Free buccal fat pad graft for the bone defect filling of medication-related osteonecrosis of the jaws: A novel surgical approach.

Surgical intervention for medication-related jaw osteonecrosis (MRONJ) is currently the main treatment method, offering a higher healing rate than conservative approaches. However, the management of bony defects after sequestrectomy remains a challenging issue due to poor vascularization from the drug effect. The use of pedicled buccal fat pad (PBFP) for filling bone defects has become common and effective but is limited to the posterior maxillary region. To add to the advantages of the buccal fat pad, we explored a novel treatment approach using a free buccal fat pad (FBFP) to fill bone defects other than the posterior maxilla. While the FBFP has been employed in oral defect reconstruction, currently published cases have been utilized in recipient sites with good blood supply. There has yet to be any usage in poor vascularization defects like MRONJ. This article describes that the FBFP was used to fill the surgical defects of 8 patients who were diagnosed with MRONJ and who underwent sequestrectomy and saucerization. During follow-up visits, there was excellent wound healing and no significant tissue depression. Based on successful treatment experiences, FBFP is a reliable therapeutic option for the management of poor vascularization defects like MRONJ treated through surgical intervention.

Enhancing surgical outcomes of posterior iliac bone harvesting through a pivotal modification.

Traditionally, patients are positioned in the prone position to access the donor site during the posterior iliac bone graft harvesting procedure. However, this well-established method is associated with complications such as pressure injuries, displacement of the endotracheal tube and intravenous catheter, and blindness. Moreover, the process of turning patients 180° between the supine and prone positions is both laborious and time consuming. However, no updates have been made in the approaches published in the literature to counteract these problems. Therefore, to overcome these challenges and improve patient outcomes, we proposed a pivotal modification: change prone position to the lateral decubitus position. This approach allowed us to effectively avoid the aforementioned complications. In addition, this modification offered significant advantages, including ease of implementation and timesaving benefits. The article presented results of the modification and a comprehensive evaluation of clinical and anesthetic considerations comparing the two methods.

Microbiome dysbiosis inhibits carcinogen-induced murine oral tumorigenesis.

Oral cancer is one of the most common cancers worldwide and ranks fourth for the mortality rate of cancers in males in Taiwan. The oral microbiota is the microbial community in the oral cavity, which is essential for maintaining oral health, but the relationship between oral tumorigenesis and the oral microbiota remains to be clarified. This study evaluated the effect of microbiome dysbiosis on oral carcinogenesis in mice, and the impact of the microbiome and its metabolic pathways on regulating oral carcinogenesis. We found that antibiotics treatment decreases carcinogen-induced oral epithelial malignant transformation. Microbiome analysis based on 16S rRNA gene sequencing revealed that the species richness of fecal specimens was significantly reduced in antibiotic-treated mice, while that in the salivary specimens was not decreased accordingly. Differences in bacterial composition, including Lactobacillus animalis abundance, in the salivary samples of cancer-bearing mice was dramatically decreased. L. animalis was the bacterial species that increased the most in the saliva of antibiotic-treated mice, suggesting that L. animalis may be negatively associated with oral carcinogenesis. In functional analysis, the microbiome in the saliva of the tumor-bearing group showed greater potential for polyamine biosynthesis. Immunochemical staining proved that spermine oxidase, an effective polyamine oxidase, was upregulated in mouse oral cancer lesions. In conclusion, oral microbiome dysbiosis may alter polyamine metabolic pathways and reduce carcinogen-induced malignant transformation of the oral epithelium.

Supercritical Carbon Dioxide Decellularized Xenograft-3D CAD/CAM Carved Bone Matrix Personalized for Human Bone Defect Repair.

