Oxygen-Propelled Dual-Modular Microneedles with Dopamine-Enhanced RNA Delivery for Regulating Each Stage of Diabetic Wounds.

Diabetic wounds are characterized by the disruption and cessation of essential healing stages, which include hemostasis, inflammation, proliferation, and remodeling. However, traditional treatments for diabetic wounds concentrate on individual stages of the healing process. Herein, this study utilizes mask-mediated sequential polymerization and varied cross-linking techniques to develop dual-modular microneedles (MNs) with fast- and slow-module, exhibiting varying degradation rates tailored for the full spectrum of diabetic wound healing. First, MNs incorporating calcium ions and dopamine synergistically promote rapid hemostasis. Second, fast-module physically cross-linked MNs rapidly D-mannose/dopamine-enhanced tripolyphosphate-quaternized chitosan (mDTC) nanoparticles (NPs) loaded with microRNA-147 (miRNA-147) to manage inflammation and oxidative stress in diabetic wounds. Additionally, dopamine in these NPs enhances their internalization and safeguards miRNA-147 from oxidative stress and RNase degradation. Finally, slow-module chemically cross-linked MNs facilitate the continuous release of deferoxamine (DFO) and dopamine, accelerating angiogenesis and tissue regeneration during the proliferation and remodeling stages. Manganese/dopamine-enhanced calcium peroxide NPs within the MNs initiate a blast-like generation of oxygen bubbles, not only enhancing the delivery of miRNA-mDTC NPs and DFO but also alleviating tissue hypoxia. Consequently, dual-modular MNs are instrumental in promoting rapid and complete healing of diabetic wounds through all stages of healing.

Effect of orthodontic treatment with premolar extractions on occlusal planes: A retrospective study.

OBJECTIVE: To figure out whether premolar extractions treatment would influence the cant of the occlusal planes and thus affect dentoskeletal patterns in patients with different types of malocclusions. MATERIALS AND METHODS: A total of 140 post-orthodontic treatment subjects (96 females, 44 males) were included in this study, and their lateral cephalograms and demographic information were collected and analysed. The patients were divided into extraction and non-extraction groups. The ANB, SNA, SNB, Wits, Facial Height Index (FHI), SN-MP, SN-AOP, SN-POP and AOP-POP angle were measured on the cephalograms. Other possible confounding factors were recorded. Data were analysed by univariate analysis, stratified analysis, multivariate analysis, and coefficient analysis. RESULTS: After treatment, the changes in the AOP-SN, POP-SN and AOP-POP angle were statistically different between the extraction and non-extraction groups. The results were consistent in different skeletal malocclusions and extent of crowding according to stratified analysis. After adjusting all confounding factors, the cant of the posterior occlusal plane was flattened further by 2.14 degrees in the extraction group than the non-extraction group after orthodontic treatment, and the AOP-SN and AOP-POP angle would further increase by 1.72 and 3.81 degrees, respectively. Although no significant differences were found between the two groups, the SNA, ANB, and Wits in the extraction group decreased more with increased counterclockwise rotation of the mandible. CONCLUSION: Compared to the non-extraction group, there were more increases in the AOP-SN and AOP-POP angle and more posterior flattening in patients with four premolar extractions despite different types of dentoskeletal malocclusion, which were correlated to the change of variables in sagittal and vertical dimensions such as Wits and FHI.

The Cell-Specific Role of SHP2 in Regulating Bone Homeostasis and Regeneration Niches.

Src homology-2 containing protein tyrosine phosphatase (SHP2), encoded by PTPN11, has been proven to participate in bone-related diseases, such as Noonan syndrome (NS), metachondromatosis and osteoarthritis. However, the mechanisms of SHP2 in bone remodeling and homeostasis maintenance are complex and undemonstrated. The abnormal expression of SHP2 can influence the differentiation and maturation of osteoblasts, osteoclasts and chondrocytes. Meanwhile, SHP2 mutations can act on the immune system, vasculature and nervous system, which in turn affect bone development and remodeling. Signaling pathways regulated by SHP2, such as mitogen-activated protein kinase (MAPK), Indian hedgehog (IHH) and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (AKT), are also involved in the proliferation, differentiation and migration of bone functioning cells. This review summarizes the recent advances of SHP2 on osteogenesis-related cells and niche cells in the bone marrow microenvironment. The phenotypic features of SHP2 conditional knockout mice and underlying mechanisms are discussed. The prospective applications of the current agonists or inhibitors that target SHP2 in bone-related diseases are also described. Full clarification of the role of SHP2 in bone remodeling will shed new light on potential treatment for bone related diseases.

