Contrast-enhanced computed tomography of retromandibular vein position and course patterns relative to the mandible during sagittal split ramus osteotomy.

Background: Sagittal split ramus osteotomy is an established procedure used in oral and maxillofacial surgery. Major bleeding is representative intraoperative complication involves vessels such as the inferior alveolar, facial, and maxillary arteries and accompanying veins, in particular the retromandibular vein (RMV). We previously described the RMV course patterns using embalmed cadavers. However, owing to the possible influence of formalin fixation and unclear skeletal classification of the jaws, the present study aimed to use contrast-enhanced computed tomography to confirm the RMV in patients with defined jaw deformities. Methods: Twenty patients with orthognathic jaw deformities (40 sides) were included. The RMV and the lateral and posterior views of the mandible were evaluated using contrast-enhanced computed tomography. Course patterns and RMV positions were classified as previously reported. Results: Three patterns were identified in the lateral view. Type A: RMV posterior to the posterior border of the ramus (n=25; 62.5%). Type B: adjoining the posterior border of the ramus (n=12; 30.0%). Type C: anterior to the posterior border of the ramus (n=3; 7.5%). Five course patterns were identified in the posterior view. Pattern I: rectilinear course running medial to the posterior border of the ramus (n=3; 7.5%). Pattern II: diagonal course running medially from immediately posterior to posterior border of the ramus (n=11; 27.5%). Pattern III: rectilinear course running immediately posterior to the posterior border of the ramus (n=12; 30.0%). Pattern IV: diagonal course running from lateral to medial relative to the posterior border of the ramus (n=8; 20.0%). Pattern V: diagonal course running from lateral to immediately posterior relative to the posterior border of the ramus (n=6; 15.0%). In the no-course pattern group, the RMV inferior to the lingula was lateral to its position and superior to that of the lingula. In half of the cases, the left and right sides exhibited different running patterns. We observed no correlation between the skeletal patterns of jaw deformities and the course of the RMV. Conclusions: Type B/Pattern II that runs in a straight line bordering the posterior margin of the ramus requires the most attention during surgery. These findings suggest the possibility of predicting intraoperative bleeding risk.

Enhanced Precision in Genioplasty: A Novel Intraoperative Spatial Repositioning Using Computer-Aided Design and Manufacturing Technology and a Holographic Mixed Reality Application.

Genioplasty is performed for the orthognathic surgical correction of dentofacial deformities. This article reports a safe and accurate method for genioplasty combining a novel three-dimensional (3D) device with mixed reality (MR)-assisted surgery using a registration marker and a head-mounted display. Four types of devices were designed based on the virtual operation: a surgical splint with a connector; an osteotomy device; a repositioning device; and a registration marker. Microsoft HoloLens 2 and Holoeyes MD were used to project holograms created using computed tomography (CT) data onto the surgical field to improve the accuracy of the computer-aided designed and manufactured (CAD/CAM) surgical guides. After making an incision on the oral vestibule, the splint was fitted on the teeth and the osteotomy device was mounted at the junction site, placed directly on the exposed mandible bone surface. Temporary screws were fixed into the screw hole. An ultrasonic cutting instrument was used for the osteotomy. After separating the bone, a repositioning device was connected to the splint junction and bone segment, and repositioning was performed. At the time of repositioning, the registration marker was connected to the splint junction, and mandible repositioning was confirmed three-dimensionally through HoloLens 2 into the position specified in the virtual surgery. The rate of overlay error between the preoperative virtual operation and one-month postoperative CT data within 2 mm was 100%. CAD/CAM combined with MR enabled accurate genioplasty.

Mechanical stress-induced FGF-2 promotes proliferation and consequently induces osteoblast differentiation in mesenchymal stem cells.

