An 84-Year-Old Man with a History of Myeloma and Biphosphonate-Related Osteonecrosis of the Jaw Treated with Preoperative Vascular Embolization Before Partial Maxillectomy.

BACKGROUND Bisphosphonates and anti-receptor activator of nuclear factor kappa B antibodies are used to treat bone diseases associated with increased osteoclast activity, including myeloma. However, they can cause osteonecrosis of the jaw, known as medication-related osteonecrosis of the jaw. This report presents a case of a patient with a history of myeloma who required posterior maxilla resection for bisphosphonate-related osteonecrosis of the jaw, in which preoperative embolization prevented unexpected bleeding related to vascular injury and allowed for a safe procedure with minimal bleeding. CASE REPORT An 84-year-old man presented to our department with a 3-year history of purulent drainage and bone exposure in the right maxilla. Based on the clinical findings at the initial visit, the clinical diagnosis was bisphosphonate-related osteonecrosis of the jaw, and the patient underwent a partial right maxillary osteotomy. This surgery was associated with a risk of unexpected bleeding from a branch of the maxillary artery during the posterior maxilla resection. A catheter-based embolization of the maxillary artery was performed the day before performing a partial maxillectomy to avoid unexpected bleeding risk. Thus, no abnormal bleeding occurred during partial maxillectomy, and no postoperative complications occurred for 3 years. CONCLUSIONS In the surgical treatment of medication-related osteonecrosis of the jaw, preoperative vascular embolization of the peripheral maxillary artery beyond the middle meningeal artery bifurcation is a valuable technique for safe maxillectomy involving the posterior maxilla.

Preoperative endovascular arterial embolization to avoid maxillary artery injury in maxillary gingival cancer surgery.

For maxillary gingival carcinomas, especially those in the molar region, surgical resection is often performed beyond the maxillary tuberosity. Bleeding from the posterior superior alveolar or maxillary artery into the pterygoid process is difficult to stop during partial maxillary resection. Advances in catheterization and materials have enabled the embolization of various vessels. In this report, we describe two cases of maxillary gingival cancer in which preoperative endovascular arterial embolization prevented bleeding due to unexpected vascular injury, allowing for a safe surgery with minimal blood loss. This technique effectively avoids emergency hemostasis for unexpected bleeding when resecting gingival cancers in the maxillary molar region.

Scaffold-free bone-like 3D structure established through osteogenic differentiation from human gingiva-derived stem cells.

Introduction & objectives: Stem cell therapy for regenerative medicine has been sincerely investigated, but not still popular although some clinical trials show hopeful results. This therapy is suggested to be a representative candidate such as bone defect due to the accident, iatrogenic resection oncological tumor, congenital disease, and severe periodontitis in oral region. Recently, the Bio-3D printer "Regenova®" has been introduced as an innovative three-dimensional culture system, equipped scaffold-free bio-assembling techniques without any biomaterials. Therefore, we expected a mount of bone defect could be repaired by the structure established from this Bio-3D printer using osteogenic potential stem cells. Material & methods: The gingival tissue (1x1 mm) was removed from the distal part of the lower wisdom tooth of the patients who agreed our study. Human Gingival Mesenchymal Stem Cells (hGMSCs) were isolated from this tissue and cultured, since we confirmed the characteristics such as facile isolation and accelerated proliferation, further, strong potential of osteogenic-differentiation. Spheroids were formed using hGMSC in 96-well plates designed for low cell adhesion. The size of the spheroids was measured, and fluorescent immunostaining was employed to verify the expression of stem cell and apoptosis marker, and extracellular matrix. Following four weeks of bone differentiation, µCT imaging was performed. Calcification was confirmed by alizarin red and von Kossa staining. Fluorescent immunostaining was utilized to assess the expression of markers indicative of advanced bone differentiation. Results: We have established and confirmed the spheroids (∼600 µm in diameter) constructed from human GMSCs (hGMSCs) still maintain stem cell potentials and osteogenic differentiation abilities from the results that CD73 and not CD34 were expressed as stem cell positive and negative marker, respectively. These spheroids were pilled up like cylindal shape to the "Kenzan" platform of Bio-3D printer and cultured for 7days. The cylindal structure originated from compound spheroids were tried to differentiate into bone four weeks with osteogenic induction medium. The calcification of bio-3D printed bone-like structures was confirmed by alizarin red and Von Kossa staining. In addition, µCT analysis revealed that the HU (Hounsfield Unit) of the calcified structures was almost identical to that of trabecular bone. Immunofluorescent staining detected osteocalcin expression, a late-stage bone differentiation marker. Conclusion: For the first time, we have achieved the construction of a scaffold-free, bone-like luminal structure through the assembly of spheroids comprised of this hGMSCs. This success is sure to be close to the induction of clinical application against regenerative medicine especially for bone defect disease.

Luteolin Is a Potential Immunomodulating Natural Compound against Pulpal Inflammation.

