Tissue-engineered Maxillofacial Skeletal Defect Reconstruction by 3D Printed Beta-tricalcium phosphate Scaffold Tethered with Growth Factors and Fibrin Glue Implanted Autologous Bone Marrow-Derived Mesenchymal Stem Cells.

The study aimed to investigate whether a 3D printed beta-tricalcium phosphate (ß-TCP) scaffold tethered with growth factors and fibrin glue implanted autologous bone marrow-derived mesenchymal stem cells would provide a 3D platform for bone regeneration resulting in new bone formation with plasticity. Twenty 3D printed ß-TCP scaffolds, ten scaffolds engrained with osteogenic mesenchymal stem cells with fibrin glue (group A), and ten scaffolds used as a control group with ß-TCP scaffold and fibrin glue inoculation only (group B) were included in the study. Cell infiltration, migration, and proliferation of human osteogenic stem cells on the scaffolds were executed under both static and dynamic culture conditions. Each scaffold was examined post culture after repeated changes in the nutrient medium at 2, 4 or 8 weeks and assessed for opacity and formation of any bone-like tissues macroscopic, radiographic, and microscopic evaluation. Significant changes in all the prerequisite parameters compiled with an evaluated difference of significance showing maxillofacial skeletal repair via tissue engineering by ß-TCP scaffold and MSCs remains will be the most promising alternative to autologous bone grafts and numerous modalities involving a variety of stem cells, growth factors from platelet-rich fibrin.

Adolescent and Young Adult Oral Maxillofacial Tumors: A Single-Institution Case Series and Literature Review.

Adolescent and young adult (AYA) oral maxillofacial tumors are rare and account for ∼12% of all AYA cancers. Due to the low incidence of these malignancies, diagnostic considerations, therapeutic approaches, and factors affecting prognosis have been difficult to characterize. Given the anatomic structures located within the head and neck, patients are at risk for treatment-related morbidity that may adversely impact their quality of life. We present a single-institution case series of AYA patients with oral maxillofacial tumors treated at the University of Illinois at Chicago. A multidisciplinary treatment approach, including collaboration with the Oral Maxillofacial Surgery, Dentistry, and the Ear, Nose, and Throat teams along with the utilization of Children's Oncology Group treatment protocols, can serve as a model to address the challenges in the management of these complex cases.

Thalidomide leads to mandible hypoplasia through inhibiting angiogenesis and secondary hemorrhage in the fetal craniofacial region in rabbits.

The effect of thalidomide on mandibular development is unclear. In this study, thalidomide was delivered to pregnant rabbits from the 8th to 14th day of gestation. Then, embryos were harvested for examination on the 16th day (GD16), 20th day (GD20) and 24th day (GD24) of gestation. The results showed obvious hemorrhage and hematoma on one side of the craniofacial region in 50 % of the thalidomide-treated embryos and obvious hemorrhage and hematoma on both sides of the craniofacial region in 50 % of the thalidomide-treated embryos at GD16. Histological examination showed soft tissues and mandible defects on the affected side of the maxillofacial region. The expression of Vegf-α, Ki67 and Sox9 on the affected side was significantly down-regulated in comparison to their expression on the unaffected side at GD20. There was also an obvious defect in the affected mandible, and the density of the skull and mandible was decreased compared to the unaffected side or the control group at GD24. These findings demonstrated that thalidomide may lead to hemorrhage and hematoma in the craniofacial region by inhibiting angiogenesis, resulting in the abnormal development of cranial neural crest cells that are involved in the normal development of the mandible in rabbits.

Comparative Study of Mandible Ramus Morphology Using 3-dimensional CT in Sagittal Split Ramus Osteotomy.

The purpose of the present study was to investigate the relevance of the external morphology of the mandibular ramus, internal bone tissue structure, and maxillofacial morphology at the site for sagittal split ramus osteotomy among different facial skeletal patterns. A total of 80 patients with jaw deformities who underwent sagittal split ramus osteotomy were included in the study. The patients were divided into two groups based on facial skeletal type (skeletal Class II or skeletal Class III). A further 7 patients with no skeletal abnormalities were established as the control group (skeletal Class I). Computed tomography images obtained from these patients were 3-dimensionally reconstructed and the morphology of the mandibular ramus determined. Thickness at the mandibular foramen in Class II was greater than that in Class III, and showed the lowest value at the midpoint of the mandibular foramen and mandibular notch in Class I. Mandibular morphology showed change according to facial skeletal type. Correlations were also observed between the cephalometric analysis values and mandibular morphology.

