Focal osteoporotic bone marrow defect is an asymptomatic condition characterized by localized areas of decreased trabecular bone density within the jaw and is often detected incidentally on radiographic examination. Although it generally does not require treatment, it may increase the risk of complications during dental implant placement due to insufficient primary stability in areas of low bone density. This report describes three clinical cases of implant fixture displacement into focal osteoporotic bone marrow defects in the posterior mandible. Radiographic examinations revealed ill-defined radiolucent lesions without cortical expansion at the implant sites. One patient experienced inferior alveolar nerve injury following displacement, whereas no postoperative complications were observed in the remaining cases. These findings indicate that focal osteoporotic bone marrow defects may represent an underrecognized risk factor for implant displacement, and highlight the importance of careful preoperative radiographic assessment and cautious surgical planning in areas of suspected low bone density.

The aim of this study is to develop innovative multifunctional bone substitutes by engineering graphene oxide (GO) and doxorubicin (DOX)-conjugated whitlockite (WH) composites (WG@DOX) for enhanced bone regeneration and targeted drug delivery. To assess the physicochemical properties of WG@DOX composites, we performed a series of characterization techniques, including morphological analysis, X-ray diffraction, Fourier-transform infrared spectroscopy, photothermal measurements, drug release studies, and in vitro bioactivity evaluation. Leveraging GO's photothermal properties, WG@DOX exhibited enhanced heat generation under NIR laser irradiation. The bone particles demonstrated sustained, pH-sensitive, and light-triggered drug release. This led to superior biocompatibility and drug delivery, enabling potent synergistic chemo-photothermal therapy. Importantly, the WG@DOX composites exhibited a synergistic therapeutic effect, combining the cytotoxic effects of DOX chemotherapy with the localized hyperthermia induced by GO under NIR laser irradiation, leading to significant eradication of MG63 osteosarcoma cells. Furthermore, the synergistic effects of GO and Mg2+ ions within the WH-GO composite particles markedly enhanced osteoblast adhesion, proliferation, and osteogenic differentiation by upregulating key osteogenic proteins.

Oral squamous cell carcinoma (OSCC) is highly heterogeneous and metastatic, and the mechanisms driving OSCC development, progression, and metastasis remain elusive. Here, we performed single-cell RNA sequencing on 231,442 cells obtained from the tumor core (TC), tumor periphery (TP), adjacent surrounding tissue (ST), and metastatic lymph node (mLN) samples of 10 patients with human papillomavirus (HPV)-negative OSCC. TP and TC showed no major immune cell phenotype differences. Interestingly, partial EMT (p-EMT) cells showed significant activation of glycolysis and hypoxia signatures, serving as potential biomarkers for clinical outcomes. Moreover, p-EMT scores of epithelial cells positively correlated with M2 scores of tumor-associated macrophages, while the proportion of p-EMT at TP was negatively associated with that of GZMB + exhausted CD8+ T cells with cytotoxic potential and TNFRSF9 + mast cells, conferring an adverse prognosis. Our study provides insights into understanding the interplay between intratumoral heterogeneity and the tumor microenvironment of advanced HPV-negative OSCC.

Schizophyllan (SPG), a β-glucan from Schizophyllum commune, is recognized for its antioxidant, immunoregulatory, and anticancer activities. In this study, its effects on bone cells, particularly osteoclasts and osteoblasts, were examined. We demonstrated that SPG dose-dependently inhibited osteoclastogenesis and reduced gene expression associated with osteoclast differentiation. SPG also decreased bone resorption and F-actin ring formation. This inhibition could have been due to the downregulation of transcription factors c-Fos and nuclear factor of activated T cells 1 (NFATc1) via the MAPKs (JNK and p38), IκBα, and PGC1β/PPARγ pathways. In coculture, SPG lowered osteoclastogenic activity in calvaria-derived osteoblasts by reducing macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor–κB ligand (RANKL) expression. In addition, SPG slightly enhanced osteoblast differentiation, as evidenced by increased differentiation marker gene expression and alizarin red staining. It also exhibited antiresorptive effects in a lipopolysaccharide-induced calvarial bone loss model. These results indicated a dual role of SPG in bone cell regulation by suppressing osteoclastogenesis and promoting osteoblast differentiation. Thus, SPG could be a therapeutic agent for bone resorption-related diseases such as osteoporosis, rheumatoid arthritis, and periodontitis.

