the proliferation and osteogenic differentiation of human periodontal ligament stem cells (PDLSCs) in vitro and in vivo. MATERIALS AND METHODS: CCK8 cell proliferation assay, reverse transcription quantitative polymerase chain reaction (RT-qPCR), Western blot analysis and Alizarin Red staining were performed in PDLSCs using crocin as a stimulant. DKK1 was used to selectively inhibit Wnt/ß-catenin signaling, and Western blotting was performed to investigate the underlying mechanism. The PDLSCs were mixed with calcium phosphate cement and implanted into nude mice subcutaneously to study the effect of crocin on PDLSC osteogenic differentiation in vivo. RESULTS: The CCK-8 assay showed that crocin did not promote the proliferation of PDLSCs. Treatment with 400 µM crocin significantly promoted PDLSC mRNA levels of ALP, COL1 and OCN; RUNX2 and BMP2 protein expression; mineralized nodule formation in vitro and in vivo; and ALP activity in tissues in vivo. In addition, crocin significantly promoted the phosphorylation of ß-catenin and cyclin D1. DKK1 inhibits Wnt/ß-catenin activation and partially reverses crocin-mediated promotion of PDLSC osteogenic differentiation. CONCLUSION: Crocin may contribute to the regeneration of periodontal bone tissue.

Low-Cost Antimony Selenosulfide with Tunable Bandgap for Highly Efficient Solar Cells.

About 10% efficient antimony selenosulfide (Sb2 (S,Se)3 ) solar cell is realized by using selenourea as a hydrothermal raw material to prepare absorber layers. However, tailoring the bandgap of hydrothermal-based Sb2 (S,Se)3 film to the ideal bandgap (1.3-1.4 eV) using the selenourea for optimal efficiency is still a challenge. Moreover, the expensive selenourea dramatically increases the fabricating cost. Here, a straightforward one-step hydrothermal method is developed to prepare high-quality Sb2 (S,Se)3 films using a novel precursor sodium selenosulfate as the selenium source. By tuning the Se/(Se+S) ratio in the hydrothermal precursor solution, a series of high-quality Sb2 (S,Se)3 films with reduced density of deep defect states and tunable bandgap from 1.31 to 1.71 eV is successfully prepared. Consequently, the best efficiency of 10.05% with a high current density of 26.01 mA cm-2 is achieved in 1.35 eV Sb2 (S,Se)3 solar cells. Compared with the traditional method using selenourea, the production cost for the Sb2 (S,Se)3  devices is reduced by over 80%. In addition, the device exhibits outstanding stability, maintaining more than 93% of the initial power conversion efficiency after 30 days of exposure in the atmosphere without encapsulation. The present work definitely paves a facile and effective way to develop low-cost and high-efficiency chalcogenide-based photovoltaic devices.