Lymphatic vessels in bone support regeneration after injury.

Blood and lymphatic vessels form a versatile transport network and provide inductive signals to regulate tissue-specific functions. Blood vessels in bone regulate osteogenesis and hematopoiesis, but current dogma suggests that bone lacks lymphatic vessels. Here, by combining high-resolution light-sheet imaging and cell-specific mouse genetics, we demonstrate presence of lymphatic vessels in mouse and human bones. We find that lymphatic vessels in bone expand during genotoxic stress. VEGF-C/VEGFR-3 signaling and genotoxic stress-induced IL6 drive lymphangiogenesis in bones. During lymphangiogenesis, secretion of CXCL12 from proliferating lymphatic endothelial cells is critical for hematopoietic and bone regeneration. Moreover, lymphangiocrine CXCL12 triggers expansion of mature Myh11+ CXCR4+ pericytes, which differentiate into bone cells and contribute to bone and hematopoietic regeneration. In aged animals, such expansion of lymphatic vessels and Myh11-positive cells in response to genotoxic stress is impaired. These data suggest lymphangiogenesis as a therapeutic avenue to stimulate hematopoietic and bone regeneration.

The Effect of Oral Mucosal Disinfection with Povidone-Iodine in Oral and Maxillofacial Surgery.

This study enrolled 60 patients aged 28 to 76 years who were oral malignancy undergoing radical surgery for more than 3 hours to assess the disinfection effect of povidone-iodine in oral and maxillofacial surgery which is a clean-contaminated wound. The authors collected and compared the sample from oral mucosa and counted the colony-forming units before disinfection, after disinfection for 10 minutes, 1, 2, 3, and 4 hours. The results showed that the oral bacterial colony-forming units significantly decreased after disinfecting with povidone-iodine and the effect existed for 2 hours and the colony-forming units of 3 hours after disinfection showed statistically significant increase. In oral and maxillofacial surgery, povidone-iodine can effectively disinfect the mouth and maintain a certain period of time. Therefore, to reduce the number of oral mucosa microorganisms, it is recommended to disinfect the oral cavity again after 3 hours.

FERMT2 upregulation in CAFs enhances EMT of OSCC and M2 macrophage polarization.

OBJECTIVES: FERMT2 upregulation was associated with malignant tumor behaviors, including epithelial-to-mesenchymal (EMT). This study aimed to characterize the expression profile of FERMT2 in oral squamous cell carcinoma (OSCC) and to explore its involvement in the tumor microenvironment sculptured by oral cancer-associated fibroblasts (OCAFs). MATERIALS: Previous bulk-seq (TCGA-HNSC) and single-cell RNA-seq data sets were retrieved for bioinformatic analysis. Human OSCC lines SCC15 and CAL27, primary normal oral fibroblasts (NOFs), OCAFs, and THP-1 cells were used for intro studies. RESULTS: FERMT2 expression was significantly higher in CAFs compared with OSCC tumor cells and normal fibroblasts. Higher FERMT2 expression might independently predict unfavorable disease-specific survival (DSS) in patients with OSCC. Knockdown of FERMT2 suppressed the expression and secretion of IGFBP7, SPARC, TIMP3, COL4A1, and IGFBP4 in OCAFs. OCAFs with FERMT2 knockdown had significantly weakened capability to induce the invasion of OSCC cells and the expression of mesenchymal markers. FERMT2 knockdown impaired the inducing effect of OCAFs on the migration of M0 macrophages and the expression of M2 macrophage markers. CONCLUSIONS: FERMT2 could modulate the production and secretion of IGFBP7, SPARC, COL4A1, and IGFBP4 in OCAFs, thereby inducing the EMT of OSCC and M2 macrophage polarization.

Reconstruction of Buccal-penetrating Defects Using the Double-folded Lateral Arm Free Flap.