Mechanical stimuli serve as crucial regulators of bone mass, promoting bone formation. However, the molecular mechanisms governing how mesenchymal stem cells (MSCs) respond to mechanical cues during their differentiation into osteogenic cells remain elusive. In this study, we found that cyclic stretching enhances MSC proliferation but does not increase the expression of osteoblast-related genes. We further revealed that this proliferative effect is mediated by fibroblast growth factor 2 (FGF-2), synthesized by MSCs in response to mechanical stress. Cell proliferation induced by cyclic stretching was inhibited upon the addition of either U0126, an inhibitor of mitogen-activated protein kinase kinase (MEK), or early growth response 1 (EGR1)-targeting small-hairpin RNA (shRNA), indicating the involvement of the extracellular signal-regulated kinase (ERK)/EGR1 signaling pathway. Osteoblast differentiation, evaluated through ALP activity, osteoblast-related gene expression, and mineralization, was stimulated by recombinant human FGF-2 (rhFGF-2) when applied during the proliferation phase, but not when applied during the differentiation stage alone. Our results suggest that FGF-2 indirectly promotes osteoblast differentiation as a downstream effect of stimulating cell proliferation. For the first time, we demonstrate that cyclic stretching induces MSCs to produce FGF-2, which in turn encourages cell proliferation through an autocrine/paracrine mechanism, consequently leading to osteoblast differentiation.

Relationship between Changes in Condylar Morphology and Masticatory Muscle Volume after Skeletal Class II Surgery.

The treatment of dentofacial deformities generally includes orthognathic surgery in which mandibular condyle changes following surgery are a common cause of relapse. This study investigated the changes in the mandibular condyle and related muscles to identify the factors that affected the changes in the mandibular condyle after orthognathic surgery in skeletal class II patients. This research studied 60 joints in 30 patients with skeletal class II dentofacial deformities who received surgical orthodontic treatment, including bilateral sagittal split ramus osteotomy, and underwent computed tomography before and after orthodontic treatment. The mandibular condyle, masseter, and medial pterygoid muscles were reconstructed and measured in 3D. Condylar positional and morphology changes, masseter and medial pterygoid muscle volume, temporomandibular joint (TMJ) pain, and distal segment movement were analyzed. The study observed that both the masseter and medial pterygoid muscle volumes decreased with statistical significance. The changes in the horizontal direction were positively correlated with the amount of movement. The findings indicated that mandibular condyle changes were significantly affected by the movement of the distal segment, the medial pterygoid muscle volume, and the direction of the distal segment, which influenced the treatment's long-term stability after orthognathic surgery.

Quercetin Reduces the Development of 2,3,7,8-Tetrachlorodibenzo-p-dioxin-Induced Cleft Palate in Mice by Suppressing CYP1A1 via the Aryl Hydrocarbon Receptor.

Quercetin is a flavonoid with a wide range of pharmacological activities, including anticancer, antioxidant, and anti-inflammatory effects. Since it is a nutrient that can be consumed with a regular diet, quercetin has recently garnered interest. Quercetin acts as a phytochemical ligand for the aryl hydrocarbon receptor (AhR). Cleft lip and palate are among the most frequently diagnosed congenital diseases, and exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during pregnancy induces cleft palate via AhR. In this study, we investigated the preventive effect of quercetin intake on the TCDD-induced cleft palate and its mechanism of action. The in vivo results suggest that quercetin intake by pregnant mice can prevent cleft palate in fetal mice. In vitro, the addition of TCDD induced a reduction in cell migration and the proliferation of mouse embryonic palatal mesenchymal cells, which was mitigated by the addition of quercetin. The addition of quercetin did not alter the mRNA expression levels of the AhR repressor but significantly suppressed mRNA expression of CYP1A1. In addition, the binding of AhR to a xenobiotic responsive element was inhibited by quercetin, based on a chemically activated luciferase expression assay. In conclusion, our results suggest that quercetin reduces the development of TCDD-induced cleft palate by inhibiting CYP1A1 through AhR.

Three-Dimensional Evaluation of Pharyngeal Morphology in Bimaxillary Surgery with and without Horseshoe Osteotomy in Skeletal Class III Cases.

Repositioning of the jaw in orthognathic treatment generates changes in the soft tissues of the maxillofacial region, with consequent changes in the airway. The purpose of this study was to determine how type of orthognathic surgical procedure affected the 3-dimensional morphology of the upper airway. Forty patients were divided into the following 2 groups according to the type of surgical procedure used: a horseshoe osteotomy (HS) group (20 patients, comprising 11 men and 9 women; average age 24.3±4.5 years) who underwent bimaxillary surgery; and a LeFort I osteotomy (LF) group (20 patients, comprising 8 men and 12 women; average age 22.5±4.6 years) who also underwent bimaxillary surgery. Cephalometric measurements were taken and 3-dimensional pharyngeal morphology evaluated in each group. The amounts of maxilla rotation, posterior maxilla impaction, and mandibular setback all revealed a significantly larger value in the HS group. Evaluation of pharyngeal volume revealed a significant decrease in the upper pharyngeal segment in the LF group. A significant decrease in the lower pharyngeal segment was observed in both groups. Differences were noted in postoperative pharyngeal morphology between the two groups. The results of this study suggest that HS has less effect on the upper pharyngeal segment, regardless of the amount of posterior maxilla impaction.

