Applications of hydrogels in tissue-engineered repairing of temporomandibular joint diseases.

Epidemiological studies reveal that symptoms of temporomandibular joint disorders (TMDs) occur in 60-70% of adults. The inflammatory damage caused by TMDs can easily lead to defects in the articular disc, condylar cartilage, subchondral bone and muscle of the temporomandibular joint (TMJ) and cause pain. Despite the availability of various methods for treating TMDs, few existing treatment schemes can achieve permanent recovery. This necessity drives the search for new approaches. Hydrogels, polymers with high water content, have found widespread use in tissue engineering and regeneration due to their excellent biocompatibility and mechanical properties, which resemble those of human tissues. In the context of TMD therapy, numerous experiments have demonstrated that hydrogels show favorable effects in aspects such as articular disc repair, cartilage regeneration, muscle repair, pain relief, and drug delivery. This review aims to summarize the application of hydrogels in the therapy of TMDs based on recent research findings. It also highlights deficiencies in current hydrogel research related to TMD therapy and outlines the broad potential of hydrogel applications in treating TMJ diseases in the future.

The Host Response to Autogenous, Allogeneic, and Xenogeneic Treated Dentin Matrix/Demineralized Dentin Matrix-Oriented Tissue Regeneration.

Dentin is a bone-like matrix that forms the bulk of the tooth. By fabricating dentin with protocols involving demineralization, sterilization, and preservation, treated dentin matrix (TDM)/demineralized dentin matrix (DDM) could be obtained, which is considered as a useful tool for bone and tooth-tissue regeneration. Non-negligible inflammatory and immune responses are reviewed in this article of autogenous, allogeneic, and xenogeneic TDM/DDM for the first time. Both autogenous and allogeneic TDM/DDM showed good biocompatibility in original and clinical studies, while a few cases reported the observation of inflammatory cells around tissue samples. As for xenogeneic TDM/DDM, multiple immune responses were revealed. Immune cells, including eosinocytes, macrophages, lymphocytes, mutinucleated giant cell, M1/M2 macrophages, and Th1-type CTL responses were involved. To avoid these adverse inflammatory responses caused by TDM/DDM implantation, some of the effective fabricating methods are discussed to reduce host immune responses to TDM/DDM.

Customized planning of the visible maxillary arch width in harmony with interparopia width and smile width for female facial aesthetics.

BACKGROUND: The visible maxillary arch width (VAW) is an important aesthetic-determining feature. To date, there is no well-established methodology to determine the aesthetically optimal VAW in customized treatment planning. METHODS: In this study, the common traits of the dentofacial configuration were investigated in most attractive Asian and Caucasian female smiles. The smiling photo of a subject was digitally modified based on combined variations of VAW, smile width (SW), transverse facial dimensions (TFD), and vertical facial dimensions. These modified photos were assessed for aesthetics. The aesthetically essential parameters were identified, and their mathematic correlations and reference ranges were determined for different vertical facial patterns. Using the obtained results, a mathematic guidance was constructed for customized smile designing. The applicability of this guidance was tested in Asian females. RESULTS: The most attractive Asian and Caucasian female smiles have intraracial and interracial commonalities in the VAW-to-TFD ratios. The interparopia width (IPD) predominated over facial widths in determining well-matched VAW and SW. For optimal smile aesthetics, the VAW and SW were correlated as simulated by the formula 1.92 IPD ≤ VAW + 2.3 SW ≤ 2.17 IPD, plus the VAW-to-IPD ratio within 0.54 to 0.62 and the SW-to-IPD ratio within 0.61 to 0.71, ranges tailored to vertical facial patterns. This constitutes a mathematic guidance for customized planning of the aesthetically optimal VAW. This guidance was preliminarily validated to be applicable to Asian females. CONCLUSIONS: The VAW-to-TFD ratios were essential for Caucasian and Asian female smile aesthetics. The mathematic guidance could serve as a reference for customized smile designs for Asian females.