Previous reports on complex odontomas in the maxillary sinus describe cases that are associated with the alveolar process and extend into the maxillary sinus. This report presents a rare case of giant complex odontoma in the maxillary sinus, arising entirely within the maxillary sinus and unassociated with the alveolar process. In this case, the lesion was surgically removed through Caldwell-Luc operation. under general anesthesia, and the bony window was closed with titanium mesh.

Pathological fracture is one of the most serious complications in medication-related osteonecrosis of the jaw (MRONJ). This case is a report of an 87-year-old woman who had been diagnosed with pathological fracture due to MRONJ. The authors performed minimally invasive and conservative treatment, such as intraoral dressing, antibiotic therapy, and simple debridement, for patients with pathologic fractures due to MRONJ. After 1 year, the inflammatory symptoms disappeared and pathological fractures spontaneously recovered.

Background: Mesenchymal stem cells (MSCs) are pluripotent stromal cells that are among the most appealing candidates for regenerative medicine and may aid in the repair and regeneration of skeletal disorders through multiple mechanisms, including angiogenesis, differentiation, and response to inflammatory conditions. Tauroursodeoxycholic acid (TUDCA) has recently been used in various cell types as one of these drugs. The mechanism of osteogenic differentiation by TUDCA in hMSCs remains unknown. Methods: Cell proliferation was performed by the WST-1 method, and alkaline phosphatase activity and alizarin red-sulfate staining were used to confirm the osteogenic differentiation indicator. Expression of genes related to bone differentiation and specific genes related to signaling pathways was confirmed by quantitative real-time polymerase chain reaction. Results: We found that cell proliferation was higher as the concentration increased, and showed that the induction of osteogenic differentiation was significantly enhanced. We also show that osteogenic differentiation genes were upregulated, with the expression of the epidermal growth factor receptor (EGFR) and cAMP responsive element binding protein 1 (CREB1) being specifically high. To confirm the participation of the EGFR signaling pathway, the osteogenic differentiation index and expression of osteogenic differentiation genes were determined after using an EGFR inhibitor. As a result, EGFR expression was remarkably low, and that of CREB1, cyclin D1, and cyclin E1 was also significantly low. Conclusions: Therefore, we suggest that TUDCA-induced osteogenic differentiation of human MSCs is enhanced through the EGFR/p-Akt/CREB1 pathway.

Background: As stem cells are considered a promising cell source for tissue engineering, many culture strategies have been extensively studied to generate in vitro stem cell-based tissue constructs. However, most approaches using conventional tissue culture plates are limited by the lack of biological relevance in stem cell microenvironments required for neotissue formation. In this study, a novel perfusion rotating wall vessel (RWV) bioreactor was developed for mass-production of stem cell-based 3D tissue constructs. Methods: An automated RWV bioreactor was fabricated, which is capable of controlling continuous medium perfusion, highly efficient gas exchange with surrounding air, as well as low-intensity pulsed ultrasound (LIPUS) stimulation. Embryonic stem cells encapsulated in alginate/gelatin hydrogel were cultured in the osteogenic medium by using our bioreactor system. Cellular viability, growth kinetics, and osteogenesis/mineralization were thoroughly evaluated, and culture media were profiled at real time. The in vivo efficacy was examined by a rabbit cranial defect model. Results: Our bioreactor successfully maintained the optimal culture environments for stem cell proliferation, osteogenic differentiation, and mineralized tissue formation during the culture period. The mineralized tissue constructs produced by our bioreactor demonstrated higher void filling efficacy in the large bone defects compared to the group implanted with hydrogel beads only. In addition, the LIPUS modules mounted on our bioreactor successfully reached higher mineralization of the tissue constructs compared to the groups without LIPUS stimulation. Conclusion: This study suggests an effective biomanufacturing strategy for mass-production of implantable mineralized tissue constructs from stem cells that could be applicable to future clinical practice.