The reconstruction of buccal-penetrating defects remains challenging. The present study aims to explore the application value of the lateral arm free flap (LAFF) on the reconstruction of buccal-penetrating defects with the hope of providing a better option for clinical practice. Nineteen patients with this kind of issue posed by either tumor resections or deformities in the craniofacial regions were recruited in this study, and LAFF was employed to reconstruct these defects by double folding and individually designing the flap. All the flaps prepared for these subjects in our study survived, and the postoperative assessment of these subjects receiving LAFF revealed that this approach to managing buccal-penetrating defects is able to achieve satisfactory results in terms of appearance and functional recovery. Therefore, our study suggests that LAFF is 1 of the promising flaps to reconstruct the buccal-penetrating defects.

Synchronous Reconstruction of the Jaw Using a "One and a Half"-Barrel Fibular Bone Graft for Ossifying Fibroma Patients.

BACKGROUND: Ossifying fibroma is one of the common benign tumors that affect the appearance and functions of the jaw. Ossifying fibroma may exhibit a wide range of biological behaviors, leading to deformities involving the jaw and other secondary facial deformities. Hence, to improve the function of the jaw and the patient's general facial appearance (bearing in mind each patient's facial shape and, or appearance), the authors thus, however, used a ''one and a half"-barrel fibular bone graft to achieve the ideal height and radian of the bone graft. CASE PRESENTATION: Between July 2017 and January 2021, the authors retrospectively collected and analyzed clinical and surgical data from 39 patients who had undergone operations in our hospital. Twenty patients were operated on using our new surgical method, whereas 19 patients received conventional or debulking operation. Clinical factors associated with the operation were assessed, including classification of the jaw defects, perioperative complications, and postoperative outcomes. RESULTS: All the flaps ultimately survived. According to the postoperative satisfaction survey, patients who underwent reconstruction were satisfied with their postoperative facial appearance, with an average of 8.5 out of 10. Based on the preoperative clinical data, 26 patients had suitable bone grafts for dentures to improve their oral function. CONCLUSIONS: A ''one and a half''-barrel fibular bone graft effectively improves the facial appearance of patients and as well as provides an appropriate height and radian for the bone graft.

Elective Neck Dissection Versus Observation in Squamous Cell Carcinoma of Oral Cavity With Clinically N0 Neck: A Systematic Review and Meta-Analysis of Prospective Studies.

PURPOSE: To assess the possible benefits of elective neck dissection (END) in patients with squamous cell carcinoma (SCC) of the oral cavity and clinically N0 neck. MATERIALS AND METHODS: Medline, Embase, the China National Knowledge Infrastructure, and the Wan Fang Database were systematically searched. A meta-analysis was performed to evaluate the possible benefits of END to such patients. RESULTS: Six prospective studies involving 865 patients fulfilled the inclusion criteria. Meta-analysis of all included studies showed that END substantially lowered the risk of regional recurrences (risk ratio [RR] = 0.27; 95% confidence interval [CI], 0.21-0.36) in the fixed-effect model compared with observation only. Three of the 6 included studies showed that the specific death rate related to regional recurrences was lower in the END group than in the observation group in the fixed-effect model (RR = 0.35; 95% CI, 0.19-0.65). The mean metastasis rate of occult cervical lymph node was 30.27% (standard deviation, 9.42%). When the fixed-effect model was applied, 4 of the 6 included studies showed less recurrence in the END group compared with the observation group (RR = 0.53; 95% CI, 0.44-0.64). CONCLUSIONS: END substantially decreases recurrences and deaths related to regional recurrences in early-stage SCC of the oral cavity with clinically N0 neck, especially SCC of the oral tongue and floor of the mouth, which is necessary for such patients.

Precision diagnosis and antidiastole on supernumerary cusp of tooth by CBCT.

PURPOSE: Based on a case of supernumerary cusp on the bucca of left maxillary second molar diagnosed by cone beam computed tomography (CBCT), its genesis, diagnosis and antidiastole are to be analysed. The clinic implication of CBCT is correspondingly discussed. METHODS: The supernumerary cusp was diagnosed by oral general examination, intra-oral radiograph and CBCT. The features of supernumerary cusp, fused tooth, geminated tooth and concrescence tooth, especially differentiate points among them were discussed. RESULTS: The case of supernumerary cusp on the bucca of left maxillary second molar was diagnosed definitely by the combined application of oral general examination, periapical radiograph and CBCT. CONCLUSION: Supernumerary cusp on the bucca of left maxillary second molar is a rare phenomenon, which is difficult to be differentiated from other tooth deformities. CBCT can improve accuracy of diagnosis.