YAP/TAZ: Molecular pathway and disease therapy.

The Yes-associated protein and its transcriptional coactivator with PDZ-binding motif (YAP/TAZ) are two homologous transcriptional coactivators that lie at the center of a key regulatory network of Hippo, Wnt, GPCR, estrogen, mechanical, and metabolism signaling. YAP/TAZ influences the expressions of downstream genes and proteins as well as enzyme activity in metabolic cycles, cell proliferation, inflammatory factor expression, and the transdifferentiation of fibroblasts into myofibroblasts. YAP/TAZ can also be regulated through epigenetic regulation and posttranslational modifications. Consequently, the regulatory function of these mechanisms implicates YAP/TAZ in the pathogenesis of metabolism-related diseases, atherosclerosis, fibrosis, and the delicate equilibrium between cancer progression and organ regeneration. As such, there arises a pressing need for thorough investigation of YAP/TAZ in clinical settings. In this paper, we aim to elucidate the signaling pathways that regulate YAP/TAZ and explore the mechanisms of YAP/TAZ-induce diseases and their potential therapeutic interventions. Furthermore, we summarize the current clinical studies investigating treatments targeting YAP/TAZ. We also address the limitations of existing research on YAP/TAZ and propose future directions for research. In conclusion, this review aims to provide fresh insights into the signaling mediated by YAP/TAZ and identify potential therapeutic targets to present innovative solutions to overcome the challenges associated with YAP/TAZ.

YAP/TEAD1 and ß-catenin/LEF1 synergistically induce estrogen receptor α to promote osteogenic differentiation of bone marrow stromal cells.

Bone remodeling is vital to the maintenance of bone homeostasis and may lead to destructive skeletal diseases once the balance is disrupted. Crosstalk between Wnt and estrogen receptor (ER) signaling has been proposed in bone remodeling, but the underlying mechanism remains unclear. This study was designed to explore the effect of Wnt-ER signaling during the osteogenic differentiation of bone marrow stromal cells (BMSCs). Rat BMSCs were isolated and identified using flow cytometry and stimulated with Wnt3a. Wnt3a treatment promoted osteogenic differentiation and mineralization of the BMSCs. Meanwhile, Wnt3a enhanced the expression of ERα as well as the canonical Wnt signaling mediator ß-catenin and the alternative Wnt signaling effector Yes-associated protein 1 (YAP1). Interestingly, DNA pulldown assay revealed direct binding of transcriptional enhanced associate domain 1 (TEAD1) and lymphoid enhancer binding factor 1 (LEF1), transcriptional partners of YAP1 and ß-catenin, respectively, to the promoter region of ERα. In addition, inhibition of TEAD1 and LEF1 suppressed Wnt3-promoted BMSC osteogenic differentiation and blocked Wnt3a-induced ERα expression. Furthermore, an in vivo model of femoral bone defect also supported that Wnt3a facilitated bone healing in an ERα-dependent way. Together, we suggest that Wnt3a promotes the osteogenic activity of BMSCs through YAP1 and ß-catenin-dependent activation of ERα, via direct binding of TEAD1 and LEF1 to the ERα promoter.

Orthodontic retreatment need and related self-perceived factors among contemporary college freshmen in China.