Surgical Orthodontic Treatment in Case of Severe High Angle Skeletal Class II Malocclusion and Mandibular Retrusion.

This report describes a patient with severe high angle class II malocclusion and mandibular retrusion in whom surgical orthodontic treatment to prevent an increase in ramus height resulted in a significant improvement in esthetics and long-term stability. The patient was a woman aged 30 years 5 months who presented with the chief complaint of maxillary protrusion. She had a convex facial type, a chin button on lip sealing, and a gummy smile. Cephalometric analysis revealed a normal maxilla anterior-posterior position, but significant mandibular retrusion with pronounced clockwise rotation. The anterior maxillary tooth axis was standard, but labially inclined in the mandible. Based on these findings, the diagnosis was skeletal class II high angle malocclusion and mandibular retrusion. The proposed treatment plan comprised 2-jaw surgery with premolar extraction. Le Fort I osteotomy, in particular, was planned in the maxilla to move the ANS upward by 3.0 mm and the PNS downward by 3.0 mm. Sagittal split ramus osteotomy (SSRO) was planned to adjust the mandible and move the mandible forward by 10.0 mm. To prevent postoperative relapse, the short lingual split method was used in performing the SSRO. The mandible was split to minimize stretching of the median pterygoid muscle. Postoperatively, the ANS, PNS, and pogonion showed movement of 2.0 mm upward, 3.0 mm downward, and 8.0 mm forward, respectively. Additionally, lip closure was now natural, and the gummy smile had markedly improved. At 6 years postoperatively, there has been no change skeletally or dentally. Follow-up is being continued to monitor further progress.

CAGE-seq analysis of osteoblast derived from cleidocranial dysplasia human induced pluripotent stem cells.

Non-coding RNAs (ncRNAs) comprise a major portion of transcripts and serve an essential role in biological processes. Although the importance of major transcriptomes in osteogenesis has been extensively studied, the function of ncRNAs in human osteogenesis remains unclear. Previously, we developed hiPSCs from patients with cleidocranial dysplasia (CCD) caused by runt-related transcription factor 2 (RUNX2) haploinsufficiency. To gain insight into ncRNAs in osteogenesis, we surveyed differential ncRNA expression profiling and promoter differences of RUNX2 using patient-specific iPSCs and cap analysis gene expression (CAGE) technology to define the promoter landscape. Revertant iPSCs (Rev1 iPSCs) edited by CRISPR/Cas9 system to harbor mutation-corrected RUNX2 exhibited increased proximal promoter expression of RUNX2, while CCD iPSCs did not. We identified 2271 ncRNA genes with altered expression levels before and after differentiation, 31 of which showed at least 20-fold higher expression in Rev1 iPSCs. Bioinformatic analysis also categorized AC007392.3, LINC00379, RP11-122D10.1, and RP11-90J7.2 as enhancer regulatory regions, and HOXA-AS2, MIR219-2, and RP11-834C11.3 as dyadic regulatory regions of these ncRNAs. In addition, two miRNAs, termed MIR199A2 and MIR152, were found to have high enrichment of osteogenic-related terms. Upon further examination of the role of MIR152 on osteoblast differentiation, we found that MIR152 knockdown induced upregulation of ALP and COL1A1 in Saos-2 cells. Thus, ncRNAs were found to regulate the osteogenic differentiation potentials of hiPSCs that are used for bone regeneration and repair owing to their differentiation potentials. These data allow understanding ncRNA profiles of hiPSCs during osteogenesis.

Three-dimensional Coordinate System for Hemifacial Microsomia.