Aim: The present study evaluated the therapeutic effects of luteolin in alleviating pulpitis of dental pulp- (DP-) derived microvesicles (MVs) via the inhibition of protein kinase R- (PKR-) mediated inflammation. Methodology. Proteomic analysis of immortalized human dental pulp (DP-1) cell-derived MVs was performed to identify PKR-associated molecules. The effect of luteolin on PKR phosphorylation in DP-1 cells and the expression of tumor necrosis factor-α (TNF-α) in THP-1 macrophage-like cells were validated. The effect of luteolin on cell proliferation was compared with that of chemical PKR inhibitors (C16 and 2-AP) and the unique commercially available sedative guaiacol-parachlorophenol. In the dog experimental pulpitis model, the pulps were treated with (1) saline, (2) guaiacol-parachlorophenol, and (3) luteolin. Sixteen teeth from four dogs were extracted, and the pulp tissues were analyzed using hematoxylin and eosin staining. Immunohistochemical staining was performed to analyze the expression of phosphorylated PKR (pPKR), myeloperoxidase (MPO), and CD68. Experimental endodontic-periodontal complex lesions were established in mouse molar through a silk ligature and simultaneous MV injection. MVs were prepared from DP-1 cells with or without pretreatment with 2-AP or luteolin. A three-dimensional microcomputed tomography analysis was performed on day 7 (n = 6). Periodontal bone resorption volumes were calculated for each group (nonligated-ligated), and the ratio of bone volume to tissue volume was measured. Results: Proteomic analysis identified an endogenous PKR activator, and a protein activator of interferon-induced PKR, also known as PACT, was included in MVs. Luteolin inhibited the expressions of pPKR in DP-1 cells and TNF-α in THP-1 cells with the lowest suppression of cell proliferation. In the dog model of experimental pulpitis, luteolin treatment suppressed the expression of pPKR-, MPO-, and CD68-positive cells in pulp tissues, whereas guaiacol-parachlorophenol treatment caused coagulative necrosis and disruption. In a mouse model of endodontic-periodontal complex lesions, luteolin treatment significantly decreased MV-induced alveolar bone resorption. Conclusion: Luteolin is an effective and safe compound that inhibits PKR activation in DP-derived MVs, enabling pulp preservation.

A Case of a Dentigerous Cyst in the Maxillary Sinus Treated Preoperatively With Vascular Embolization to Avoid Intraoperative Abnormal Bleeding.

Bone cysts involving the maxillary sinus are frequently observed, and controlling bleeding from the maxillary or posterior superior alveolar arteries is extremely difficult when the surgical site extends into the palatine fossa or the wing socket behind the maxillary sinus. In this report, we describe a case wherein preoperative endovascular arterial embolization prevented bleeding owing to an unexpected vascular injury that occurred during the removal of a dentigerous cyst from the maxillary sinus. This resulted in a safe operation with less intraoperative bleeding. Although this approach carries the risk of complications, such as paralysis, around the affected area, the likelihood of such complications is low. This approach is useful for performing a safe surgery with minimal blood loss because it avoids the need for emergency hemostasis for major intraoperative hemorrhage.

Epithelial-to-mesenchymal transition, inflammation, subsequent collagen production, and reduced proteinase expression cooperatively contribute to cyclosporin-A-induced gingival overgrowth development.

Drug-induced gingival overgrowth (DIGO), induced by certain immunosuppressive drugs, antihypertensive agents, and antiepileptic drugs, may contribute to the formation of deeper periodontal pockets and intractableness in periodontitis. To date, multiple factors such as enhanced matrix production, inflammation, and reduced matrix degradation might be involved in the pathogenesis of DIGO. We have previously reported that SPOCK-1, a heparan sulfate proteoglycan, could affect gingival thickening by promoting epithelial-to-mesenchymal transition (EMT) in gingival keratinocytes. However, few studies have investigated whether a combination of these factors enhances the DIGO phenotype in animal models. Therefore, we investigated whether SPOCK-1, periodontal inflammation, and cyclosporin-A (CsA) could cooperatively promote gingival overgrowth. We first confirmed that Spock-1 overexpressing (Spock1-Tg) mice showed significantly thicker gingiva and greater alveolar bone loss than WT mice in response to ligature-induced experimental periodontitis. DIGO was induced by the combination of CsA administration and experimental periodontitis was significantly enhanced in Spock1-Tg mice compared to that in WT mice. Ligature-induced alveolar bone loss in CsA-treated Spock1-Tg mice was also significantly greater than that in CsA-treated WT mice, while being accompanied by an increase in Rankl and Col1a1 levels and a reduction in matrix metalloprotease expression. Lastly, SPOCK-1 promoted RANKL-induced osteoclast differentiation in both human peripheral blood mononuclear cells and murine macrophages, while peritoneal macrophages from Spock1-Tg mice showed less TNFα and IL-1ß secretion than WT mice in response to Escherichia coli lipopolysaccharide. These results suggest that EMT, periodontal inflammation, and subsequent enhanced collagen production and reduced proteinase production contribute to CsA-induced DIGO pathogenesis.