Given that an increasing number of patients who received orthodontic treatment during their childhood or adolescence are seeking retreatment in contemporary China, it is of great necessity to comprehensively understand their motivations. A valid and reliable self-designed questionnaire, based on the Index of complexity, outcome and need (ICON), was distributed online to college freshmen who received orthodontic treatment during their childhood or adolescence. After collecting their basic information and orthodontic retreatment needs data from the survey, the participants' general self-perception of front facial appearance, lateral facial appearance and tooth alignment, as well as their self-perceived dental alignment, occlusal status, oral function and psychological status, were assessed. Correlation analysis, Chi-square test, Kruskal-Wallis test and logistic regression were performed. Reliability was evaluated for 20 paired questionnaires, and all questions were found to be reliable (intraclass correlation coefficient, >0.70). Among the 1609 participants with a history of orthodontic treatment, 45.56% were males and 54.44% were females. Their mean age was 18.48 ± 0.91 years. Our results showed that self-perceived front facial appearance, lateral facial profile, tooth alignment, occlusal status, oral function and psychological status were significantly correlated with orthodontic retreatment needs. Both appearance and psychological status affected their self-perceived dental alignment and occlusal status. In conclusion, patients who received orthodontic treatment during their childhood or adolescence in contemporary China seek orthodontic retreatment because they desire better aesthetics of their front facial appearance and tooth alignment, especially the anterior region of the tooth, the lower part of the face and a decent pronunciation. Additionally, psychological concerns should be viewed as an urge, while intraoral factors should be viewed as the foundation during future clinical practice regarding orthodontic retreatment in this age group.

XGBoost-aided prediction of lip prominence based on hard-tissue measurements and demographic characteristics in an Asian population.

INTRODUCTION: Prediction of lip prominence based on hard-tissue measurements could be helpful in orthodontic treatment planning and has been challenging and formidable thus far. METHODS: A machine learning-based cross-sectional study was conducted on 1549 patients. Hard-tissue measurements and demographic information were used as the input features. Seven popular machine learning algorithms were applied to the datasets to predict upper and lower lip prominence. The algorithm that performed the best was selected for the construction of the prediction model. Evaluation of feature importance was conducted using 3 classical methods. RESULTS: Among the 7 algorithms, the XGBoost model performed the best in the prediction of the distances between labrale superius or labrale inferius to the esthetics plane (UL-EP and LL-EP distances), with root mean square error values of 1.25, 1.49 and r2 values of 0.755 and 0.683, respectively. Among the 14 input features, the L1-NB distance contributed the most to the prominences of the upper and lower lips. A lip prominence predictor was developed to facilitate clinical application by deploying the prediction model into a downloadable tool kit. CONCLUSIONS: The XGBoost model performed well with high accuracy and practicability in predicting upper and lower lip prominence. The artificial intelligence-aided predictor could serve as a reference for orthodontic treatment planning.

Orthodontic correction of a skeletal Class II malocclusion with severe gummy smile by total intrusion of the maxillary dentition.

A 22-year-old woman visited the hospital complaining of lip protrusion, crowded teeth, and a gummy smile. The clinical examination showed a convex profile with a hyperdivergent mandible and a severe gummy smile in both anterior and posterior regions. The unstable mandible position was considered during treatment planning, and a targeted mechanic system was carefully designed. Temporary skeletal anchorage devices in the posterior dental region and a transpalatal arch were introduced as anchorage for the intrusion of the entire maxillary dentition and controlled retraction of the anterior teeth. Based on effective and simple mechanisms, we successfully eliminated the severe gummy smile and improved the facial aesthetics with the aid of conventional appliances. This approach provided an alternative option to orthognathic surgery or bulky invasive miniscrews for treatment of skeletal Class II malocclusion with severe gummy smile.

A survey regarding orthodontic treatment among contemporary college freshmen in China.