Association between COVID 19 exposure and expression of malignant pathological features in oral squamous cell carcinoma: A retrospective cohort study.

OBJECTIVES: To analyze the relationship between the clinical and pathological characters of OSCC and COVID 19 exposure. MATERIALS AND METHODS: A retrospective cohort study in patients with OSCC with or without COVID 19 was performed. A total of 200 OSCC patients treated with surgery from 2019 to 2023 were included. Clinical and pathological features were analysed between two groups. Characters with statistical difference were further analysed by performing univariate analysis and logistic regression analysis. RESULTS: The expression of Ki67 (n = 57, 71.3 %, P < 0.001) and CyclinD1 (n = 64, 80 %, P < 0.001) in OSCC with the exposure history of COVID 19 is higher than that in patients never exposed to COVID 19. COVID 19 exposure history is an independent influencing factor for higher expression of Ki67 (OR = 4.04, 95 % CI: 1.87-8.72, P < 0.001) and CyclinD1 (OR = 5.45, 95 % CI: 2.56-11.60, P < 0.001). CONCLUSION: COVID 19 may suggest more invasive malignant biological behavior of cancer cells in OSCC.

Deciphering the spatial distribution of Gli1-lineage cells in dental, oral, and craniofacial regions.

The craniofacial bone, crucial for protecting brain tissue and supporting facial structure, undergoes continuous remodeling through mesenchymal (MSCs) or skeletal stem cells (SSCs) in their niches. Gli1 is an ideal marker for labeling MSCs and osteoprogenitors in this region, and Gli1-lineage cells are identified as pivotal for bone growth, development, repair, and regeneration. Despite its significance, the distribution of Gli1-lineage cells across the dental, oral, and craniofacial (DOC) regions remains to be systematically explored. Utilizing tissue-clearing and light sheet fluorescence microscopy (LSFM) with a Gli1CreER; tdTomatoAi14 mouse model, we mapped the spatial distribution of Gli1-lineage cells throughout the skull, focusing on calvarial bones, sutures, bone marrow, teeth, periodontium, jaw bones, and the temporomandibular joint (TMJ). We found Gli1-lineage cells widespread in these areas, underscoring their significance in DOC regions. Additionally, we observed their role in repairing calvarial bone defects, providing novel insights into craniofacial biology and stem cell niches and enhancing our understanding of stem cells and their progeny's behavior in vivo.

This study investigates the presence and role of a specific stem cell population, known as Gli1-lineage cells, in various parts of the skull and facial bones. Using advanced imaging techniques, we found that these cells are widely distributed across the dental, oral, and craniofacial regions, especially in the cranial sutures, teeth, and jaw. Notably, Gli1-lineage cells migrate to the injury site, which is essential in bone repair and regeneration. These findings enhance our understanding of how stem cells contribute to healing and development in the craniofacial region.

OSCC-derived EVs educate fibroblasts and remodel collagen landscape.

Cancer-associated myofibroblasts (mCAFs) represent a significant component of the tumor microenvironment due to their contributions to extracellular matrix (ECM) remodeling. The pro-tumor mechanisms of extracellular vesicles (EVs) by regulating mCAFs and related collagens remain poorly understood in oral squamous cell carcinoma (OSCC). In this study, through analysis of single-cell sequencing data and immunofluorescence staining, we confirmed the increased presence of mCAFs and enrichment of specific collagen types in OSCC tissues. Furthermore, we demonstrated that OSCC-derived EVs promote the transformation of fibroblasts into mCAFs, leading to tumor invasion. Proteomic analysis identified the presence of TGF-ß1 in EVs and revealed its role in inducing mCAFs via the TGF-ß1/Smad3 signaling pathway. Experiments in vivo confirmed that EVs, particularly those carrying TGF-ß1, trigger COL18high COL5high matrix deposition, thereby forming the pro-tumor ECM in OSCC. In summary, our investigation unveils the significant involvement of OSCC-derived EVs in orchestrating the differentiation of fibroblasts into mCAFs and modulating specific collagen types within the ECM. Therefore, this study provides a theoretical basis for targeting the EV-mediated TGF-ß1 signaling pathway as a potential therapeutic strategy for OSCC.