BACKGROUND: Hemifacial microsomia (HFM) is a congenital disorder characterized by facial asymmetry, but no midline reference has been established for evaluating facial morphology in patients with HFM. The purpose of this study was to develop a 3-dimensional coordinate system unaffected by the deformity of the external acoustic aperture or orbital circumference and to quantitatively evaluate craniofacial morphology in such patients. METHODS: We quantitatively evaluated craniofacial morphology using 3-dimensional measurements with the skull base as a reference. Using computed tomography data from 15 patients with HFM and 15 controls, a coordinate system was created for each patient, and left-right differences between measurement points were compared. RESULTS: When mandibular deformity was severe, the deformity of the posterior part of the palatine bone and lateral part of the orbit increased, but this trend was not evident for other measurement points. Thus, craniofacial deformity in HFM was not always related to mandibular deformity. Moreover, no difference was evident in the position of the hypoglossal canal between controls and patients with HFM. CONCLUSIONS: Quantitative assessments are possible using the coordinate system devised in this study, irrespective of the severity of HFM. The degree of mandibular deformity detailed in the Pruzansky classification was associated with the superoinferior deformity of the posterior part of the palatine bone and anteroposterior deformity of the lateral part of the orbit.

Surgical Orthodontic Treatment Involving Mandibular Premolar Extraction in Patient with Mandibular Retrusion Associated with Temporomandibular Joint Osteoarthritis.

Here, we report retention following surgical orthodontic treatment in a patient with vertical maxillary excess associated with temporomandibular joint osteoarthritis (TMJOA) and marked mandibular retrusion. The patient was a man aged 20 years 10 months who presented with the chief complaint of maxillary protrusion. The facial profile was of the convex type due to marked mandibular retrusion. In addition, the patient had a gummy smile. Intraoral findings revealed a Class II molar relation, +11 mm overjet, and 0 mm overbite. Mandibular dentition arch length discrepancy showed crowding of -2 mm, and the maxillary dentition showed a spaced arch of +5 mm. Panoramic radiographs confirmed flattening of the condylar head and proliferation of the bone margin. Cephalometric analysis of the skeletal pattern revealed that, horizontally, the maxilla was anterior and the mandible posterior; vertically, a dolichofacial pattern was noted. The anterior maxillary tooth axis was standard, but the anterior mandibular tooth axis showed labial inclination. Based on these findings, skeletal maxillary protrusion associated with TMJOA was diagnosed. Surgical orthodontic treatment comprised bilateral mandibular first premolar extraction with two-jaw surgery and genioplasty. Orthodontic treatment was performed with a multibracket system using a 0.22-slot pre-adjusted edgewise appliance. At 2 years and 11 months after initiation of treatment, the maxilla was transposed 6 mm upwards by orthognathic surgery and the mandible 17 mm anteriorly and 5 mm upwards by counterclockwise rotation. At 3 years and 10 months, the Pogonion was moved 6 mm anteriorly by genioplasty. At 4 years, orthodontic treatment was concluded on confirming satisfactory occlusion and improvement in facial features. At 2 years after completion of treatment, occlusion and the maxillofacial morphology remain stable, with almost no relapse. In addition, no temporomandibular joint disorder symptoms have occurred. Careful comprehensive follow-up observation will be continued.

Condition-specific Quality of Life Assessment at Each Stage of Class III Surgical Orthodontic Treatment -A Prospective Study.

Surgical orthodontic treatment has been reported to improve oral health-related quality of life (OHRQL). Such treatment comprises three stages: pre-surgical orthodontic treatment; orthognathic surgery; and post-surgical orthodontic treatment. Most studies have focused on change in OHRQL between before and after surgery. However, it is also necessary to evaluate OHRQL at the pre-surgical orthodontic treatment stage, as it may be negatively affected by dental decompensation compared with at pre-treatment. The purpose of this prospective study was to investigate the influence of surgical orthodontic treatment on QOL by assessing change in condition-specific QOL at each stage of treatment in skeletal class III cases. Twenty skeletal class III patients requiring surgical orthodontic treatment were enrolled in the study. Each patient completed the Orthognathic Quality of Life Questionnaire (OQLQ), which was developed for patients with dentofacial deformity. Its items are grouped into 4 domains: "social aspects of dentofacial deformity"; "facial esthetics"; "oral function"; and "awareness of dentofacial esthetics". The questionnaire was completed at the pre-treatment, pre-surgical orthodontic treatment, and post-surgical orthodontic treatment stages. The results revealed a significant worsening in scores between at pre-treatment and pre-surgical orthodontic treatment in the domains of facial esthetics and oral function (p<0.01), and between at pre-surgical orthodontic and post-surgical orthodontic treatment in all domains except awareness of dentofacial esthetics (p<0.05, p<0.01). A significant correlation was observed between a negative change in overjet and worsening OQLQ scores at the pre-surgical orthodontic treatment stage. Significant correlations were also observed between improvement in upper and lower lip difference, soft tissue pogonion protrusion, and ANB angle and improvement in OQLQ scores at the post-surgical orthodontic treatment stage. These results indicate that morphologic change influences OHRQL in patients undergoing surgical orthodontic treatment not only after surgery, but also during pre-surgical orthodontic treatment.

