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BACKGROUND/PURPOSE: Zirconia has been a popular material in dental implantology with good biocompatibility. But few research focused on its application in implant drills. This study aimed to investigate the physical, thermal, and biological effects on using the zirconia and stainless-steel drills for implant bone site preparation. METHODS: We performed a series of experiments to evaluate the physical wearing properties of zirconia and stainless-steel drills of identical diameter and similar shape. During the implant site preparation thermal test, we subjected both drills onto a resin-embedded bone, utilizing a thermal couple device without irrigation. Moreover, we conducted a cell study by collecting bone cells in vivo while preparing the implant site with both tested drills. The cell activity was evaluated through cell proliferation colorimetric analysis (XTT) and alkaline phosphatase (ALP) activity measurements. RESULTS: The zirconia drill outperforms the stainless-steel drill in terms of requiring less force, maintaining stability over repeated cutting tests, and generating lower temperatures during drilling (stainless-steel drill: 45.48 ± 1.31 °C; zirconia-coated drill: 32.98 ± 1.21 °C, P = 0.000247). Meanwhile, both types of drills show similar results in XTT colorimetric analysis and ALP activity test. CONCLUSION: The thermal effect study is more favorable for using the zirconia drill than the stainless-steel drill for bone preparation. Cytological analysis indicate that the zirconia drill produces a similar impact on bone cells activity as the stainless-steel drill. Therefore, we conclude that the zirconia drills offer a good cutting effect similar to currently available stainless-steel drills in various aspects.
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AIM: Biallelic loss-of-function FAM20A mutations cause amelogenesis imperfecta (AI) type IG, better known as enamel renal syndrome (ERS), characterized by severe enamel hypoplasia, delayed/failed tooth eruption, intrapulpal calcifications, gingival hyperplasia and nephrocalcinosis. FAM20A binds to FAM20C, the Golgi casein kinase (GCK) and potentiates its function to phosphorylate secreted proteins critical for biomineralization. While many FAM20A pathogenic mutations have been reported, the pathogeneses of orodental anomalies in ERS remain to be elucidated. This study aimed to identify disease-causing mutations for patients with ERS phenotypes and to discern the molecular mechanism underlying ERS intrapulpal calcifications. METHODOLOGY: Phenotypic characterization and whole exome analyses were conducted for 8 families and 2 sporadic cases with hypoplastic AI. A minigene assay was performed to investigate the molecular consequences of a FAM20A splice-site variant. RNA sequencing followed by transcription profiling and gene ontology (GO) analyses were carried out for dental pulp tissues of ERS and the control. RESULTS: Biallelic FAM20A mutations were demonstrated for each affected individual, including 7 novel pathogenic variants: c.590-5T>A, c.625T>A (p.Cys209Ser), c.771del (p.Gln258Argfs*28), c.832_835delinsTGTCCGACGGTGTCCGACGGTGTC CA (p.Val278Cysfs*29), c.1232G>A (p.Arg411Gln), c.1297A>G (p.Arg433Gly) and c.1351del (p.Gln451Serfs*4). The c.590-5T>A splice-site mutation caused Exon 3 skipping, which resulted in an in-frame deletion of a unique region of the FAM20A protein, p.(Asp197_Ile214delinsVal). Analyses of differentially expressed genes in ERS pulp tissues demonstrated that genes involved in biomineralization, particularly dentinogenesis, were significantly upregulated, such as DSPP, MMP9, MMP20 and WNT10A. Enrichment analyses indicated overrepresentation of gene sets associated with BMP and SMAD signalling pathways. In contrast, GO terms related to inflammation and axon development were underrepresented. Among BMP signalling genes, BMP agonists GDF7, GDF15, BMP3, BMP8A, BMP8B, BMP4 and BMP6 were upregulated, while BMP antagonists GREM1, BMPER and VWC2 showed decreased expression in ERS dental pulp tissues. CONCLUSIONS: Upregulation of BMP signalling underlies intrapulpal calcifications in ERS. FAM20A plays an essential role in pulp tissue homeostasis and prevention of ectopic mineralization in soft tissues. This critical function probably depends upon MGP (matrix Gla protein), a potent mineralization inhibitor that must be properly phosphorylated by FAM20A-FAM20C kinase complex.