[Diagnostic and therapeutic interest of studying the nose in maxillo-dento-facial orthopedics]. / Intérêt diagnostique et thérapeutique de l'étude du nez en orthopédie dento-maxillo-faciale.

INTRODUCTION: Orthodontists have long tried to predict future growth. It is one of the most difficult goals to achieve precisely despite the different methods of growth forecasting. A simple technique based on clinical and radiological analyses of the nose and premaxilla makes it possible, using no measurements, to accurately predict future maxillary growth and to deduce the therapeutic indications. A morphologic study of the nose is also an important item in the diagnosis of cranio-facial syndromes. MATERIALS AND METHODS: Combining detailed semiologic and radiologic studies of the nasal and premaxillary structures, this article proposes a method for evaluating and predicting facial growth. RESULTS: Experience based on many observations and current embryological knowledg can detect growth abnormalities of the ethmoïdo-nasal-premaxillary unit and provide valuable therapeutic information. DISCUSSION: Combining clinical and radiologic analyses of nasal and premaxillary morphology is a good method to predict growth of the upper face. It is also an important feature in the diagnosis of cranio-facial syndromes. CONCLUSION: This technique should be included in the diagnosis of maxillo-dento-facial orthopedic cases.

Diagnosis and Treatment of Gorham-Stout Disease in Maxillofacial Regions.

PURPOSE: This study was aimed to investigate the clinical features, imaging examination, and treatment of the patients with Gorham-Stout disease (GSD) in maxillofacial region, so as to improve the understanding of GSD. METHODS: The medical records of the patients with GSD who were referred to Shanghai Ninth People's Hospital from January 2010 to May 2016 were reviewed. Their ages, lesion location, imaging results, laboratory examination results, treatment, and therapeutic effects were analyzed. RESULTS: A total of 4 cases were included (males 2, females 2). The average onset age was 40 years. GSD attacked the mandible in 2 cases; mandible and temporal bone in 1 case; and mandible, temporal bone, and zygoma in 1 case. All cases were examined by computed tomography (CT), which showed bone resorption and atrophy of soft tissue in involved region. Four patients were given alendronate for treatment. All of them had no significant signs of progress after treatment. CONCLUSIONS: GSD can affect one single bone or multiple bones in maxillofacial region. The diagnosis mainly depends on the imaging examinations. Enhanced CT or magnetic resonance imaging is advocated for differential diagnosis of this disease. Alendronate was used with apparent good effect in these patients.

Perfil epidemiológico dos pacientes portadores de fissuras labiopalatinas atendidos por equipe cirúrgica de referência no Estado do Amazonas / Epidemiological profile of patients with orofacial cleft treated by a reference surgical team in the State of Amazonas, Brazil

Introdução: As fissuras labiopalatinas são malformações congênitas e, no Brasil, estima-se a ocorrência de 1:650 nascimentos. A classificação adotada é a de Spina. A queiloplastia e a palatoplastia são as principais cirurgias executadas. Métodos: Estudo retrospectivo descritivo com obtenção de dados a partir do sistema Smile Train Express referente a pacientes com fissura labiopalatina atendidos por equipe cirúrgica de referência entre 1 de março de 2014 e 1 de dezembro de 2016. Resultados: Foram identificados 477 pacientes, predominando o sexo masculino e os dois primeiros anos de vida na admissão. A fissura mais prevalente foi transforame e unilateral esquerda. O tratamento cirúrgico mais frequente foi a queiloplastia. Conclusões: O padrão epidemiológico está em consonância com a literatura nacional.