Tissue adhesives are widely used in various medical fields for tissue bonding and wound closure. Existing glue-type tissue adhesives have disadvantages such as low biocompatibility or a long reaction time to achieve firm tissue adhesion. Herein we developed photocurable tissue adhesives by introducing photocrosslinkable methacrylate (MA) groups into biodegradable hyaluronic acid (HA) that enables strong tissue adhesion and wound sealing. The photocurable tissue adhesive formed a stable hydrogel layer with good tissue adhesion following short UV exposure (<5 s). By controlling the substitution rate of MA and polymer concentration, the mechanical properties and adhesion strength of the tissue adhesive could be easily manipulated. From the incisional wound animal model, the HA-based tissue adhesive used in this study showed better tissue adhesion and faster wound healing efficacy compared to commercial glues. Considering the high biocompatibility and biodegradability of HA, this photocurable adhesive would be useful in wound healing of various soft tissues.

Mandibular prognathism causes functional and esthetic problems. Therefore, many studies have been conducted to understand its etiology. Following our previous study, which revealed that the major characteristic of the mandible with prognathism is the volume/length ratio of the mandibular body and condyle, we analyzed the volume and orientation of the masseter muscle, which inserts into the mandibular body, expecting that the difference in the size of the masseter muscle causes the difference in the mandibular size. This study compared the masseter muscle of the participants in the prognathic group to those in the normal group on the volume/length ratio and orientation. The masseter muscle ratios (volume/length); the angle between the superficial and deep head of the masseter muscle; and the three planes (the palatal, occlusal, and mandibular) were analyzed. A total of 30 participants constituted the normal group (male: 15, female: 15) and 30 patients, the prognathic group (male: 15, female: 15). The results showed that the volume/length ratio of the masseter of the normal group was greater than that of the prognathic group (p < 0.05). In addition, the orientation of both the superficial and deep head of the masseter of the participants in the normal group was more vertical with respect to the mandibular plane than that of the prognathic group (p < 0.05). We concluded that the mechanical disadvantage of the masseter muscle of the prognathic group is attributed to mandibular prognathism.

Paired box protein 5 (Pax5) is a crucial transcription factor responsible for B-cell lineage specification and commitment. In this study, we identified a negative role of Pax5 in osteoclastogenesis. The expression of Pax5 was time-dependently downregulated by receptor activator of nuclear factor kappa B (RANK) ligand (RANKL) stimulation in osteoclastogenesis. Osteoclast (OC) differentiation and bone resorption were inhibited (68.9% and 48% reductions, respectively) by forced expression of Pax5 in OC lineage cells. Pax5 led to the induction of antiosteoclastogenic factors through downregulation of B lymphocyte-induced maturation protein 1 (Blimp1). To examine the negative role of Pax5 in vivo, we generated Pax5 transgenic (Pax5Tg) mice expressing the human Pax5 transgene under the control of the tartrate-resistant acid phosphatase (TRAP) promoter, which is expressed mainly in OC lineage cells. OC differentiation and bone resorption were inhibited (54.2–76.9% and 24.0–26.2% reductions, respectively) in Pax5Tg mice, thereby contributing to the osteopetrotic-like bone phenotype characterized by increased bone mineral density (13.0–13.6% higher), trabecular bone volume fraction (32.5–38.1% higher), trabecular thickness (8.4–9.0% higher), and trabecular number (25.5–26.7% higher) and decreased trabecular spacing (9.3–10.4% lower) compared to wild-type control mice. Furthermore, the number of OCs was decreased (48.8–65.3% reduction) in Pax5Tg mice. These findings indicate that Pax5 plays a negative role in OC lineage specification and commitment through Blimp1 downregulation. Thus, our data suggest that the Pax5–Blimp1 axis is crucial for the regulation of RANKL-induced osteoclastogenesis.

This paper proposes a convolutional neural network (CNN)-based deep learning model for predicting the difficulty of extracting a mandibular third molar using a panoramic radiographic image. The applied dataset includes a total of 1053 mandibular third molars from 600 preoperative panoramic radiographic images. The extraction difficulty was evaluated based on the consensus of three human observers using the Pederson difficulty score (PDS). The classification model used a ResNet-34 pretrained on the ImageNet dataset. The correlation between the PDS values determined by the proposed model and those measured by the experts was calculated. The prediction accuracies for C1 (depth), C2 (ramal relationship), and C3 (angulation) were 78.91%, 82.03%, and 90.23%, respectively. The results confirm that the proposed CNN-based deep learning model could be used to predict the difficulty of extracting a mandibular third molar using a panoramic radiographic image.