ORAI2 is Important for the Development of Early-Stage Postirradiation Fibrosis in Salivary Glands.

PURPOSE: Although postirradiation hyposalivation significantly impairs patient quality of life, the underlying mechanisms driving radiation-induced salivary gland fibrosis and hyposalivation remain poorly understood. This study aims to explore the role of calcium-mediated signaling pathways in radiation-induced salivary gland fibrosis. METHODS AND MATERIALS: Primary human submandibular gland (SG) cells and C57BL/6J female mouse SGs were exposed to irradiation to model fibrosis development. Following 15 Gy irradiation exposure, RNA sequencing and bioinformatic analysis were conducted on mouse SGs. The effects of store-operated calcium entry (SOCE) inhibition using SKF96365 and YM58483 on fibrosis markers were assessed in vitro and in vivo. Additionally, the involvement of ORAI2 protein and the newly identified JNK/NFAT1/transforming growth factor ß1 (TGF-ß1) signaling axis in SG fibrosis was explored. RESULTS: We identified that the calcium release-activated calcium modulator ORAI2 was important in promoting early-stage postirradiation fibrosis in SGs. Calcium channel signaling was activated in both human patients and irradiated C57BL/6J female mice SGs. Inhibition of SOCE signaling effectively blocked fibrosis in an ORAI2-dependent manner 30 days after irradiation. Our mechanistic studies revealed a novel ORAI2/JNK/NFAT1 axis within the SOCE pathway critical in driving TGF-ß1-mediated fibrogenesis. Encouragingly, pharmacologic inhibition of NFAT1 significantly mitigated radiation-induced SG fibrosis and restored saliva flow to 84.61% of normal levels in treated mice 30 days after irradiation, without detectable side effects. CONCLUSIONS: Our findings highlight the significance of the ORAI2-mediated calcium signaling pathway, specifically via the ORAI2/JNK/NFAT1 axis, in promoting TGF-ß1 expression and contributing to the development of early-stage salivary gland fibrosis following irradiation exposure. Targeting the ORAI2/JNK/NFAT1 axis emerges as a promising therapeutic strategy to alleviate radiation-induced hyposalivation and fibrosis, potentially improving the quality of life for patients undergoing radiation therapy.

Evaluation of a newly developed oral and maxillofacial surgical robotic platform (KD-SR-01) in head and neck surgery: a preclinical trial in porcine models.

Traditional open head and neck surgery often leaves permanent scars, significantly affecting appearance. The emergence of surgical robots has introduced a new era for minimally invasive surgery. However, the complex anatomy of the head and neck region, particularly the oral and maxillofacial areas, combined with the high costs associated with established systems such as the da Vinci, has limited the widespread adoption of surgical robots in this field. Recently, surgical robotic platform in China has developed rapidly, exemplified by the promise shown by the KangDuo Surgical Robot (KD-SR). Although the KD-SR has achieved some results comparable to the da Vinci surgical robot in urology and colorectal surgery, its performance in complex head and neck regions remains untested. This study evaluated the feasibility, effectiveness, and safety of the newly developed KD-SR-01, comparing it with standard endoscopic systems in head and neck procedures on porcine models. We performed parotidectomy, submandibular gland resection, and neck dissection, collected baseline characteristics, perioperative data, and specifically assessed cognitive workload using the NASA-TLX. None of the robotic procedures were converted to endoscopic or open surgery. The results showed no significant difference in operation time between the two groups (P = 0.126), better intraoperative bleeding control (P = 0.001), and a significant reduction in cognitive workload (P < 0.001) in the robotic group. In conclusion, the KD-SR-01 is feasible, effective, and safe for head and neck surgery. Further investigation through well-designed clinical trials with long-term follow-up is necessary to establish the full potential of this emerging robotic platform.

Case of primary extracranial meningioma of the maxillary sinus presenting as buccal swelling associated with headache: A case report.