Introduction: Orofacial clefts are congenital malformations with an estimated occurrence of 1:650 births in Brazil. The most widely adopted classification system in that country is the method developed by Spina, and cheiloplasty and palatoplasty are the main surgeries performed. Methods: This was a retrospective descriptive study using data collected from the Smile Train Express organization regarding patients with orofacial clefts treated by a reference surgical team between March 1, 2014 and December 1, 2016. Results: A total of 477 patients were identified, predominantly male and in the first two years of life at admission. The most prevalent type of malformation was left unilateral transforamen cleft. The most frequent surgical treatment was cheiloplasty. Conclusions: The epidemiological pattern is consistent with the findings described in the national literature.

Influence of low-level laser therapy on the healing of human bone maxillofacial defects: A systematic review.

PURPOSE: This systematic review evaluates the effectiveness of low-level laser therapy (LLLT) to enhance maxillofacial area bone repair. METHODS: A comprehensive search of studies published up to February 2017 and listed in PubMed/MEDLINE, Scopus, and Cochrane Library databases was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: The 15 selected studies evaluated a total of 374 patients (mean age, 28.5years) who were treated with LLLT. Gallium-arsenide (GaAs) and gallium aluminium arsenide (GaAlAs) were the most commonly used devices, and LLLT parameters varied greatly. Wavelengths varied from 500 to 1000nm. Tooth extraction, distraction osteogenesis, maxillary expansion, periodontal defects, orthodontic movement and maxillary cystic defects were evaluated. From the 15 selected studies, six evaluated bone repair (primary outcomes). Of these, four studies showed improvement in bone formation after using LLLT, two demonstrated improved results for only one follow up period, and one showed no additional benefits. The other 9 studies evaluated secondary parameters related to healing (secondary outcomes) in the maxillofacial area after applying LLLT, including anti-inflammatory, analgesic, and healing accelerator effects, and quality of life related to oral health. There were no adverse or negative effects of LLLT reported. CONCLUSION: Within the limitation of this review, a possible improvement in bone density can be found when LLLT is applied postoperatively in maxillofacial bony defects. LLLT also seems to promote anti-inflammatory and analgesic effects and accelerate healing, as well as enhance quality of life related to oral health. However, LLLT use protocols need to be standardized before more specific conclusions can be drawn about this subject.

Clinical and molecular characterization of seven Egyptian families with autosomal recessive robinow syndrome: Identification of four novel ROR2 gene mutations.

Robinow syndrome (RS) is a rare genetic disorder characterized by limb shortening, genital hypoplasia, and craniofacial/orodental abnormalities. The syndrome follows both autosomal dominant and recessive patterns of inheritance with similar phenotypic presentation and overlapping features. Autosomal recessive Robinow syndrome (ARRS) is caused by mutations in the ROR2 gene. Here, we present the clinical, radiological and molecular findings of 11 Egyptian patients from 7 unrelated consanguineous families with clinical features of ARRS. Mutation analyses of ROR2 gene identified five pathogenic mutations distributed all over the gene. The identified mutations included four novel (G326A, D166H, S677F, and R528Q) and one previously reported (Y192D). Our results extend the number of ROR2 mutations identified so far, suggest a founder effect in the Egyptian population, and emphasize the important role of genetic testing in proper counseling and patients' management.

Characteristics of a novel treatment system for linear accelerator-based stereotactic radiosurgery.