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Amelogénesis Imperfecta , Calcinosis , Proteínas del Esmalte Dental , Nefrocalcinosis , Humanos , Nefrocalcinosis/genética , Nefrocalcinosis/patología , Amelogénesis Imperfecta/genética , Amelogénesis Imperfecta/metabolismo , Amelogénesis Imperfecta/patología , Pulpa Dental/metabolismo , Proteínas del Esmalte Dental/genética , Mutación , Perfilación de la Expresión Génica , Proteínas Portadoras/genéticaRESUMEN
STATEMENT OF PROBLEM: Progressive peri-implant marginal bone loss and peri-implantitis have become a growing problem, but cross-sectional studies on their prevalence and risk factors are sparse. PURPOSE: The purpose of this cross-sectional clinical study was to investigate the prevalence of peri-implant marginal bone loss (MBL) and to identify systemic and local risk factors. MATERIAL AND METHODS: All adult patients who had received dental implants at the National Taiwan University Hospital (NTUH) during 2009 or 2010 were included. Their medical records were collected from the NTUH-integrative Medical Database. Consecutive follow-up radiographs were accessed for severity of MBL. The influence of each factor on MBL was estimated by using generalized estimating equations (GEEs). RESULTS: A total of 732 participants with 1873 implants were analyzed (mean follow-up: 5.30 years). The prevalence of MBL was 59.15% at the individual level and 49.55% at the implant level. The risk indicators identified for the presence of MBL were follow-up period of more than 2 years, diagnosis of diabetes within 12 months, radiation therapy (2 years after implant placement), implant location at maxillary canine (compared with mandibular molar), and implants from the Nobel Biocare brands (Brånemark System and NobelActive). A second multivariate GEE model confirmed the association of progressive MBL with implant location at the maxillary canine and mandibular incisor and implant brand or design. CONCLUSIONS: The identified risk indicators for MBL were longer follow-up period, diagnosis of diabetes, radiation therapy, implant location at maxillary canine, and implant brand or design.
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In this study, we fabricated gelatin/nano-hydroxyapatite/metformin scaffold (GHMS) and compared its effectiveness in bone regeneration with extraction-only, Sinbone, and Bio-Oss Collagen® groups in a critical size rat alveolar bone defect model. GHMS was synthesized by co-precipitating calcium hydroxide and orthophosphoric acid within gelatin solution, incorporating metformin, and cross-linked by microbial transglutaminase. The morphology, characterization, and biocompatibility of scaffold were examined. The in vitro effects of GHMS on osteogenic gene and protein expressions were evaluated. In vivo bone formation was assessed in a critical size rat alveolar bone defect model with micro-computed tomography and histological examination by comparing GHMS with extraction-only, Sinbone, and Bio-Oss Collagen®. The synthesized GHMS had a highly interconnected porous structure with a mean pore size of 81.85 ± 13.8 µm. GHMS exhibited good biocompatibility; promoted ALPL, RUNX2, SP7, BGLAP, SPARC and Col1a1 gene expressions; and upregulated the synthesis of osteogenic proteins, including osteonectin, osteocalcin, and collagen type I. In critical size rat alveolar bone defects, GHMS showed superior bone regeneration compared to extraction-only, Sinbone, and Bio-Oss Collagen® groups as manifested by greater alveolar ridge preservation, while more bone formation with a lower percentage of connective tissue and residual scaffold at the defect sites grafted with GHMS in histological staining. The GHMS presented in this study may be used as a potential bone substitute to regenerate alveolar bone. The good biocompatibility, relatively fast degradation, interconnected pores allowing vascularization, and higher bioactivity properties of the components of the GHMS (gelatin, nHA, and metformin) may contribute to direct osteogenesis.
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Regeneración Ósea , Durapatita , Gelatina , Regeneración Tisular Dirigida , Metformina/administración & dosificación , Nanocompuestos , Andamios del Tejido , Animales , Materiales Biocompatibles/química , Biomarcadores , Fenómenos Químicos , Durapatita/química , Gelatina/química , Regeneración Tisular Dirigida/métodos , Inmunohistoquímica , Minerales , Modelos Animales , Nanocompuestos/química , Nanocompuestos/ultraestructura , Osteogénesis/efectos de los fármacos , Osteogénesis/genética , Ratas , Ingeniería de Tejidos , Andamios del Tejido/química , Microtomografía por Rayos XRESUMEN
This report provides three-phase concept for treating skeletal Class III growing patients with severe space deficiency. Three cases are presented. All had received miniplate-anchored facemask treatment and followed till near completion of growth. Infrazygomatic miniplates were used for both facemask protraction and distalization of the dentition to relieve crowding. With the aid of bone-anchored facemask, maxillary protraction may be continued independent of the orthodontic tooth movement even in late postpubertal growth peak stage. With cephalometric superimpositions using the structural method, we have demonstrated how vertical dental change could affect the skeletal changes and overall clinical outcomes. The persistent mandibular growth during pubertal growth spurt plays a main role in decreasing the effects of maxillary protraction. To keep up with the mandibular growth, we recommend using skeletally anchored facemask long-term till the end of growth spurt. Applying maxillary protraction from infrazygomatic miniplates exposed at the molar area has the merits that it avoids unwanted palatal rotation and that the miniplates maybe used as orthodontic anchorage when indicated. We emphasize the importance of planning the treatment contemplating the skeletal developmental stage and the completion of dental arches. This prolonged orthopedic treatment may contribute to greater long-term effects and stability.