BACKGROUND: A growing number of Chinese residents are seeking orthodontic treatment. The aim of the study was to investigate rates of orthodontic publicity, orthodontic treatment history and related factors among college freshmen in China, to preliminarily understand the current situation of orthodontic publicity and treatment in China, especially after the 2020s. METHODS: Referred to previous studies, a self-designed online questionnaire of Chinese college freshmen was conducted. The questionnaire was divided into two parts, after collecting basic information, we investigated orthodontic publicity rate and orthodontic treatment history with starting age, relapse phenomenon, satisfaction score and willingness to re-treatment. Factors hindering first-time and second-time treatment were also collected. The statistical analysis was performed using the Chi-square test, t-test, Kruskal-Wallis test and logistic regression analysis. RESULTS: The response rate was 100% and 3308 responses were included. The male to female ratio was 1524:1784 with a mean age of 18.43 years (SD 0.91 years). Statistically significant of economic administrative regions, age, major and orthodontics engagement of relatives or friends were found on prevalence and rate of orthodontic treatment (P < 0.05). Average opinion on orthodontic treatment was "satisfied" and most claimed a phenomenon of relapse (slight relapse: 38.22%, obvious relapse: 23.12%), where age, major and orthodontics engagement of relatives or friends showed statistically significant. Retreatment willingness was correlation with start age and relapse phenomenon. For those who refused first-time treatment, except for good tooth arrangement condition, pain, long-time span, and cost weighted, while for those who refused re-treatment, the fair of discomfort and long-time span ranked at the top. CONCLUSIONS: In contemporary China, the prevalence and rate of orthodontic treatment had been greatly promoted. Earlier age for receiving orthodontic treatment was also discovered. Subjective factors regarding psychology, self-requirement affected the need of orthodontic treatment. Contemporary Chinese college freshmen had a high ability of judging dental alignment, while improve of overall orthodontic care level is still required.

Nonsurgical treatment of a hyperdivergent skeletal Class III patient with mini-screw-assisted mandibular dentition distalization and flattening of the occlusal plane.

Treatment of hyperdivergent skeletal Class III malocclusion is challenging for orthodontists, and orthognathic-orthodontic treatment is usually required. This report presents the successful nonsurgical treatment of a 20-year-old man who had a skeletal Class III malocclusion with anterior open bite, anterior and posterior crossbite, hyperdivergent growth pattern, steep occlusal plane, early loss of three first molars, and an uncommon convex profile with a retruded chin. An orthodontic camouflage treatment plan was chosen based on the etiology and the patient's complaints. Tooth #37 was extracted. Miniscrews were used for uprighting and intruding of the lower molars, distalization of the lower dentition, and flattening of the occlusal plane. After 34 months of active treatment, Class I relationships, proper anterior overjet and overbite, flat occlusal plane, and an esthetic facial profile were achieved. The results demonstrated that the biomechanics involved in the nonsurgical treatment assisted with miniscrews to distalize the mandibular dentition and flatten the occlusal plane while keeping the mandibular plane stable was effective for treating this hyperdivergent skeletal Class III patient with a convex profile and anterior open bite.

Roles and mechanisms of YAP/TAZ in orthodontic tooth movement.

Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are transcriptional coactivators encoded by paratactic homologous genes, shuttle-crossing between cytoplasm and nucleus to regulate the gene expression and cell behavior and standing at the center place of the sophisticated regulatory networking of mechanotransduction. Orthodontic tooth movement (OTM) is a process in which extracellular mechanical stimuli are transformed into intracellular biochemical signals to regulate cellular responses and tissue remodeling. Literature studies have confirmed that YAP/TAZ plays an important role not only in embryonic development, homeostasis and tumorigenesis, but also in mechanical-biochemical signal transduction of periodontal tissues under the mediation of various signal molecules in its upstream and downstream. Herein, we review the advances in the roles and mechanisms of YAP/TAZ in OTM to provide insights for better understanding and further study of the OTM and possible targeted clinical intervention in orthodontic treatment.

Rodent incisor and molar dental follicles show distinct characteristics in tooth eruption.

OBJECTIVE: Rodent incisors and molars show different eruption patterns. Dental follicles and their interaction with dental epithelia play key roles in tooth eruption. However, little is known about the differences between incisor dental follicle (IF) and molar dental follicle (MF) during tooth eruption of rodents. This study aimed to investigate the differences between IF and MF during tooth eruption under induction with cervical-loop cells (CLC) and Hertwig's epithelial root sheath (HERS) cells of rats. MATERIALS AND METHODS: CLC, HERS, IF, MF cells were isolated from 10 postnatal day 7 rats and identified by immunofluorescence staining. CLC or HERS cells-derived conditioned medium (CM) was obtained to induce IF and MF cells. Cell proliferation, mineralization, gene and protein expression related to tooth eruption were detected, and histological analysis was also performed. RESULTS: The osteogenic differentiation and mineralization abilities of IF cells were stronger than those of MF cells. Both CLC and HERS cells-derived CM enhanced these abilities of IF cells, whereas they showed the opposite effect on MF cells. At 7, 10, and 15 d after birth, IF cells expressed more OPG and less RANKL than MF cells. CONCLUSIONS: IF and MF cells present distinct characteristics in tooth eruption, CLC and HERS cells have significant inductive effects on them.

