Cranial Vault Bones Research Articles

Acalvaria, rare congenital malformation in palestine: case report and literature review

Introduction and Importance: Acalvaria is a rare congenital anomaly characterized by absent cranial vault bones, often misdiagnosed as anencephaly or encephalocele. Case Presentation: We present a case of a 10-day-old male neonate with Acalvaria, delivered normally at 37+5 weeks, with a birth weight of 2.7 kg and dysmorphic features including low-set ears and a sandal gap. Skull X-ray revealed absent parietal, temporal, and frontal bones. Initially admitted for potential sepsis, he has since shown normal development at three months, with ongoing conservative management. Clinical Discussion: Acalvaria is a rare congenital malformation marked by the absence of cranial vault bones, dura mater, and scalp muscles. Our case presents partial calvaria absence with normal skull base, classified as primary acalvaria. Associated anomalies necessitate thorough evaluation for prognosis. Diagnosis can occur as early as 12 weeks gestation via ultrasound, but management remains conservative, focusing on supportive care and monitoring for potential surgical interventions later. Conclusion: Acalvaria is a rare, fatal anomaly requiring conservative management; antenatal care and psychological preparation are essential for affected families.

Brain microbleeds resulting from presumed extensive fat emboli in a patient with bone marrow necrosis following a sickle cell disease vaso-occlusive crisis.

Acute manifestations of sickle cell disease (SCD) are numerous and multisystemic.Cerebral fat embolism (CFE) is a rare but serious complication of SCD caused by bone marrow necrosis (BMN) during vaso-occlusive crises (VOC). We present the case of a41-year-old man with SCD who developed severe VOC and multi-organ dysfunction.He subsequently experienced neurological deterioration with decreased consciousness and diffuse encephalopathy on serial electroencephalograms. Bone marrow aspiration confirmed BMN. Brain MRI revealed extensive diffuse leukoencephalopathy, vasogenic and cytotoxic edema in the white matter, patchy edema in the cranial vault bone marrow on fat-suppressed FLAIR sequence (a finding consistent with the confirmed BMN), and multiple cerebral microbleeds on susceptibility-weighted imaging consistent with CFE. The management of acute neurological complications of SCD varies depending on the specific complication. Brain MRI plays a crucial role in the accurate diagnosis of these complications to guide appropriate treatment.

Fraser syndrome with limb reduction defect: a rare and unique anatomic variation.

Fraser syndrome, named after George Fraser, is an autosomal recessive disorder showing a highly variable interfamilial phenotypic variation, with malformations ranging from minor symptoms to lethal anomalies like renal agenesis, incompatible with survival. Limb reduction defects have not been reported to be associated with it. A 21-year-old primigravida presented to the antenatal outpatient department with a level two targeted anomaly scan report suggestive of severe oligohydramnios with suspected renal agenesis. The cranial vault bones were compressed, and orbital globes and lenses could not be visualized. Renal agenesis was confirmed due to sleeping adrenals sign, non-visualization of the urinary bladder, and Doppler of renal arteries. A detailed examination of the fetal head in the sagittal section showed the absence of an eye globe and lens, arousing suspicion of Fraser syndrome. After pregnancy termination, a complete fetal autopsy was done to look for any additional findings. Patients who have a syndromic mix of acrofacial and urogenital abnormalities with or without cryptophthalmos should be evaluated for Fraser syndrome, which can be diagnosed by clinical examination and perinatal autopsy.

Joint multi-ancestry and admixed GWAS reveals the complex genetics behind human cranial vault shape

The cranial vault in humans is highly variable, clinically relevant, and heritable, yet its genetic architecture remains poorly understood. Here, we conduct a joint multi-ancestry and admixed multivariate genome-wide association study on 3D cranial vault shape extracted from magnetic resonance images of 6772 children from the ABCD study cohort yielding 30 genome-wide significant loci. Follow-up analyses indicate that these loci overlap with genomic risk loci for sagittal craniosynostosis, show elevated activity cranial neural crest cells, are enriched for processes related to skeletal development, and are shared with the face and brain. We present supporting evidence of regional localization for several of the identified genes based on expression patterns in the cranial vault bones of E15.5 mice. Overall, our study provides a comprehensive overview of the genetics underlying normal-range cranial vault shape and its relevance for understanding modern human craniofacial diversity and the etiology of congenital malformations.

Skull and scalp ultrasound in children: a review

INTRODUCTION: An important task of modern pediatrics is to ensure radiation safety of diagnostic examinations, especially in young children. One of the options for reducing radiation exposure at the stages of screening diagnostics and dynamic monitoring is a wider use of ultrasound.OBJECTIVE: To analyze the data of domestic and foreign literature on the possibilities of ultrasound examination of the cranial vault bones, cranial sutures and scalp in children.MATERIALS AND METHODS: The literature search was performed in open Russian and English databases Medline, PubMed, Web of Science, RSCI, eLIBRARY using keywords and phrases: «skull ultrasound», «scalp ultrasound», «cranial sutures ultrasound», «point of care ultrasound», «pediatric POCUS» without limitation of retrospective depth.RESULTS: Based on the literature data and our own long-term experience in the use of cranial ultrasonography in clinical practice, the indications and examination technique, as well as the key ultrasound signs of the most frequent types of pathology are described. Prospects of scalp and skull ultrasonography within PoCUS, FAST, including the use of portable sonoscopes based on smartphones and tablets are outlined.CONCLUSION: Ultrasound of the skull and scalp is a quick, simple, affordable, harmless method of screening and monitoring the most frequent types of pathologies of the cranial vault bones, cranial sutures, and soft tissues of the scalp in children (for example, fractures, synostoses, neoplasms).