Unlocking the link between temporomandibular disorders and suicide ideation in pre-orthodontic patients: A moderated mediation model of depression and anxiety.

BACKGROUND: Temporomandibular disorders (TMD) are a series of musculoskeletal diseases with high prevalence. A few studies have reported the correlation between TMD and suicide ideation (SI). However, the underlying mechanism of the relationship lacks in-depth exploration. METHODS: A cross-sectional study was conducted among 954 pre-orthodontic patients. TMD assessment was based on the quintessential five TMD symptoms (5Ts) questionnaire. Anxiety, depression and pain catastrophizing was evaluated by Seven-item Generalized Anxiety Disorder Scale (GAD-7), Nine-item Patient Health Questionnaire (PHQ-9), and Pain Catastrophizing Scale (PCS), respectively. Correlational and moderated mediated analysis was preformed to demonstrate the relationship between TMD and SI. RESULTS: In pre-orthodontic patients, 31.87 % reported having TMD symptoms and 6.50 % declared SI during the past two weeks. The SI prevalence was 10.53 % in participants with TMD and 4.62 % in those without TMD. Intra-articular TMD, rather than pain-related TMD were especially related with SI. Individuals with TMD had higher risk to SI (rs = 0.112, adjusted OR = 2.213, p < 0.001). The effect of TMD on SI was fully mediated through depression (ß = 0.445, 95 % CI = [0.326, 0.563]). Anxiety exerted a negative moderating effect on the depression-SI relation (ß = -0.033, 95 % CI = [-0.047, -0.019]). LIMITATIONS: This study was a single-centered and cross-sectional survey. The data collection relied on self-reporting methods. CONCLUSIONS: A positive link between TMD and SI was disclosed. The effect of TMD on SI was fully mediated through depression with anxiety as a negative moderator.

Advances in 3D printing techniques for cartilage regeneration of temporomandibular joint disc and mandibular condyle.

Temporomandibular joint (TMJ) osteoarthritis causes fibrocartilage damage to the TMJ disc and mandibular condyle, resulting in local pain and functional impairment that further reduces patients' quality of life. Tissue engineering offers a potential treatment for fibrocartilage regeneration of the TMJ disc and mandibular condyle. However, the heterogeneous structure of TMJ fibrocartilage tissue poses significant challenges for the fabrication of biomimetic scaffolds. Over the past two decades, some researchers have attempted to adopt three-dimensional (3D) printing techniques to fabricate biomimetic scaffolds for TMJ fibrocartilage regeneration, but publications on such attempts are limited and rarely report satisfactory results, indicating an urgent need for further development. This review outlines several popular 3D printing techniques and the significant elements of tissue-engineered scaffolds: seed cells, scaffold materials, and bioactive factors. Current research progress on 3D-printed scaffolds for fibrocartilage regeneration of the TMJ disc and mandibular condyle is reviewed. The current challenges in TMJ tissue engineering are mentioned along with some emerging tissue-engineering strategies, such as machine learning, stimuli-responsive delivery systems, and extracellular vesicles, which are considered as potential approaches to improve the performance of 3D-printed scaffolds for TMJ fibrocartilage regeneration. This review is expected to inspire the further development of 3D printing techniques for TMJ fibrocartilage regeneration.

Craniofacial Morphology of Temporomandibular Disorder Patients with Different Disc Positions: Stratifying Features Based on Sex and Sagittal Skeletal Pattern.

Disc displacement (DD) appears in the majority of temporomandibular disorder (TMD) patients. The correlation between craniofacial morphology and different disc positions has been underlined, while the craniofacial morphological differences based on sex and sagittal skeletal pattern stratification have been insufficiently studied. In this study, 304 patients with TMD complaints were included and classified into normal position, disc displacement with reduction (DDwR) and disc displacement without reduction (DDwoR) groups according to magnetic resonance imaging. A total of 24 cephalometric measurements, covering the cranial base, vertical relationship, sagittal relationship, mandible position and morphology, and dental relationship, were assessed using lateral cephalograms. A stratified analysis was performed based on the sex and sagittal skeletal pattern. Overall, DD patients had distinctive craniofacial morphological features. The posterior cranial base length and mandibular arc angle were statistically different only in females, while the Y-axis angle, occlusal plane angle and sella nasion point A angle (SNA) might be unique features in males. Skeletal class II had the most statistically different measurements compared to the others. Differences in the Frankfort mandibular incisor angle (FMIA) and saddle angle were especially displayed in skeletal class III patients. The sex and skeletal sagittal pattern could affect the morphological differences in TMD patients with different disc positions.