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Aparatos de Tracción Extraoral , Maloclusión de Angle Clase III/terapia , Diseño de Aparato Ortodóncico , Técnicas de Movimiento Dental/instrumentación , Cefalometría/métodos , Niño , Femenino , Humanos , Masculino , Mandíbula/patología , Maxilar/patología , Diente Molar/patología , Métodos de Anclaje en Ortodoncia/instrumentaciónRESUMEN
BACKGROUND AND OBJECTIVE: Biallelic loss-of-function mutations of human FAM20A have been known to cause enamel-renal syndrome (ERS), featured by agenesis of dental enamel, nephrocalcinosis, and other orodental abnormalities, including gingival hyperplasia. However, while the histopathology of this gingival anomaly has been analyzed, its underlying molecular mechanism remains largely unknown. This study aimed to unravel the pathogenesis of gingival hyperplasia in ERS. METHODS: Whole-exome sequencing was conducted for an ERS case. Transcriptome analyses, using RNA sequencing, of the patient's gingiva were performed to unravel dysregulated molecules and aberrant biological processes underlying the gingival pathology of ERS, which was further confirmed by histology and immunohistochemistry. RESULTS: Two novel frameshift FAM20A mutations in Exon 1 (g.5417delG; c.129delG; p.Cys44Alafs*101) and Exon 5 (g.62248_62249delAG; c.734_735delAG; p.Glu245Glyfs*11) were identified. Transcriptional profiling of patient's gingival tissue revealed a total of 1683 genes whose expression had increased (1129 genes) or decreased (554 genes) at least 2-fold compared to control gingival tissues. There were 951 gene ontology (GO) terms of biological process being significantly over-represented or under-represented. While GOs involved in extracellular matrix organization, angiogenesis, biomineralization, and epithelial cell proliferation appeared to be activated in ERS gingiva, genes related to keratinocyte differentiation, epithelial development, and keratinization were of decreased expression. FAM20A immunohistochemistry revealed a strong reactivity at the suprabasal layers of epithelium in control gingiva but showed a significantly diminished and scattered signal in ERS tissues. For genes showing significant over-expression in the transcriptome analyses, namely ALPL, SPARC, and ACTA2, an increased immunoreactivity was observed. CONCLUSION: Our results unraveled a potential role for FAM20A in homeostasis of both gingival epithelium and connective tissues.
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Amelogénesis Imperfecta/genética , Proteínas del Esmalte Dental/genética , Encía/metabolismo , Nefrocalcinosis/genética , Transcriptoma , Adulto , Mutación del Sistema de Lectura , Perfilación de la Expresión Génica , Humanos , MasculinoRESUMEN
BACKGROUND/PURPOSE: Extraction of the third molar may cause post-operative complications. This study assessed whether application of pure type-1 collagen to the third molar extraction socket can reduce post-operative pain score and duration and promote socket bone healing. METHODS: Fourteen patients who underwent 20 bilateral and symmetric third molar extractions were included in this study. After two tooth extractions at two different occasions in the same patient, one socket was filled with pure type-1 collagen (experimental group, n = 20) and the other socket received nothing but the blood clot (control group, n = 20). The post-operative pain score and duration, mouth-opening limitation, and the bone density at the socket site were assessed at weeks 1, 2, 4, and 8 after tooth extraction. RESULTS: Patients in the experimental group had a significantly lower mean post-operative pain score (2.6 ± 1.2) than patients in the control group (4.7 ± 2.0), and had a significantly shorter post-operative pain duration (2.7 ± 1.4 days) than patients in the control group (3.7 ± 1.8 days). We also observed a significantly lower frequency of mouth-opening limitation in 20 experimental-group patients (45%) than in 20 control-group patients (90%, P = 0.007). Moreover, a significantly higher mineralization ratio (10.2%) was found in the experimental socket site than in the control socket site. CONCLUSION: Application of pure type-1 collagen to the third molar extraction socket can reduce post-operative pain score and duration, decrease the frequency of mouth-opening limitation, and increase mineralization ratio at the extraction socket site.