Facial photographs of the subjects are often used in the diagnosis process of orthognathic surgery. The aim of this study was to determine whether convolutional neural networks (CNNs) can judge soft tissue profiles requiring orthognathic surgery using facial photographs alone. 822 subjects with dentofacial dysmorphosis and / or malocclusion were included. Facial photographs of front and right side were taken from all patients. Subjects who did not need orthognathic surgery were classified as Group I (411 subjects). Group II (411 subjects) was set up for cases requiring surgery. CNNs of VGG19 was used for machine learning. 366 of the total 410 data were correctly classified, yielding 89.3% accuracy. The values of accuracy, precision, recall, and F1 scores were 0.893, 0.912, 0.867, and 0.889, respectively. As a result of this study, it was found that CNNs can judge soft tissue profiles requiring orthognathic surgery relatively accurately with the photographs alone.

Odontogenic myxoma is a benign tumor, mostly located in the mandible. It shows locally aggressive behavior and requires surgical removal. Common treatment options for reconstructing the bone defects are immediate or delayed autologous bone graft or free flap. In this article, the authors present the successful reconstruction with autogenous bone graft and autologous human bone marrow mesenchymal stem, followed by distraction osteogenesis, dental implant placement and prosthodontic restoration in the mandibular defect.

Angiogenesis is a crucial process during bone tissue regeneration. The aim of this study was to investigate the angiogenic activity and the potentiation of bone regeneration via angiogenesis using tauroursodeoxycholic acid (TUDCA) in vitro and in vivo. We investigated the effect of TUDCA on proliferation and angiogenic differentiation in human umbilical vein endothelial cells (HUVECs) and the associated signaling pathway. Proliferation was determined using crystal violet assay. Angiogenic effects were evaluated based on cell migration and tube formation. In order to explore TUDCA-signaling pathways, phosphorylation of mitogen activated protein kinase, protein kinase B (AKT), and endothelial nitric oxide synthase (eNOS) was determined using western blot. Furthermore, in vivo bone formation and angiogenesis were determined using a New Zealand outbred albino rabbit calvarial defect model, while angiogenesis and bone formation were evaluated using micro-CT and histological analysis. Our results show that TUDCA significantly increased cell proliferation. Moreover, TUDCA enhanced cell migration and tube formation in HUVECs. TUDCA increased the phosphorylation of AKT, ERK1/2, c-Jun N-terminal kinase, and eNOS. Specific inhibitors of ERK1/2 (PD98059), JNK (SP600125), and AKT (AKT1/2) inhibited the TUDCA-induced migration and tube formation, while the p38 inhibitor (SB203580) did not. The in vivo study used TUDCA to accelerate new blood vessel formation and promoted bone formation in rabbit calvarial defect model. These results indicate that TUDCA plays a critical role in enhancing the angiogenesis of endothelial cells and in vivo new bone regeneration. The use of TUDCA may contribute to the regeneration of bone tissue by improving angiogenesis.

The purpose of this study was to evaluate the skeletal units of a normal mandible (class I) and a prognathic mandible (class III), to compare the groups, and to investigate the key functional unit responsible for mandibular prognathism. Hemi-mandibles of 101 cases were evaluated by cone-beam computed tomography. Of these, 50 cases had Class I and 51 had Class III mandibles. The length, volume, and volume/length ratio of each skeletal unit were measured. The ratios of the condyle, body unit, and sum of the hemi-mandible between Class I and Class III showed statistically significant results (P<0.05). However, the ratios of angle, coronoid, and symphysis units did not show any statistical significance on comparison. Dependent on gender, in males the ratio of the condyle of the hemi-mandible showed statistically significant results (P<0.05). Meanwhile in females the ratio of the body and sum of the hemi-mandible showed statistically significant results (P<0.05). Accordingly, the mandibular body and condylar units are thinner in mandibular prognathism. On the basis of the functional matrix theory to determine the aetiology of mandibular prognathism, the key skeletal units are the body and condylar units.

consistent and reproducible results.Factors such as endogenous peroxidase blocking, antibody concentration and incubation time, chromogen system and counterstains are important parameters that should be optimized for individual studies.

Cemento-osseous dysplasia is a well-known condition in which healthy bone becomes sclerotic. Hypovascularity of the lesion (caused by cementum-like deposits) increases the risk of secondary infection and osteomyelitis, which can also be induced by the placement of implants.