Dental Implant Treatment with Computer-assisted Surgery for Bilateral Agenesis of Maxillary Lateral Incisors: A Case Report.

Here, we report a case of dental implant treatment involving computer-assisted surgery for bilateral agenesis of the maxillary lateral incisors. The patient was a 39-year-old woman with the chief complaint of functional and esthetic disturbance due to maxillary and mandibular malocclusion. The treatment plan comprised non-extraction comprehensive orthodontic treatment and prosthodontic treatment for space due to the absence of bilateral maxillary lateral incisors. A preliminary examination revealed that the mesiodistal spaces left by the absent bilateral maxillary lateral incisors were too narrow for implant placement (right, 5.49 mm; left, 5.51 mm). Additional orthodontic treatment increased these spaces to approximately 6 mm, the minimum required for implant placement if risk of damage to the adjacent teeth due to inaccuracies in directionality of drilling is to be avoided. For dental implant treatment with computer-assisted surgery, preoperative planning/simulation was performed using Simplant® ver.12 software and a toothsupported surgical template fabricated using stereolithography. Two narrow-diameter implants were placed in a two-stage procedure. It was confirmed that there was sufficient distance between the implant fixtures and the roots of the adjacent teeth, together with no exposure of alveolar bone. Following a 4-month non-loading period, second-stage surgery and provisional restoration with a temporary screw-retained implant crown were performed. Cement-retained superstructures made of customized zirconia abutment and a zirconia-bonded ceramic crown were fitted as the final restoration. At 5 years after implant surgery, there were no complications, including inflammation of the peri-implant soft tissue and resorption of peri-implant bone. Computer-assisted implant surgery is useful in avoiding complications in bilateral agenesis of the maxillary lateral incisors when only a narrow mesiodistal space is available for implant placement.

Multidisciplinary treatment of peripheral osteoma arising from mandibular condyle in patient presenting with facial asymmetry.

While osteomas often occur in the orofacial area, it is relatively rare for one to occur in the temporomandibular joint area. Here, we report a patient who underwent multidisciplinary treatment including high condylectomy for peripheral osteoma arising in the left mandibular condyle. The patient was a 46-year-old woman with the chief complaint of facial asymmetry. Cephalometric analysis revealed skeletal anterior crossbite due to anterior deviation of the mandible, with chin deviation of 10 mm to the right. A computed tomography scan revealed bone hyperplasia in the mesiodistal and inner areas of the left mandibular condyle, which exhibited outward anterior displacement. Bone scintigraphy showed a circular area of strong radioisotope accumulation with indistinct boundaries, consistent with the lesion in the left mandibular condyle. The above findings led to a diagnosis of skeletal mandibular prognathism with facial asymmetry due to peripheral osteoma originating in the left mandibular condyle. After orthodontic treatment and surgical resection of the tumor and mandibular condyle, preservation and prosthetic treatment were undertaken. A well-balanced facial appearance and good occlusion were achieved.

Clinical study of temporary anchorage devices for orthodontic treatment--stability of micro/mini-screws and mini-plates: experience with 455 cases.