About 30-50% of oral cancer patients require mandibulectomy and autologous fibula reconstruction. Autograft is the gold standard choice because of its histocompatibility; however, it requires additional surgery from the patient and with possible complications such as loss of fibula leading to calf weakening in the future. Allograft and xenograft are alternatives but are susceptible to immune response. Currently, no personalized bone xenografts are available in the market for large fascial bone defects. In addition, a large-sized complex shape bone graft cannot be produced directly from the raw material. We propose the use of porcine bones with 3D CAD/CAM carving to reconstruct a personalized, wide range and complex-shaped bone. We anticipate that patients can restore their native facial appearance after reconstruction surgery. Supercritical CO2 (SCCO2) technology was employed to remove the cells, fat and non-collagenous materials while maintaining a native collagen scaffold as a biomedical device for bone defects. We successfully developed 3D CAD/CAM carved bone matrices, followed by SCCO2 decellularization of those large-sized bones. A lock-and-key puzzle design was employed to fulfil a wide range of large and complex-shaped maxillofacial defects. To conclude, the 3D CAD/CAM carved bone matrices with lock and key puzzle Lego design were completely decellularized by SCCO2 extraction technology with intact natural collagen scaffold. In addition, the processed bone matrices were tested to show excellent cytocompatibility and mechanical stiffness. Thus, we can overcome the limitation of large size and complex shapes of xenograft availability. In addition, the 3D CAD/CAM carving process can provide personalized tailor-designed decellularized bone grafts for the native appearance for maxillofacial reconstruction surgery for oral cancer patients and trauma patients.

Epigenetic Deregulation of Protein Tyrosine Kinase 6 Promotes Carcinogenesis of Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) accounts for over 90% of oral cancers and causes considerable morbidity and mortality. Epigenetic deregulation is a common mechanism underlying carcinogenesis. DNA methylation deregulation is the epigenetic change observed during the transformation of normal cells to precancerous and eventually cancer cells. This study investigated the DNA methylation patterns of PTK6 during the development of OSCC. Bisulfite genomic DNA sequencing was performed to determine the PTK6 methylation level. OSCC animal models were established to examine changes in PTK6 expression in the different stages of OSCC development. The DNA methylation of PTK6 was decreased during the development of OSCC. The mRNA and protein expression of PTK6 was increased in OSCC cell lines compared with human normal oral keratinocytes. In mice, the methylation level of PTK6 decreased after treatment with 4-nitroquinoline 1-oxide and arecoline, and the mRNA and protein expression of PTK6 was increased. PTK6 hypomethylation can be a diagnostic marker of OSCC. Upregulation of PTK6 promoted the proliferation, migration, and invasion of OSCC cells. PTK6 promoted carcinogenesis and metastasis by increasing STAT3 phosphorylation and ZEB1 expression. The epigenetic deregulation of PTK6 can serve as a biomarker for the early detection of OSCC and as a treatment target.

Single-Cell RNA Sequencing Analysis for Oncogenic Mechanisms Underlying Oral Squamous Cell Carcinoma Carcinogenesis with Candida albicans Infection.

Oral squamous cell carcinoma (OSCC) carcinogenesis involves heterogeneous tumor cells, and the tumor microenvironment (TME) is highly complex with many different cell types. Cancer cell-TME interactions are crucial in OSCC progression. Candida albicans (C. albicans)-frequently pre-sent in the oral potentially malignant disorder (OPMD) lesions and OSCC tissues-promotes malignant transformation. The aim of the study is to verify the mechanisms underlying OSCC car-cinogenesis with C. albicans infection and identify the biomarker for the early detection of OSCC and as the treatment target. The single-cell RNA sequencing analysis (scRNA-seq) was performed to explore the cell subtypes in normal oral mucosa, OPMD, and OSCC tissues. The cell composi-tion changes and oncogenic mechanisms underlying OSCC carcinogenesis with C. albicans infec-tion were investigated. Gene Set Variation Analysis (GSVA) was used to survey the mechanisms underlying OSCC carcinogenesis with and without C. albicans infection. The results revealed spe-cific cell clusters contributing to OSCC carcinogenesis with and without C. albicans infection. The major mechanisms involved in OSCC carcinogenesis without C. albicans infection are the IL2/STAT5, TNFα/NFκB, and TGFß signaling pathways, whereas those involved in OSCC carcinogenesis with C. albicans infection are the KRAS signaling pathway and E2F target down-stream genes. Finally, stratifin (SFN) was validated to be a specific biomarker of OSCC with C. albicans infection. Thus, the detailed mechanism underlying OSCC carcinogenesis with C. albicans infection was determined and identified the treatment biomarker with potential precision medicine applications.