Control of SARS-CoV-2 transmission in orthodontic practice.

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has attracted worldwide concerns because of its high person-to-person infectivity and lethality, and it was labeled as a pandemic as the rapid increase in the number of confirmed patients in most areas around the world became evident. The SARS-CoV-2 is mainly transmitted through respiratory droplets and close contact. There is also evidence of transmission through aerosols and digestive tracts. Because orthodontic treatment involves a large population who need routine return-visits, it was significantly affected and suspended because of the COVID-19 pandemic and the shutdown of the dental clinics and hospitals. Although the spread of COVID-19 has been effectively controlled in China, and many areas have gradually resumed work and classes, orthodontic participants are still under high risks of SARS-CoV-2 infection. This is due to the fact that the asymptomatic carriers of SARS-CoV-2 or patients in the incubation period may cause the cross-infection between orthodontic practitioners and patients. The close proximity between the practitioners and the patients, and the generation of droplets and aerosols that contain saliva and blood during treatment further increase the risks of transmission. In this article, we summarized the preventive strategies for control of SARS-CoV-2 transmission to protect both staff and patients during the orthodontic practice.

Estrogen effects on orthodontic tooth movement and orthodontically-induced root resorption.

Estrogen is an essential regulator of the bone tissue. The remodeling of the alveolar bone and periodontal ligament is the basis of orthodontic tooth movement (OTM). There is a negative coregulation between physiological estrogen levels and the rate of OTM. As a possible inhibitory factor of OTM, estrogen suppresses bone resorption by inhibiting osteoclastic differentiation and restraining osteoclast lifespan though multiple pathways and cytokines, leading to the suppression of the initiation step of bone remodeling. On the other hand, estrogen stimulates osteoblastic differentiation and function. Estrogen receptor-α (ERα) involves in the osteogenic responses to mechanical stimulation, and the ERα expression is regulated positively by the levels of circulatory estrogen. Orthodontically induced root resorption (OIRR) is a common side-effect of orthodontic treatment. Estrogen may have some inhibitory effects on OIRR, but more studies are needed to get an effective conclusion.

Accurate bracket placement using a computer-aided design and computer-aided manufacturing-guided bonding device: An in vivo study.

INTRODUCTION: A protocol was introduced to achieve accurate bracket placement in vivo, which consisted of operative procedures for precise control, and a computer-aided design and computer-aided manufacturing-guided bonding device. To evaluate the accuracy of this protocol, a 3-dimensional assessment was performed. METHODS: Ten consecutive patients were enrolled. Strictly following the protocol, from December 2017 to March 2018, brackets were placed on the teeth of each patient using the device. To evaluate the accuracy, deviations of positions and orientations for bracket placement were measured. Each patient was followed up after 3 months regarding bracket failures. RESULTS: The guided bonding device was used in all cases, and a total of 205 brackets were successfully bonded and evaluated. Except for 15.12% brackets with torque deviation over 2°, the deviations in mesiodistal, buccolingual, vertical, rotation, and angulation were below the clinical acceptable range (0.5 mm in translation or 2° in orientation) for all brackets. In the 3-month follow-up, there was no bracket failure in any patient. CONCLUSION: This protocol transferred the planned bracket position from the digital setup to patient's dentition with generally high positional accuracy.

YAP regulates periodontal ligament cell differentiation into myofibroblast interacted with RhoA/ROCK pathway.