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Materiales Biocompatibles/administración & dosificación , Colágeno Tipo I/administración & dosificación , Tercer Molar/cirugía , Dolor Postoperatorio/prevención & control , Extracción Dental/efectos adversos , Adolescente , Adulto , Femenino , Humanos , Masculino , Mandíbula/cirugía , Complicaciones Posoperatorias/prevención & control , Estudios Retrospectivos , Taiwán , Diente Impactado/cirugía , Técnicas de Cierre de Heridas , Cicatrización de Heridas , Adulto JovenRESUMEN
BACKGROUND/PURPOSE: This study aimed at comparing the transverse and sagittal angulations of proximal segment after sagittal split ramus osteotomy (SSRO) and intraoral vertical ramus osteotomy (IVRO), and examining their influences on the stability of distal segment. METHODS: Patients who received SSRO (n = 21) or IVRO (n = 11) for mandibular setback were included. Lateral and posteroanterior cephalograms taken within 1 month before surgery (T1), within 1 week after surgery (T2), and at least 6 months after surgery (T3) were analyzed. The angulation of each proximal segment relative to the upper orbital margin line was measured on posteroanterior cephalogram and the sum of both angles (total ramus angle, TRA) was obtained. On lateral radiograph, ramus inclination angle (RIA) relative to a horizontal reference line 7° to the sella-nasion was assessed and B-point position was measured. RESULTS: From T1 to T2, more increases in TRA and RIA were noted after IVRO than after SSRO. From T2 to T3, TRA and RIA significantly decreased in IVRO group but remained relatively stable in SSRO group. ΔTRA(T1-T2) positively related to upward rotation of distal segment for SSRO and downward rotation for IVRO from T2 to T3. For SSRO only, ΔRIA(T1-T2) significantly related to forward movement of distal segment during remodeling. CONCLUSION: TRA and RIA increase significantly after IVRO and then regress, whereas they increase mildly after SSRO and remain stable. Increase in TRA significantly relates to distal segment rotation during remodeling for both surgeries, but increase in RIA relates to forward relapse of the distal segment only for SSRO. The reasons underlying the correlations are not certain and deserve future investigations.
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Mandíbula/cirugía , Osteotomía/métodos , Prognatismo/cirugía , Adolescente , Adulto , Femenino , Humanos , Masculino , Mandíbula/diagnóstico por imagen , Persona de Mediana Edad , Prognatismo/diagnóstico por imagen , RadiografíaRESUMEN
INTRODUCTION: We have previously demonstrated that auxiliary metformin therapy promotes healing of apical periodontitis. Here we aimed to investigate the effects of metformin on osteoblast differentiation and osteoclast formation in cultured cells and rat apical periodontitis. METHODS: Murine pre-osteoblasts MC3T3-E1 and macrophages RAW264.7 were cultured under hypoxia (2% oxygen) or normoxia (21% oxygen) and stimulated with receptor activator of nuclear factor-κB ligand (RANKL) when indicated. Metformin was added to the cultures to evaluate its anti-hypoxic effects. Expressions of osteoblast differentiation regulator runt-related transcription factor 2 (RUNX2), RANKL, and osteoclast marker tartrate-resistant acid phosphatase (TRAP) were assessed by Western blot. Apical periodontitis was induced in mandibular first molars of 10 Sprague-Dawley rats. Root canal therapy with or without metformin supplement was performed. Periapical bone resorption was measured by micro-computed tomography. Immunohistochemistry was used to examine RUNX2, RANKL, and TRAP expressions. RESULTS: Hypoxia suppressed RUNX2 expression and enhanced RANKL synthesis in pre-osteoblasts. TRAP production increased in macrophages after hypoxia and/or RANKL stimulation. Metformin reversed hypoxia-induced RUNX2 suppression and RANKL synthesis in pre-osteoblasts. Metformin also inhibited hypoxia and RANKL-enhanced TRAP synthesis in macrophages. Intracanal metformin diminished bone loss in rat apical periodontitis. Comparing with vehicle control, cells lining bone surfaces in metformin-treated lesions had significantly stronger expression of RUNX2 and decreased synthesis of RANKL and TRAP. CONCLUSIONS: Alleviation of bone resorption by intracanal metformin was associated with enhanced osteoblast differentiation and diminished osteoclast formation in rat apical periodontitis. Our results endorsed the role of metformin as an effective medicament for inflammatory bone diseases.