Evaluation of total bone and cortical bone thickness of the palate for temporary anchorage device insertion.

BACKGROUND/PURPOSE: The palate has become a popular site for the placement of temporary anchorage devices (TADs) owing to its bone quantity and quality. This study aimed to investigate total and cortical bone thicknesses in the whole palate as well as palatal width using a standard grid system and cone-bean computed tomography (CBCT) images. MATERIALS AND METHODS: The CBCT images of 43 samples were selected. The total bone and cortical bone thicknesses of the palate were surveyed on 64 points per patient. The palatal width was measured. The difference between the age and sex groups was analyzed. RESULTS: The total palatal bone thickness in the adult group ranged from 9.85 ±â€¯2.04 to 1.87 ±â€¯0.79 mm. In the adolescent group, we found one-third of the incisor roots in the area 3 mm distal to the incisive foramen and 8 mm lateral to the mid-palatal suture. The cortical bone thickness in adults was significantly thicker in the posterior paramedian area than that in adolescents. CONCLUSION: The thickest vertical bone is located in the zone 3 mm distal to the incisive foramen and 4-8 mm lateral to the midpalate. The zone 6 mm posterior to the incisive foramen and 2-8 mm lateral to the midpalate exhibited optimal thickness and was away from the incisor roots. This region could be a safe zone for adolescent patients to place TADs. When TADs are to be inserted at the posterior palate, the 2-mm paramedian area should be the first region of choice.

Evaluating the bone-regenerative role of the decellularized porcine bone xenograft in a canine extraction socket model.

OBJECTIVE: To evaluate the efficacy of a novel decellularized porcine bone xenograft, produced by supercritical carbon dioxide extraction technology, on alveolar socket healing after tooth extraction compared to a commercially available deproteinized bovine bone (Bio-Oss®). MATERIALS AND METHODS: Nine dogs (about 18 months old and weighing between 20 kg and 30 kg) underwent extractions of lower second to fourth premolars, bilaterally. The dogs were randomly selected and allocated to the following groups: Group 1: control unfilled socket; Group 2: socket filled with decellularized porcine bone xenograft (ABCcolla®) and covered by a commercially available porcine collagen membrane (Bio-Gide®); Group 3: socket filled with Bio-Oss® and covered by Bio-Gide® membrane. One dogs from each group was sacrificed at 4-, 12-, and 24-week to evaluate the socket healing after tooth extraction. The mandible bone blocks were processed without decalcification and specimens were embedded in methyl methacrylate and subjected to histopathology analyses to evaluate the bone regeneration in the extraction sockets. RESULTS: At 24-week after socket healing, ABCcolla® treated defects demonstrated significantly higher histopathology score in new bone formation and bone bridging, but significantly lower score in fluorescent labeling than those of the Bio-Oss®. In the microphotographic examination, decellularized porcine bone xenograft showed similar characteristics of new bone formation to that of Bio-Oss®. However, there was significantly less remnant implant materials in the decellularized porcine bone xenograft compared to the Bio-Oss® group at 24-week. Thus, the decellularized porcine bone graft seems to have promising bone regeneration properties similar to that of Bio-Oss® with less remnant grafted material in a canine tooth extraction socket model. CONCLUSIONS: Within the limits of the study, we concluded that ABCcolla® treated defects demonstrated significantly more new bone formation and better bone bridging, but less amount of fluorescent labeling than those of the Bio-Oss® group. However, clinical studies in humans are recommended to confirm these findings.

Unusual Supernumerary Teeth and Treatment Outcomes Analyzed for Developing Improved Diagnosis and Management Plans.

