Objective:This study investigates the biomechanical effects of different orthodontic movement patterns on the alveolar bone in the adjacent edentulous region through finite element analysis (FEA) of maxillary central incisor displacement mechanisms. Methods:A three-dimensional FEA model was constructed comprising the maxilla, upper dentition (with exclusion of the right maxillary central incisor), periodontal ligament (PDL), fixed orthodontic appliance bracket, and archwire system. The initial displacement characteristics and stress distribution patterns of the maxillary left central incisor (tooth 21) and the surrounding alveolar bone were quantitatively analyzed using ANSYS software. Results:Under an intrusion force approximately four times the lingual reactionary force, the maxillary central incisor underwent pure axial intrusion without labial or lingual tipping. Adjacent tooth movement had minimal mechanical impact on the edentulous alveolar bone (<0.5% strain). The resistance center of the incisor was identified 0.43 times the root length apical to the alveolar ridge crest, necessitating precise force vector alignment to achieve bodily movement without rotational displacement or alveolar bone remodeling. For incisal tipping correction, a horizontal tensile force (F) combined with an archwire-bracket-induced moment (M) allows controlled tipping via modulation of the M/F ratio. However, excessive force risks pathological root resorption and alveolar bone atrophy in edentulous regions. Conclusion:Bodily movement of the central incisor, when guided through the resistance center, does not significantly remodel the edentulous alveolar bone. Moreover, effective tipping correction requires precise M/F ratio control to optimize movement efficiency while minimizing iatrogenic risks. Deviations from optimal force parameters substantially increase the likelihood of alveolar bone atrophy.

Angiogenesis involves the activation of endothelial cells (ECs). Low-intensity pulsed ultrasound (LIPUS), which delivers ultrasound waves at a low intensity, can induce the angiogenic potential of ECs. However, the underlying cellular mechanisms remain to be elucidated. In this study, the LIPUS parameters were 1.5 MHz pulsed frequency, 200 us pulse duration, 1.0 kHz repetition rate, and 30 mW/cm2 energy intensity. First, we evaluated the effects of LIPUS on the proliferation and angiogenic differentiation of the EC line EA.hy926. The results showed that LIPUS could induce cell proliferation, promote migration, and increase mRNA level in KDR and CD144. Also, the mRNA level and secretion of VEGF were enhanced. We then investigated the role of the AKT signaling pathway in this process. We observed that the expression of p-AKT was upregulated which means that the AKT signaling pathway could be activated by LIPUS, while inhibitor LY294002 of the AKT signaling pathway effectively blocked LIPUS-induced angiogenesis. Finally, we applied confocal Raman microscopy to track biomolecular changes in cells after LIPUS treatment. Spectral analysis showed DNA methylation changes. An Infinium Methylation assay suggested that 399 sites were significantly different. After KEGG enrichment analysis, we found seven genes (IRS1, GNG7, COL4A1, FOXO3, COL4A2, CDK4 and EGF) which were closely related to AKT signaling pathway. We verified that AKT signaling pathway inhibition partially blocked LIPUS-induced DNA methylation changes. Our study demonstrated that LIPUS could promote the proliferation and angiogenic differentiation of ECs via the AKT signaling pathway. LIPUS could also alter DNA methylation of ECs via the activation of AKT signal.

INTRODUCTION:This study evaluated arch form accuracy with or without premolar extraction in customized fixed labial orthodontic appliance treatment.METHODS:Setup and posttreatment digital models of 27 samples (15 extractions and 12 nonextractions) were selected and superimposed by best-fit surface-based registration in both the maxilla and the mandible. The facial axis points were identified and converted into Cartesian coordinates. A sixth-order polynomial equation was used to fit dental arches. Arch discrepancies (the mean distance between 2 arch forms) and similarities were compared between extraction and nonextraction groups, maxilla and mandible, and anterior and posterior arches.RESULTS:The arch discrepancy between extraction and nonextraction groups showed no statistically significant difference, but a statistically significant difference in arch similarity was found in the mandible. There were statistically significant differences between anterior and posterior arch discrepancies in the extraction (mandible) and the nonextraction (maxilla and mandible) groups. However, no statistically significant correlation was shown between anterior and posterior arch discrepancies. The arch similarities were 96.18% and 97.38% in the maxilla and 96.01% and 97.49% in the mandible between extraction and nonextraction groups. Arch form discrepancies and similarities showed a moderate correlation but no statistically significant differences between the maxilla and the mandible.CONCLUSIONS:In customized fixed labial orthodontic appliance treatment, arch form setup can be accurately achieved with and without premolar extraction. Anterior arch form acquires fewer discrepancies than the posterior arch, and overcorrection should be added to the end of the customized archwire to reduce posterior arch discrepancies. The discrepancy of the maxillary and mandibular arches is interrelated, and adjustments should be made on both maxillary and mandibular archwires to correct single-jaw transverse malposition.

•The dentoalveolar protrusion was treated with customized lingual appliances.•Digitally designed templates were used for periodontal surgery.•Lingual dehiscence would recover at an early stage of retention.