During orthodontic tooth movement (OTM), periodontal ligament cells (PDLCs) receive the mechanical stimuli and transform it into myofibroblasts (Mfbs). Indeed, previous studies have demonstrated that mechanical stimuli can promote the expression of Mfb marker α-smooth muscle actin (α-SMA) in PDLCs. Transforming growth factor ß1 (TGF-ß1), as the target gene of yes-associated protein (YAP), has been proven to be involved in this process. Here, we sought to assess the role of YAP in Mfbs differentiation from PDLCs. The time-course expression of YAP and α-SMA was manifested in OTM model in vivo as well as under tensional stimuli in vitro. Inhibition of RhoA/Rho-associated kinase (ROCK) pathway using Y27632 significantly reduced tension-induced Mfb differentiation and YAP expression. Moreover, overexpression of YAP with lentiviral transfection in PDLCs rescued the repression effect of Mfb differentiation induced by Y27632. These data together suggest a crucial role of YAP in regulating tension-induced Mfb differentiation from PDLC interacted with RhoA/ROCK pathway.

Are Hertwig's epithelial root sheath cells necessary for periodontal formation by dental follicle cells?

OBJECTIVE: The role of Hertwig's epithelial root sheath (HERS) cells in periodontal formation has been controversial. This study aimed to further clarify whether HERS cells participate in formation of the periodontium, and the necessity of HERS cells in differentiation of dental follicle cells (DFCs) for periodontal regeneration. DESIGN: HERS cells and DFCs were isolated and identified from post-natal 7-day Sprauge-Dawley rats. In vitro, direct co-culture of HERS cells and DFCs as well as the individual culture of HERS and DFCs were performed and followed by alizarin red staining and the quantitative real-time polymerase chain reaction analysis. For in vivo evaluation, the inactivated dentin matrix (iTDM) was fabricated. HERS cells and DFCs were seeded in combination or alone on iTDM and then transplanted into the rat omentum. Scanning electron microscope and further histological analysis were carried out. RESULTS: In vitro, mineral-like nodules were found in the culture of HERS cells alone or HERS + DFCs either by alizarin red staining or scanning electronic microscope. The mineralization and fiber-forming relevant mRNA expressions, such as bone sialoprotein, osteopontin, collagen I and collagen III in HERS + DFCs were significantly higher than that of the HERS or DFCs alone group. After transplantation in vivo, cementum and periodontal ligament-like tissues were formed in groups of HERS + DFCs and HERS alone, while no evident hard tissues and attached fibers were found in DFCs alone. CONCLUSIONS: Hertwig's epithelial root sheath cells directly participate in the formation of the periodontium, and they are essential for the differentiation of dental follicle cells to form periodontal structures. The combination use of Hertwig's epithelial root sheath cells and dental follicle cells is a promising approach for periodontal regeneration.

Comparative study on differentiation of cervical-loop cells and Hertwig's epithelial root sheath cells under the induction of dental follicle cells in rat.

Cervical loop cells (CLC) and Hertwig's epithelial root sheath (HERS) cells are believed to play critical roles in distinct developmental patterns between rodent incisors and molars, respectively. However, the differences in differentiation between CLC and HERS cells, and their response to inductions from dental follicle cells, remain largely unknown. In present study, CLC and HERS cells, as well as incisor dental follicle (IF) cells and molar dental follicle (MF) cells were isolated from post-natal 7-day rats. IF and MF cell derived conditioned medium (CM) was obtained for induction of CLC and HERS cells. In vitro experiments, we found that, under the induction of dental follicle cell derived CM, CLC cells maintained the epithelial polygonal-shapes and formed massive minerals, while part of HERS cells underwent shape transformation and generated granular minerals. CLC cells expressed higher enamel-forming and mineralization related genes, while HERS cells showed opposite expression patterns of BMP2, BMP4, AMBN and AMGN. In vivo, CLC cells generated enamel-like tissues while HERS cells formed cementum-periodontal ligament-like structures. Taken together, CLC and HERS cells present distinct differentiation patterns under the inductions from dental follicle cells.