Association between the severity of hypodontia and the characteristics of craniofacial morphology in a Chinese population: A cross-sectional study.

Objective: To investigate craniofacial differences in individuals with hypodontia and explore the relationship between craniofacial features and the number of congenitally missing teeth. Methods: A cross-sectional study was conducted among 261 Chinese patients (males, 124; females, 137; age, 7-24 years), divided into four groups (without hypodontia: no teeth missing, mild: one or two missing teeth, moderate: three to five missing teeth, severe: six or more missing teeth) according to the number of congenitally missing teeth. Differences in cephalometric measurements among the groups were analyzed. Further, multivariate linear regression and smooth curve fitting were performed to evaluate the relationship between the number of congenitally missing teeth and the cephalometric measurements. Results: In patients with hypodontia, SNA, NA-AP, FH-NA, ANB, Wits, ANS-Me/N-Me, GoGn-SN, UL-EP, and LL-EP significantly decreased, while Pog-NB, AB-NP, N-ANS, and S-Go/N-Me significantly increased. In multivariate linear regression analysis, SNB, Pog-NB, and S-Go/N-Me were positively related to the number of congenitally missing teeth. In contrast, NA-AP, FH-NA, ANB, Wits, N-Me, ANS-Me, ANS-Me/N-Me, GoGn-SN, SGn-FH (Y-axis), UL-EP, and LL-EP were negatively related, with absolute values of regression coefficients ranging from 0.147 to 0.357. Further, NA-AP, Pog-NB, S-Go/N-Me, and GoGn-SN showed the same tendency in both sexes, whereas UL-EP and LL-EP were different. Conclusions: Compared with controls, patients with hypodontia tend toward a Class III skeletal relationship, reduced lower anterior face height, flatter mandibular plane, and more retrusive lips. The number of congenitally missing teeth had a greater effect on certain characteristics of craniofacial morphology in males than in females.

Polydopamine-Mediated Immunomodulatory Patch for Diabetic Periodontal Tissue Regeneration Assisted by Metformin-ZIF System.

An essential challenge in diabetic periodontal regeneration is achieving the transition from a hyperglycemic inflammatory microenvironment to a regenerative one. Here, we describe a polydopamine (PDA)-mediated ultralong silk microfiber (PDA-mSF) and metformin (Met)-loaded zeolitic imidazolate framework (ZIF) incorporated into a silk fibroin/gelatin (SG) patch to promote periodontal soft and hard tissue regeneration by regulating the immunomodulatory microenvironment. The PDA-mSF endows the patch with a reactive oxygen species (ROS)-scavenging ability and anti-inflammatory activity, reducing the inflammatory response by suppressing M1 macrophage polarization. Moreover, PDA improves periodontal ligament reconstruction via its cell affinity. Sustained release of Met from the Met-ZIF system confers the patch with antiaging and immunomodulatory abilities by activating M2 macrophage polarization to secrete osteogenesis-related cytokines, while release of Zn2+ also promotes bone regeneration. Consequently, the Met-ZIF system creates a favorable microenvironment for periodontal tissue regeneration. These features synergistically accelerate diabetic periodontal bone and ligament regeneration. Thus, our findings offer a potential therapeutic strategy for hard and soft tissue regeneration in diabetic periodontitis.

College Students with Oral Habits Exhibit Worse Psychological Status and Temporomandibular-Related Quality of Life: A Correlational Study.

Purpose: To evaluate the relationship between oral habits, psychological status, and temporomandibular-related quality of life among college students. Materials and Methods: An online questionnaire was sent to college students who were willing to participate in this anonymous survey, which contained questions about the demographic characteristics of the participants, the Patient Health Questionnaire for Depression and Anxiety (PHQ-4), the Fonseca Anamnestic Index (FAI), and the Oral Health Impact Profile for temporomandibular disorders (OHIP-TMDs). Results: A total of 505 valid questionnaires were collected from 200 males and 305 females (a mean age of 21.81 ± 2.81 years). The prevalence of oral habits in college students was 58% (294/505). Female gender (odds ratio (OR) 1.786) and having oral habits (OR 1.893) were associated with depression and anxiety. Medical students had significantly less depression and anxiety (OR 0.459) than nonmedical students. The possibility of suffering from temporomandibular disorder (TMDs) as evidenced by the OHIP-TMDs score was associated with female gender (OR 1.989) and having oral habits (OR 3.482). Students with oral habits had higher OHIP-TMDs scores. Conclusion: More than half of the college students surveyed had specific oral habits, with a higher prevalence in women than in men. Having oral habits was related to a worse psychological status, higher risk of TMD, and worse temporomandibular-related quality of life.