BACKGROUND:The aim of this study was to evaluate anterior teeth movement with different archwire planes and archwire sizes during space closure with and without miniscrew in sliding mechanics. METHODS:A 3D finite element method was applied to simulate anterior teeth retraction with and without miniscrew and power arm. Initial displacements and pressure stresses of periodontal tissue in anterior teeth were calculated after the teeth were applied with retraction forces with different archwire planes and archwire sizes. RESULTS:High archwire plane showed better torque control of anterior teeth in both sliding mechanics. With intramaxillary retraction, anterior teeth showed lingual tipping and extrusion movement, whereas larger-size archwires did not reduce it. In miniscrew sliding mechanics, anterior teeth showed labial tipping and intrusion movement. Compared with intramaxillary retraction, the retraction force produced less pressure stress on periodontal tissue in miniscrew sliding mechanics with long power arm. CONCLUSIONS:Higher archwire plane is conducive to anterior teeth torque control. In order to achieve the bodily movement of the anterior teeth during space closure, it is more important to choose the appropriate method (miniscrew sliding mechanics with long power arm), instead of increasing the size of the archwire.

Stimuli-responsive biomaterials have attracted more attention in drug delivery area as controlled release with physiologically relevant temporal and spatial context. Teriparatide is used for osteoporosis treatment by systemic administration. Recently, the extending utilization of local biomimetic delivery to repair bone defect provides numerous advantages, for its anabolic effect, maintaining local higher concentration and avoiding side effects. In the present study, we firstly design and propose the concept of Teriparatide time and dose manner on bone marrow mesenchymal stem cells derived from ovariectomized rats (OVX-BMSCs). And the near-infrared (NIR) light responsive, reduced graphene oxide loaded chitosan hydrogel (CS/rGO) films are the fabricated by electrodeposition. The local delivery of Teriparatide, which mimic pulsatile secretion in physiological conditions, is achieved by photothermal conversion. And the osteogenesis and angiogenesis of this delivery system are evaluated in calvarial defect osteoporotic models. And the optimal time and dose manner of Teriparatide is around 1 h*24*10(-9) mol L-1(M)/day to 2 h*12*10(-9) M/day by evaluating the osteogenic activity on OVX-BMSCs. The micro-computed tomography (Micro-CT) and histological analysis illustrate that NIR light-responsive CS/rGO films achieve a favorable effect for bone regeneration through biomimetic delivery of Teriparatide. Moreover, higher density of blood vessels is observed between the newly formed bone and in the center of defect region. Our research combines physiological pulsatile secretion of Teriparatide with the stimuli-responsive effect of the biomaterial, which provides a novel strategy to improve osteoporotic bone regeneration.

Background: Few studies have been reported regarding the accuracy of 3D-printed models for orthodontic applications. The aim of this study was to assess the accuracy of 3D-printed dental models of different tooth surfaces. Methods： Thirty maxillary dental models were produced by means of a stereolithography-based 3D printer. Each printed model was digitally scanned and compared with the oral-scanned STL file via superimposition analysis, with a colour map used to assess the accuracy of different surfaces of anterior and posterior teeth. Results: Statistically significant differences were found in the average deviations of different tooth surfaces. The mean average absolute deviations of the occlusal surfaces of posterior teeth were greater than those of other surfaces. Percentages of points beyond the upper and lower limits of different tooth surfaces displayed the same results. Conclusions: The occlusal surfaces of posterior teeth on 3D-printed dental models show greater deviations than those of other regions, especially in pits and fissures.

Angiogenesis involves the activation of endothelial cells followed by capillary formation. Leptin, the protein product of the ob gene, can induce the angiogenic potential of endothelial cells. However, the underlying cellular mechanism still remains to be elicited. We firstly evaluated the in vitro effects of leptin on proliferation and angiogenic differentiation of endothelial cell line EA.hy926. Leptin was found to potently induced cell proliferation, expression of angiogenic gene, migration and tube formation. Then we investigated the roles of the Akt and Wnt signaling pathways in the aforementioned processes. It showed that Akt and Wnt signaling pathways could be activated by leptin, while inhibition of the Akt and Wnt signaling pathways by siRNAs effectively blocked the leptin-induced angiogenesis. Finally, we used electrospinning to fabricated leptin-immobilized linear poly(L-lactide-co-caprolactone) (PLCL)-leptin. The in vivo vessel formation of PLCL-leptin was evaluated using subcutaneous implants in Sprague-Dawley rats. The histological and immunofluorescence revealed that cell infiltration with PLCL-leptin was much more significant than that with the control PLCL group. More importantly, the number of laminin(+) vessels and CD31(+) cells in PLCL-leptin grafts was significantly higher than in control grafts. The study demonstrated that it is via Akt and Wnt signaling pathways that leptin promotes the proliferation and angiogenic differentiation of endothelial cells and the capacity of endogenous tissue regeneration makes the novel leptin-conjugated PLCL promising materials for grafts.