BACKGROUND: Meningiomas are benign tumors that originate from the meningothelial arachnoid cells, but they rarely develop extracranially. There is no specific surgical guideline for resecting them in the maxillary sinus, and little is known about their biological behavior and operative management. CASE SUMMARY: We present a 54-year-old female patient referred to our department with a primary extracranial meningioma that presented as buccal swelling associated with headache. On clinical examination the mass was non-tender, fixed, sessile and non-pulsatile situating in the right maxillary sinus. Computed tomography scan showed a well-defined mass of 7 cm × 6 cm × 6 cm compressing the surrounding structures. Magnetic resonance imaging revealed a well circumscribed heterogenous lesion with necrotic center and relatively hypointense on T2-weighted imaging. Imaging studies revealed no evidence of intracranial extension and metastatic nests. Biopsy showed grade I primary extracranial with low mitotic activity. Total maxillectomy with excision of tumor and adjacent paranasal structures following reconstruction of the orbit and maxilla with tissue patch was done by the maxillofacial surgeon. The biopsy reported fibrous meningioma based on the hematoxylin and eosin section. On immunohistochemistry the tumor cells were positive for vimentin, focally positive for epithelial membrane antigen and CD99 and negative for signal transducer and activator of transcription 6. The mass was removed surgically with reconstruction, and the pathological studies confirmed the diagnosis to be an extracranial meningioma. The present study briefly reviews the current knowledge concerning the diagnosis and treatment of extracranial meningiomas in the head and neck area and offers suggestions for managing extracranial meningiomas in the paranasal sinuses. CONCLUSION: To conclude, extracranial meningiomas in the paranasal sinuses may be successfully managed by surgical treatment without evident post-surgery complications.

Diversity of Vascular Niches in Bones and Joints During Homeostasis, Ageing, and Diseases.

The bones and joints in the skeletal system are composed of diverse cell types, including vascular niches, bone cells, connective tissue cells and mineral deposits and regulate whole-body homeostasis. The capacity of maintaining strength and generation of blood lineages lies within the skeletal system. Bone harbours blood and immune cells and their progenitors, and vascular cells provide several immune cell type niches. Blood vessels in bone are phenotypically and functionally diverse, with distinct capillary subtypes exhibiting striking changes with age. The bone vasculature has a special impact on osteogenesis and haematopoiesis, and dysregulation of the vasculature is associated with diverse blood and bone diseases. Ageing is associated with perturbed haematopoiesis, loss of osteogenesis, increased adipogenesis and diminished immune response and immune cell production. Endothelial and perivascular cells impact immune cell production and play a crucial role during inflammation. Here, we discuss normal and maladapted vascular niches in bone during development, homeostasis, ageing and bone diseases such as rheumatoid arthritis and osteoarthritis. Further, we discuss the role of vascular niches during bone malignancy.

Sentinel lymph node biopsy versus elective neck dissection in squamous cell carcinoma of the oral cavity with a clinically N0 neck: Systematic review and meta-analysis of prospective studies.

Sentinel lymph node biopsy (SLNB) is an emerging strategy for managing early-stage oral squamous cell carcinoma (SCC) with a clinically N0 (cN0) neck. However, the role of SLNB in this scenario is debatable. Herein, relevant literature was systematically reviewed, and a meta-analysis was performed to evaluate the potential dividends of SLNB compared to elective neck dissection (END) for these patients. The meta-analysis, including six prospective studies, showed comparable results of the two management strategies in terms of regional recurrence (risk ratio [RR] = 0.99; 95% confidence interval [CI], 0.58-1.70), 5-year disease-free survival (RR = 0.99; 95% CI, 0.87-1.11), and 5-year overall survival (RR = 1.01; 95% CI, 0.90-1.13). Fewer adverse events occurred in the SLNB arm than in the END arm (RR = 0.12; 95% CI, 0.02-0.70). Overall, SLNB results in as favorable an oncologic prognosis for patients with cN0 oral SCC as END, while significantly lessening side effects and unnecessary surgeries.

Advances of adipose-derived mesenchymal stem cells-based biomaterial scaffolds for oral and maxillofacial tissue engineering.