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Resorción Ósea , Metformina , Periodontitis Periapical , Ratas , Ratones , Animales , Osteoclastos , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Metformina/farmacología , Metformina/uso terapéutico , Microtomografía por Rayos X , Ratas Sprague-Dawley , Resorción Ósea/metabolismo , Osteoblastos , Periodontitis Periapical/patología , Diferenciación Celular , Hipoxia/metabolismo , Oxígeno/metabolismo , Ligando RANK/metabolismoRESUMEN
Current rat alveolar ridge preservation models have not been well standardized. In this study, we proposed decoronation-induced infected alveolar socket model of rat. The bilateral maxillary first molars (M1) of twenty-four rats were decoronized or extracted. After 2, 6, 10, and 14 weeks, bone and soft tissue changes at M1 and periodontal conditions of maxillary second (M2) and third molars (M3) were evaluated by micro-computed tomography and histological analysis. Additional eighteen rats with standardized size defects were grafted with Bio-Oss Collagen to compare with unmanipulated contralateral side. Decoronation preserved greater bone and soft tissue dimensions at M1, provided larger three-dimensional (3D) bone contour volume, but also promoted periodontal breakdown of M2 Histological results showed intense inflammatory cell infiltrations and severe bone resorption within M1 socket and at mesial aspect of M2. The critical dimensions to accommodate largest standardized defect at M1 were 2.2-2.3 mm at vertical bone height and 2.8-3.2 mm at alveolar crestal width. Bio-Oss Collagen could not fully preserve buccal or palatal bone height but could be beneficial in preserving ridge width in large alveolar defects. Collectively, if periodontally-involved alveolar bone defect is preferred, we suggest extracting M1 roots 6 weeks after decoronation to allow periodontitis to occur at M2. If standardized critical dimension defect is preferred, we suggest extracting M1 roots 2 weeks after decoronation, and creating defect in the middle of M1 site with size no larger than 2.7 mm diameter to its full depth.
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Pérdida de Hueso Alveolar , Proceso Alveolar , Alveolo Dental , Pérdida de Hueso Alveolar/diagnóstico por imagen , Pérdida de Hueso Alveolar/etiología , Pérdida de Hueso Alveolar/patología , Proceso Alveolar/diagnóstico por imagen , Proceso Alveolar/patología , Animales , Colágeno/uso terapéutico , Minerales , Ligamento Periodontal/patología , Ratas , Extracción Dental , Microtomografía por Rayos XRESUMEN
Accurate bone segmentation and anatomical landmark localization are essential tasks in computer-aided surgical simulation for patients with craniomaxillofacial (CMF) deformities. To leverage the complementarity between the two tasks, we propose an efficient end-to-end deep network, i.e., multi-task dynamic transformer network (DTNet), to concurrently segment CMF bones and localize large-scale landmarks in one-pass from large volumes of cone-beam computed tomography (CBCT) data. Our DTNet was evaluated quantitatively using CBCTs of patients with CMF deformities. The results demonstrated that our method outperforms the other state-of-the-art methods in both tasks of the bony segmentation and the landmark digitization. Our DTNet features three main technical contributions. First, a collaborative two-branch architecture is designed to efficiently capture both fine-grained image details and complete global context for high-resolution volume-to-volume prediction. Second, leveraging anatomical dependencies between landmarks, regionalized dynamic learners (RDLs) are designed in the concept of "learns to learn" to jointly regress large-scale 3D heatmaps of all landmarks under limited computational costs. Third, adaptive transformer modules (ATMs) are designed for the flexible learning of task-specific feature embedding from common feature bases.
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BACKGROUND/PURPOSE: Students with different undergraduate trainings may have different responses after taking a combined course with both clinical and basic topics. This study investigated the learning experience of basic science and clinical dentistry by postgraduate students in Institute of Clinical Dentistry (ICD) and Institute of Oral Biology (IOB) after finishing the specific course. MATERIALS AND METHODS: Semi-structure questionnaire filled by internet process was used. The data were collected and analyzed statistically. RESULTS: Nineteen participants who took the course of "panel discussion of oral oncology" since 2014 to 2018 were included in this study. Of the 19 postgraduate students, 11 were from ICD and 8 from IOB. Both ICD and IOB students gave high scores for the items such as benefit for the research, appropriateness of the discussion topics, and suitableness of problem-based teaching model. ICD students tended to have better fitness of interdisciplinary learning (Pâ¯>â¯0.05), better understanding of clinical topics (significant, Pâ¯=â¯0.02), and a higher willing to recommend other students to take the course (Pâ¯>â¯0.05) than IOB students. However, IOB students tended to have a better understanding of basic science topics than ICD students, although the difference was not significant (Pâ¯>â¯0.05). CONCLUSION: Our problem-based and constructive teaching course and the selected topics are proper and helpful for students' future research. The students with the clinical training background are prone to have better understanding of clinical topics, while those with the basic science training tend to have better understanding of basic science topics.