The aim of this retrospective study was to determine factors that might cause complications in use of temporary anchorage devices (TADs) for orthodontic anchorage. We investigated 904 TADs in 455 patients. Clinical diagnoses requiring orthodontic treatment were malocclusion, jaw deformity, various syndromes, cleft lip and palate and impacted teeth. All patients underwent surgery at Tokyo Dental College Chiba Hospital between November 2000 and June 2009. Three kinds of titanium screw of different diameter and length were used: self-drilling mini-screws (Dual Top Autoscrew® and OSAS®), pre-drilling micro-screws (K1 system®) and palatal screws (PIAS®). Mini-plates fixed with 2 or 3 screws (SAS system®) were also used for skeletal anchorage. Patients were aged between 8 and 68 years (25.7±9.8 years). A total of 460 screw-type and 444 plate-type TADs were used. These comprised the following: mini-plates, 444; self-drilling mini-screws, 225; pre-drilling micro-screws, 83; and palatal screws, 152. Each type of implant had a high success rate of over about 90%. Failure rates were as follows: micro-screws, 7%; mini-screws, 6%; palatal implants, 11%; and mini-plates, 6%. Inflammation rate occurring in soft tissue surrounding TADs was follows: plate-type, 7.6%; mini-screws, 1.3%; micro-screws, 0%; and palatal implants, 2.5%. Inflammation frequencies depended on degree of mucosal penetration. Granulation rate in soft tissue surrounding TADs occurred as follows: micro-screws, 5.7%; self-drilling mini-screws, 0%; palatal screws, 0.6%; plate-type, 0.9%. Both plate- and screwtype orthodontic implants showed excellent clinical performance.

Tooth axis and skeletal structures in mandibular molar vertical sections in jaw deformity with facial asymmetry using MPR images.

The objective of the present study was to investigate frontal morphological asymmetry in the mandibular molar region in terms of tooth axis and skeletal structures using vertical MPR sections in jaw deformity accompanied by facial asymmetry. Subjects consisted of 15 patients with jaw deformity accompanied by facial asymmetry aged 17.4 years to 37.8 years. There were four men and eleven women. Based on X-ray computed tomography (CT) scans, DICOM viewer software was used to prepare multiplanar reconstruction (MPR) sections. The mandible was then positioned on a reference plane based on the menton and left and right gonions, and a vertical MPR section passing through the mesial root of the first mandibular molar was prepared. The following measurements were made on both the shifted and non-shifted sides: maximum buccolingual width of the mandibular body; height of the mandibular body; inclination angle of the mandibular body; degree of buccal protrusion of the mandibular body; and inclination angle of the buccolingual tooth axis of the first molar. Furthermore, degree of median deviation in the menton was measured using frontal cephalograms. Differences in morphological parameters between the shifted and non-shifted sides were assessed. Furthermore, the relationship between median deviation and asymmetry were statistically analyzed. There was no significant asymmetry in the maximum buccolingual width of the mandibular body, the height of the mandibular body or the degree of buccal protrusion of the mandibular body. However, when compared to the shifted side, the inclination angle of the buccolingual tooth axis of the first molar for the non-shifted side was significantly greater. There was a relatively strong correlation between median deviation and inclination angle of the mandibular body. The above findings clarified that, in orthognathic surgery for jaw deformity accompanied by facial asymmetry, actively improving asymmetry in the buccolingual inclination of the tooth axis of the molar region during presurgical orthodontic treatment is important in achieving favorable post-treatment occlusal stability and facial symmetry.

Morphological evaluations in skeletal Class III malocclusion requiring maxillofacial surgery using orthognathic surgical analysis.

The purpose of this study was to establish a Japanese standard norm for orthognathic surgical analysis to be used in clinical applications and to clarify maxillofacial morphological characteristics in skeletal Class III malocclusions requiring orthognathic surgery. The materials were pretreatment lateral cephalometric radiographs in the relaxed lip posture from 50 subjects with skeletal Class III malocclusions diagnosed as requiring orthognathic surgery. The control group consisted of 50 subjects with normal occlusion and well-balanced faces. Detailed cephalometric measurements were recorded and analyzed statistically. The skeletal, dental, and soft tissue measurements from the normal group did not reveal any marked differences between the sexes. The Class III group exhibited a more retrognathic maxilla and prognathic mandible, a steeper mandibular plane, a more prominent chin, and a larger lower facial height in the skeletal measurements; a significant lingual inclination of the mandibular incisor in the dental measurement; and a more concave profile with prognathic mandible, a larger lower facial height, a more acute nasolabial angle and chin in the soft tissue measurements. We suggest that this analysis can be clinically useful in diagnosis, treatment planning, and posttreatment evaluation for orthognathic surgical cases who are Class III patients.