The management of oral and maxillofacial tissue defects caused by tumors, trauma, and congenital or acquired deformities has been a major challenge for surgeons over the last few decades. Autologous tissue transplantation, the gold standard of tissue reconstruction, is a valid method for repairing the oral and maxillofacial functions and aesthetics. However, several limitations hinder its clinical applications including complications of donor sites, limited tissue volume, and uncertain long-term outcomes. Adipose-derived mesenchymal stem cells (ADMSCs) widely exist in adipose tissue and can be easily obtained through liposuction. Like the bone marrow-derived mesenchymal stem cells (BMSCs), ADMSCs also have the multi-pluripotent potencies to differentiate into osteoblasts, chondrocytes, neurons, and myocytes. Therefore, the multilineage capacity of ADMSCs makes them valuable for cell-based medical therapies. In recent years, researchers have developed many candidates of ADMSCs-based biomaterial scaffolds to cater for the needs of oral and maxillofacial tissue engineering due to their superior performance. This review presents the advances and applications of ADMSCs-based biomaterial scaffolds, and explores their tissue engineering prospects in oral and maxillofacial reconstructions.

Nanotechnology-based drug delivery systems for enhanced diagnosis and therapy of oral cancer.

Oral cancer is a common malignant life-threatening tumor. Despite some advances in traditional therapy, mortality and mobidity rates are high due to delayed diagnosis and ineffective treatment. Additionally, some patients inevitably suffer from various fatal adverse effects during the course of therapy. Therefore, it is imperative to develop novel methods to eradicate oral cancer cells with minimal adverse effects on normal cells. Nanotechnology is a promising and novel vehicle for the diagnosis and treatment of oral cancer with encouraging recent achievements. In this review, we present state-of-the-art nanotechnology-based drug delivery systems employed in the domain of oral cancer, especially for its enhanced diagnosis and therapy. We describe in detail the types of nanotechnology used in the management of oral cancer and summarize administration routes of nanodrugs. Finally, the potential and prospects of nanotechnology-based drug delivery systems as promising modalities of diagnosis and therapy of oral cancer are highlighted.

[Application of mixed reality in oromaxillofacial head and neck oncology surgery: a preliminary study].

Mixed reality (MR), characterized by the ability to integrate digital data into human real feeling, is a new technique in medical imaging and surgical navigation. MR has tremendous value in surgery, but its application in oromaxillofacial head and neck oncology surgery is not yet reported. This paper reports the application of MR in oromaxillofacial head and neck oncology surgery. The merits, demerits, and present research situations and prospects of MR are further discussed.

[Congenital infiltrating lipomatosis of face with seizures: a case report].

Congenital infiltrating lipomatosis of the face is a rare disorder resulting from overgrowth of adipose tissues. This condition presents gradually with swelling along with age, hypertrophy of adjacent bones, and tooth abnormalities. This study reports a case of congenital infiltrating lipomatosis of face with seizures and reviews relevant literature on the etiology, clinical symptom, diagnosis, and treatment of this condition.

Double-Layer Microsphere Incorporated with Strontium Doped Calcium Polyphosphate Scaffold for Bone Regeneration.

To design and prepare a novel controlled release system for sustained release of two drugs. In this study, a double-layer microsphere was incorporated with strontium-doped calcium polyphosphate (SCPP) scaffold to facilitate bone regeneration and achieve skull repair. The double-layer microsphere combining tetracycline loaded sodium alginate and matrix metalloproteinase-2 (MMP-2) loaded chitosan was manufactured by electrospinning, which were further adhered to SCPP scaffold. The characteristics of microstructure were observed through scanning electron microscope. Loading efficiencies and the optimal ratio of microsphere of the obtained controlled release system were investigated. In addition, the cytotoxicity and the effects on osteoblast proliferation and expressions of osteogenesis-related factors were examined in vitro. Thereafter, the compound material with the controlled release system was implanted in the skull defect of rabbit to evaluate its properties of promoting bone regeneration. The results indicated that this novel controlled release system with SCPP scaffold and the double-layer microspheres loaded with tetracycline and MMP-2 could be a promising material for bones repair.