Patients with cartilage damage have various discomforts, including pain, clicks, deformities, and dysfunction. Chondrocytes are a crucial component of cartilage restoration; however, their limited proliferative ability and degenerative specificity dramatically reduce their effectiveness. In the present study, the effects of leptin on chondrocyte proliferation, chondrogenic and secretion marker gene expression, and chondrocyte cartilage matrix component secretion were evaluated in vitro. The roles of the mitogen-activated protein kinase (MAPK) and protein kinase B (AKT) signaling pathways in these processes were also investigated. More importantly, a leptin sustained release system was developed using a hydrogel with calcium alginate microspheres and was transplanted into cartilage defects in rabbit femurs to analyze the effect of leptin on promoting cartilage restoration. The results showed that leptin promoted cell proliferation and chondrocyte gene expression in a dose-dependent manner, and a concentration of 100 ng/mL leptin had the greatest effect. The activation of the P38 and AKT signaling pathways might be responsible for these effects. An improved in vivo restoration outcome was observed in the leptin sustained release group compared with the control group. These results suggest that leptin could be used as a suitable drug for cartilage restoration.

The chemical signals of biomaterials could influence bone marrow stromal cells (BMSCs)-endothelial cells (ECs) communication during vascularized bone regeneration. However, the underlying mechanisms still remain unknown. Exosomes, a series of extracellular vesicles, have recently emerged as potential paracrine mediators in cell-cell communication. However, whether exosomes and exosomal microRNAs (miRNAs) are involved in the chemical signals of biomaterials-modulated BMSCs-ECs communication are unknown. Hence, in the present study, a model Li-incorporated bioactive glass ceramic (Li-BGC) was applied to explore the chemical signals of biomaterials mediated cell-cell communication between BMSCs and ECs. Our results showed that Li-BGC directly promoted the pro-angiogenic capability of HUVECs in vitro and new blood vessel ingrowth in vivo. Moreover, Li-BGC activated Wnt/β-catenin, AKT and NF-κB signaling pathways, while AKT signaling pathway might function as the upstream of Wnt/β-catenin and NF-κB signaling pathways. More importantly, Li-BGC further facilitated the pro-angiogenic capacity of HUVECs by eliciting the expression of exosomal pro-angiogenic miR-130a in BMSCs-derived exosomes, which subsequently leading to the downregulation of PTEN protein and activation of AKT pathway, ultimately resulting in the elevated proliferation, migration and tube formation of endothelial cells, as well as the upregulated expression of pro-angiogenic genes. Our findings may provide new insights into the regulatory roles of the chemical signals of biomaterials in BMSCs-ECs communication via stimulating exosomal miR-130a secretion and PTEN/AKT signaling pathway in the angiogenic process of bone remodelling.

The cranial base is the foundation of the craniofacial structure, and any interruption of the cranial base can lead to facial deformity. The cranial base develops from two synchondroses via endochondral ossification. Chondrogenesis is an important step in endochondral ossification. A disintegrin and metalloprotease (ADAM) 10 participates in the Notch1 signalling pathway, which has been reported to regulate chondrogenesis via a SOX9-dependent mechanism. However, little is known about the function of ADAM10 in chondrogenesis. In this study, adam10-conditional-knockout (cKO) mice exhibited sharper naso-labial angles and flatter skulls than wild-type (WT) mice. In the sagittal plane, SOX9 was more widespread in the cranial base in Adam10-cKO mice than in WT mice. For in vitro experiments, we used the ATDC5 cell line as a model to investigate the role of ADAM10 in chondrogenesis. Plasmid 129 was designed to decrease the expression of Adam10; the resulting downregulation of Adam10 reduced the production of N1ICD. Plasmid 129 increased the expression of SOX9 under chondrogenic induction, and this increase could be inhibited by transfection with exogenous N1ICD. Collectively, these results show that ADAM10 participates in chondrogenesis by negatively regulating SOX9 expression in an N1ICDdependent manner during cranial base development.

The cranial base is the foundation of the craniofacial structure, and any interruption of the cranial base can lead to facial deformity. The cranial base develops from two synchondroses via endochondral ossification. Chondrogenesis is an important step in endochondral ossification. A disintegrin and metalloprotease (ADAM) 10 participates in the Notch1 signalling pathway, which has been reported to regulate chondrogenesis via a SOX9-dependent mechanism. However, little is known about the function of ADAM10 in chondrogenesis. In this study, adam10-conditional-knockout (cKO) mice exhibited sharper naso-labial angles and flatter skulls than wild-type (WT) mice. In the sagittal plane, SOX9 was more widespread in the cranial base in Adam10-cKO mice than in WT mice. For in vitro experiments, we used the ATDC5 cell line as a model to investigate the role of ADAM10 in chondrogenesis. Plasmid 129 was designed to decrease the expression of Adam10; the resulting downregulation of Adam10 reduced the production of N1ICD. Plasmid 129 increased the expression of SOX9 under chondrogenic induction, and this increase could be inhibited by transfection with exogenous N1ICD. Collectively, these results show that ADAM10 participates in chondrogenesis by negatively regulating SOX9 expression in an N1ICD-dependent manner during cranial base development.