The purpose of this study is to characterize the dosimetric properties and accuracy of a novel treatment platform (Edge radiosurgery system) for localizing and treating patients with frameless, image-guided stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT). Initial measurements of various components of the system, such as a comprehensive assessment of the dosimetric properties of the flattening filter-free (FFF) beams for both high definition (HD120) MLC and conical cone-based treatment, positioning accuracy and beam attenuation of a six degree of freedom (6DoF) couch, treatment head leakage test, and integrated end-to-end accuracy tests, have been performed. The end-to-end test of the system was performed by CT imaging a phantom and registering hidden targets on the treatment couch to determine the localization accuracy of the optical surface monitoring system (OSMS), cone-beam CT (CBCT), and MV imaging systems, as well as the radiation isocenter targeting accuracy. The deviations between the percent depth-dose curves acquired on the new linac-based system (Edge), and the previously published machine with FFF beams (TrueBeam) beyond D(max) were within 1.0% for both energies. The maximum deviation of output factors between the Edge and TrueBeam was 1.6%. The optimized dosimetric leaf gap values, which were fitted using Eclipse dose calculations and measurements based on representative spine radiosurgery plans, were 0.700 mm and 1.000 mm, respectively. For the conical cones, 6X FFF has sharper penumbra ranging from 1.2-1.8 mm (80%-20%) and 1.9-3.8 mm (90%-10%) relative to 10X FFF, which has 1.2-2.2mm and 2.3-5.1mm, respectively. The relative attenuation measurements of the couch for PA, PA (rails-in), oblique, oblique (rails-out), oblique (rails-in) were: -2.0%, -2.5%, -15.6%, -2.5%, -5.0% for 6X FFF and -1.4%, -1.5%, -12.2%, -2.5%, -5.0% for 10X FFF, respectively, with a slight decrease in attenuation versus field size. The systematic deviation between the OSMS and CBCT was -0.4 ± 0.2 mm, 0.1± 0.3mm, and 0.0 ± 0.1 mm in the vertical, longitudinal, and lateral directions. The mean values and standard deviations of the average deviation and maximum deviation of the daily Winston-Lutz tests over three months are 0.20 ± 0.03 mm and 0.66 ± 0.18 mm, respectively. Initial testing of this novel system demonstrates the technology to be highly accurate and suitable for frameless, linac-based SRS and SBRT treatment.

[Upper eyelid congenital coloboma, aethiology pathogenesis and management]. / Colobome congénital de la paupière supérieure, étiologie physiopathologie et prise en charge.

Coloboma of the upper eyelid is a rare congenital disease. It is defined as an agenesis of the eyelid free edge. Multiple patho-physiological theories exist about its etiology. The surgical therapeutic management of this malformation is clearly codified. We illustrate the presentation by two cases treated in the Groupement Hospitalier Nord of Lyon University Hospital.

Partial trisomy of the pericentromeric region of chromosome 5 in a girl with binder phenotype.

The patient reported here displayed most characteristic features of Binder syndrome (OMIM: 155050), a rare maxillonasal malformation with unknown etiology. She was sent for genetic evaluation at the age of 10 years because of facial dysmorphism and borderline intellectual disability. Cytogenetic analyses showed a de novo supernumerary small ring chromosome with a pericentromeric region of chromosome 5 in all lymphocytes. Array painting revealed that the marker contains a 20,950-kb genomic region comprising cytogenetic band 5p14.1q11.1. Additionally, 7 reports have been published in the literature with partial trisomy of chromosome 5 overlapping with our case. These 8 cases were analyzed for phenotype/genotype correlation which suggested that the maxillonasal anomalies of Binder phenotype and trisomy of the pericentromeric region of chromosome 5 may be in causal relationship. Future functional annotation studies of genes localized in this genomic region should take this into consideration. To the best of our knowledge, this is the first report on a patient with association of a chromosome abnormality and clinical characteristics of Binder phenotype.

Guilty as CHARGED: p53's expanding role in disease.

Unrestrained p53 activity during development, as occurs upon loss of the p53 negative regulators Mdm2 or Mdmx, causes early embryonic lethality. Surprisingly, co-expression of wild-type p53 and a transcriptionally-dead variant of p53, with mutations in both transactivation domains (p53(L25Q,W26S,F53Q,F54S)), also causes lethality, but later in gestation and in association with a host of very specific phenotypes reminiscent of a syndrome known as CHARGE. Molecular analyses revealed that wild-type p53 is inappropriately activated in p53(5,26,53,54/)(+) embryos, triggering cell-cycle arrest or apoptosis during development to cause CHARGE phenotypes. In addition, CHARGE syndrome is typically caused by mutations in the CHD7 chromatin remodeler, and we have shown that activated p53 contributes to phenotypes caused by CHD7-deficiency. Together, these studies provide new insight into CHARGE syndrome and expand our understanding of the role of p53 in diseases other than cancer.

CHARGE syndrome: an overview on dental and maxillofacial features.