Psychological Profiles and Their Relevance with Temporomandibular Disorder Symptoms in Preorthodontic Patients.

Background: Temporomandibular disorders (TMDs) refer to a group of heterogenous musculoskeletal diseases with diverse clinical symptoms and an undetermined aetiology. The psychological profiles were closely related to the onset and treatment outcomes of TMDs. Objective: To examine the relevance between psychological profiles and different symptoms of TMDs in preorthodontic patients. Methods: The study was conducted among 570 preorthodontic patients. TMDs symptoms were recorded by the Diagnostic Criteria for TMD (DC/TMD) symptom questionnaire. The seven-item Generalized Anxiety Disorder Scale (GAD-7), the nine-item Patient Health Questionnaire (PHQ-9), and the Pain Catastrophizing Scale (PCS) were used for the evaluation of anxiety, depression, and pain catastrophizing levels. The relevance of three psychological profiles with TMDs and subtypes was evaluated with Spearman's rank correlation test and logistic regression analysis (P < 0.05). Results: 34.56% of the enrolled preorthodontic patients were diagnosed with TMDs. Scores of GAD-7, PHQ-9, and PCS were significantly higher in the TMDs group than in the non-TMDs group. Participants with anxiety, depression, or high pain catastrophizing had a higher prevalence of both pain-related TMDs symptoms and intra-articular TMDs symptoms. The correlations among pain-related TMDs, intra-articular TMDs, and scores on the psychological scales were significant (P < 0.05). The adjusted logistic regression model revealed that anxiety, depression, and high pain catastrophizing were significant risk factors for TMDs with an odds ratio (OR) of 2.196, 1.741, and 1.601, respectively. Depression was associated with higher pain-related TMDs prevalence (OR = 2.136), while anxiety and depression were associated with higher intra-articular TMDs prevalence (OR = 2.341 and 1.473). Conclusion: Anxiety, depression, and high pain catastrophizing were comorbid psychological conditions of TMDs. Depression was the top risk factor for pain-related TMDs, while anxiety rendered the highest risk for intra-articular TMDs. Inclusion of psychological assessments in preorthodontic evaluation might yield great benefits in TMDs screening.

Nonlinear Relationship between Temporomandibular Joint Disc Displacement Distance and Disc Length: A Magnetic Resonance Imaging Analysis.

Objective: to explore the association between the distance of disc displacement and disc morphology in patients with temporomandibular disorders (TMDs). Methods: a total of 717 joints in 473 subjects were enrolled in this cross-sectional study. The magnetic resonance imaging (MRI) of each patient was evaluated for temporomandibular joint (TMJ) disc morphology classification and position. The distance of the disc displacement and disc length were measured for smoothing spline prediction. A stratified analysis was performed based on the types of disc positions. The disc width and length-width ratio (L/W) were also measured. Descriptive statistics, one-way analysis of variance, smoothing spline analysis, threshold analysis, and two piecewise linear regression were performed to investigate the association between the displacement distance and length of discs. Results: the differences in displacement distance among morphological categories and among different disc positions were statistically significant. Nonlinear relationships were found between distance and length in all subjects. Two turning points of distance (−1.8 mm and 1.7 mm) were found, dividing the curve into three segments. Disc width and L/W were significantly different among discs in the three segments of the curve. The correlation coefficient (ß) for the three segments were as follows: −0.6 [95% confidence interval (CI) = −0.9 to −0.3, p < 0.001], 0.0 (95% CI = −0.1 to 0.0, p = 0.027), and −0.7 (95% CI = −0.8 to −0.7, p < 0.001). Nonlinear relationships were also found between the distance and length in cases with anterior disc displacement (ADD), anterior disc displacement with reduction (ADDWR), and without reduction (ADDWoR). Conclusion: the turning points of the disc displacement distance may be considered as a potential reference value for high-risk disc deformation and ADD. Disc length decreases sharply with anterior disc displacement when the disc displacement distance is over 1.7 mm. Prospective and long-term studies are required to clarify the natural course of the disc at different stages of the regression curve.

Gli1+ Mesenchymal Stem Cells in Bone and Teeth.

Mesenchymal stem cells (MSCs) are remarkable and noteworthy. Identification of markers for MSCs enables the study of their niche in vivo. It has been identified that glioma-associated oncogene 1 positive (Gli1+) cells are mesenchymal stem cells supporting homeostasis and injury repair, especially in the skeletal system and teeth. This review outlines the role of Gli1+ cells as MSC subpopulation in both bones and teeth, suggesting the prospects of Gli1 an + cells in stem cell- based tissue engineering.