PURPOSE: Supernumerary teeth (SNTs) are teeth or tooth-like structures that have erupted or might erupt in addition to the 20 primary or 32 permanent teeth. The simultaneous presentation of multiple SNTs, syndrome-related multiple SNTs, SNTs inside the maxillary sinus and treatment outcomes were analyzed to develop improved diagnosis and management plans. PATIENTS AND METHODS: This retrospective study reviewed the medical records of National Cheng Kung University Hospital patients who had undergone surgical intervention with general anesthesia between February 2014 and September 2018; analyzed panoramic radiographs and cone beam computed tomography scans of their multiple SNTs; and used descriptive statistics to discuss treatments and relative complications, especially of unusual SNTs. RESULTS: The records of 165 patients (127 male and 38 female patients; mean age, 12.4 years) with 241 SNTs (120 patients had 1 SNT, 35 had 2 SNTs, 3 had 3 SNTs, 2 had 4 SNTs, 2 had 5 SNTs, 2 had 6 SNTs, and 1 had 12 SNTs) were reviewed. There were 185 SNTs in the maxilla and 56 in the mandible; 153 were mesiodens and 115 were inverted; 142 were asymptomatic and 137 were conical; and 228 were fully impacted and 210 were partial roots. Two patients had SNTs inside the maxillary sinus, and one had 5 SNTs and Marfan syndrome. Two patients had postoperative lip or chin paresthesia, and two had postoperative sinusitis. CONCLUSIONS: Patient demographic variables provided useful epidemiologic information. We recommend panoramic radiographs or cone beam computed tomography for managing patients with possible multiple SNTs and for extracting SNTs.

Growth-regulated oncogene-α from oral submucous fibrosis fibroblasts promotes malignant transformation of oral precancerous cells.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a common human malignancy and is usually preceded by the oral precancerous lesions. Oral submucous fibrosis (OSF) is one of the oral precancerous lesions with high incidence of malignant transformation. In addition to cancer cells, cancer-associated fibroblasts in the tumor microenvironment are correlated with cancer progression, but the role of fibroblasts from OSF in tumorigenesis and progression is still unknown. Growth-regulated oncogene-α (GRO-α), a member of CXC chemokine family, is related to tumorigenesis in several cancers. In this study, we would like to explore the role of GRO-α from OSF-associated fibroblasts in oral cancer progression. METHODS: We isolated primary culture fibroblasts of normal, precancerous, and tumor tissues from patients with OSCC accompanied with OSF. A cytokine array was used to screen cytokine secretions in the conditioned media of the fibroblasts. A wound healing migration assay, WST-1 cell proliferation assay, rhodamine-phalloidin staining, and soft agar colony formation assay were used to investigate the effects of GRO-α on a dysplastic oral keratinocyte cell line (DOK) cell migration, growth, and anchorage-independent growth. RESULTS: GRO-α was identified to be increased in conditioned media of OSF-associated fibroblasts. GRO-α promotes DOK cells proliferation, migration, and anchorage-independent growth through enhancing the EGFR/ERK signaling pathway, F-actin rearrangement, and stemness properties, respectively. Moreover, GRO-α neutralizing antibodies downregulated the conditioned medium-induced cell proliferation and migration of DOK. CONCLUSION: GRO-α from OSF-associated fibroblasts paracrinally promotes oral malignant transformation and significantly contributes to OSCC development.

Outcome Analysis and Unexpected-Scenario Prediction in 2-Stage Orthodontic Lower Third Molar Extraction.

PURPOSE: We propose a 2-stage orthodontic lower third molar extraction procedure to reduce iatrogenic inferior alveolar nerve injury. We tested our hypothesis that there are factors that can predict both dislodgement of the root portion and limited traction distances. PATIENTS AND METHODS: Fifteen patients (mean age, 25.7 years; age range, 17 to 65 years) with 20 lower third molars were enrolled. Panoramic films and cone beam computed tomography were analyzed. Dislodgement of the root portion, traction distance, duration of the orthodontic phase, and postoperative complications were documented. The predictive factors were analyzed and discussed. RESULTS: Three teeth had dislodgements of the root portion. The mean traction duration was 59.2 days (range, 33 to 77 days), and the mean traction distance was 2.60 mm (range, 0.27 to 5.20 mm). Root apex cortical bone indentation and root curvature were significantly associated with traction distance. Pulpitis symptoms were documented in 1 tooth, and no postoperative nerve disturbances occurred. CONCLUSIONS: Our proposed 2-stage orthodontic lower third molar extraction procedure reduced iatrogenic inferior alveolar nerve injury. Cortical bone indentation and root curvature predicted dislodgement of the root portion and limited traction distances.