OBJECTIVES: CHARGE is an acronym referring to the aspects of this rare syndromic condition. Patients with CHARGE association are today considered as subjects lacking in pathognomonic dental alterations. The present study is aimed at adding to the body of evidence of the cases reported in literature and the continuous clinical research which show a clinical picture which is strongly associated with patients afflicted by this syndrome. PATIENTS AND METHODS: We report a case-series of 8 patients with CHARGE syndrome. The dental features associated with CHARGE syndrome are from case-reports, but without a congruity that can lead to a definition of the dental condition typical of the CHARGE phenotype. CONCLUSIONS: The systemic problems affecting these patients are predominant in compromising their quality of life: this is the reason for a frequent lack of a diagnostics and interceptive phase, relative to oral diseases. We report new oral pathological conditions affecting CHARGE patients. Knowledge of these pathological conditions may induce dentists to carry out specific diagnoses of these patients, thus, avoiding the deterioration of oral conditions.

Engineering anatomically shaped vascularized bone grafts with hASCs and 3D-printed PCL scaffolds.

The treatment of large craniomaxillofacial bone defects is clinically challenging due to the limited availability of transplantable autologous bone grafts and the complex geometry of the bones. The ability to regenerate new bone tissues that faithfully replicate the anatomy would revolutionize treatment options. Advances in the field of bone tissue engineering over the past few decades offer promising new treatment alternatives using biocompatible scaffold materials and autologous cells. This approach combined with recent advances in three-dimensional (3D) printing technologies may soon allow the generation of large, bioartificial bone grafts with custom, patient-specific architecture. In this study, we use a custom-built 3D printer to develop anatomically shaped polycaprolactone (PCL) scaffolds with varying internal porosities. These scaffolds are assessed for their ability to support induction of human adipose-derived stem cells (hASCs) to form vasculature and bone, two essential components of functional bone tissue. The development of functional tissues is assessed in vitro and in vivo. Finally, we demonstrate the ability to print large mandibular and maxillary bone scaffolds that replicate fine details extracted from patient's computed tomography scans. The findings of this study illustrate the capabilities and potential of 3D printed scaffolds to be used for engineering autologous, anatomically shaped, vascularized bone grafts.

Interaction between Foxc1 and Fgf8 during mammalian jaw patterning and in the pathogenesis of syngnathia.

Syngnathia (bony fusion of the upper and lower jaw) is a rare human congenital condition, with fewer than sixty cases reported in the literature. Syngnathia typically presents as part of a complex syndrome comprising widespread oral and maxillofacial anomalies, but it can also occur in isolation. Most cartilage, bone, and connective tissue of the head and face is derived from neural crest cells. Hence, congenital craniofacial anomalies are often attributed to defects in neural crest cell formation, survival, migration, or differentiation. The etiology and pathogenesis of syngnathia however remains unknown. Here, we report that Foxc1 null embryos display bony syngnathia together with defects in maxillary and mandibular structures, and agenesis of the temporomandibular joint (TMJ). In the absence of Foxc1, neural crest cell derived osteogenic patterning is affected, as osteoblasts develop ectopically in the maxillary prominence and fuse with the dentary bone. Furthermore, we observed that the craniofacial musculature is also perturbed in Foxc1 null mice, which highlights the complex tissue interactions required for proper jaw development. We present evidence that Foxc1 and Fgf8 genetically interact and that Fgf8 dosage is associated with variation in the syngnathic phenotype. Together our data demonstrates that Foxc1 - Fgf8 signaling regulates mammalian jaw patterning and provides a mechanistic basis for the pathogenesis of syngnathia. Furthermore, our work provides a framework for understanding jaw patterning and the etiology of other congenital craniofacial anomalies, including temporomandibular joint agenesis.

Segmental curvilinear distraction osteogenesis.

Curvilinear distraction is currently under investigation to reconstruct curved maxillofacial bone defects. However, previous studies have revealed the discrepancy between the contour of the regenerated bone in the distraction gap and the curvilinear pathway of the transport disc. We hypothesize that the discrepancy is because of the conflict of the distraction vector and the strain vector during the consolidation. In curvilinear distraction osteogenesis, the distraction vector varies, while the strain vector during the consolidation phase is fixed-linear, from the beginning to the end of the distraction pathway. Here we bring forward a solution of segmental curvilinear distraction osteogenesis to divide the curvilinear distraction into several segments, with respective consolidation for each distraction gap. If this hypothesis is verified, the segmental distraction curvilinear distraction will benefit the reconstruction of complicated long-range maxillofacial bone defects.