Infigratinib, a selective FGFR1-3 tyrosine kinase inhibitor, alters dentoalveolar development at high doses.

Fibroblast growth factor receptor-3 (FGFR3) gain-of-function mutations are linked to achondroplasia. Infigratinib, a FGFR1-3 tyrosine kinase inhibitor, improves skeletal growth in an achondroplasia mouse model. FGFs and their receptors have critical roles in developing teeth, yet effects of infigratinib on tooth development have not been assessed. Dentoalveolar and craniofacial phenotype of Wistar rats dosed with low (0.1 mg/kg) and high (1.0 mg/kg) dose infigratinib were evaluated using micro-computed tomography, histology, and immunohistochemistry. Mandibular third molars were reduced in size and exhibited aberrant crown and root morphology in 100% of female rats and 80% of male rats at high doses. FGFR3 and FGF18 immunolocalization and extracellular matrix protein expression were unaffected, but cathepsin K (CTSK) was altered by infigratinib. Cranial vault bones exhibited alterations in dimension, volume, and density that were more pronounced in females. In both sexes, interfrontal sutures were significantly more patent with high dose vs vehicle. High dose infigratinib administered to rats during early stages affects dental and craniofacial development. Changes in CTSK from infigratinib in female rats suggest FGFR roles in bone homeostasis. While dental and craniofacial disruptions are not expected at therapeutic doses, our findings confirm the importance of dental monitoring in clinical studies.

CURRENT INFORMATION ON THE DEVELOPMENT AND FORMATION OF THE STRUCTURE OF SMALL BONES OF THE FACIAL DIVISION OF THE SKULL

The development of the cranial vault bone system is ensured by the sequential development and displacement of various rudiments, which merge, spread and take an indirect part in the formation of the face. The analysis of modern scientifi c literature allows us to come to the conclusion that, despite a number of scientifi c works in human anatomy, the morphogenesis of small bones of the facial skull remains an actual direction of modern medicine. As you know, the small bones of the facial skull include the lacrimal, nasal, zygomatic, palatine bones, the lower nasal concha, which are paired, and the unpaired – the scapula and hyoid bone. Primary ossifi cation of the lacrimal bone appears in the third month of fetal development. Among the anomalies of the nasal conchas, pneumatization, agenesis, and their doubling are quite often detected. The ossifi cation of the ploughshare develops from two connective tissue plates, which fuse together in the process of ossifi cation (beginning in the third month of embryogenesis). Ossifi cation of the nasal bone is determined from one point of ossifi cation, which appears in the third month of embryogenesis. The zygomatic bone undergoes the connective tissue and bone stages of development, the ossifi cation of the nucleus appears in the 8th week of intrauterine development. For a long time, the hyoid bone has been the object of anatomical discussions regarding the peculiarities of its embryonic origin, variants of its structure, position and function. Conclusion. On the basis of the conducted research, it can be stated that in the scientifi c literature there are isolated data on the development and formation of the small bones structure in the perinatal period of ontogenesis of the facial skull. Currently there are no comprehensive studies on the density of bone tissue, morphometric characteristics and correlative relationships of the small bones of the facial skull with the parameters of the face and skull as a whole during the fetal and early neonatal periods of ontogenesis. Last is the basis for determining the morphological prerequisites for the appearance of variants of the facial structure and its congenital defects and determine the need for further anatomical study.

The Role of Connexin‐43 in Cranial Neural Crest Cell Differentiation

BackgroundMost features of the craniofacial complex that are necessary for feeding derive from cranial neural crest cells (cNCCs). These pluripotent stem cells originate from the dorsal neural folds and undergo a series of coordinated processes such as induction, epithelial‐to‐mesenchymal transition (EMT), migration, and differentiation. While most of these processes have been well‐studied for their roles in development, much remains to be known about the final step cNCCs must undergo, differentiation. Connexin‐43 (Cx43) is a gap junctional protein that is widely expressed, evolutionarily conserved, and has been well‐studied for its impacts on neural crest and bone. Previous research has shown that loss of Cx43 function impacts neural crest EMT and migration and can delay early osteoblast and chondrocyte differentiation; however, it is unknown how Cx43 deficiency in cNCCs impacts cNCC differentiation into osteochondrogenic lineages and the resultant impacts on craniofacial morphology. Therefore, the purpose of this project is to determine the effects of a neural crest‐specific loss of Cx43 on osteogenic and chondrogenic differentiation, and how these effects may alter skull phenotype.MethodsWe have developed a mouse model wherein the gene encoding for Cx43 has been conditionally knocked out in neural crest cells and their derivatives using the Wnt1‐Cre2 driver (Wnt1‐Cre2+/‐;mTmG+/+;Cx43fl/fl, herein Cx43cKO). To compare the developing skull phenotype between Cx43cKO mice and littermates in which the Cx43 gene is not floxed (Wnt1‐Cre2+/‐; mTmG+/+, herein Cx43WT), we will collect homologous landmark data from microCT images of newborn skulls and use geometric morphometric analyses to quantify and visualize shape differences in neural crest‐ and mesoderm‐derived portions of the skull between genotypes.To determine the localized effects of a neural‐crest specific loss of Cx43 function on osteoblast and chondrocyte differentiation, we will use immunofluorescence staining. Expression of chondrocyte, osteoblast, and osteocyte differentiation markers will be localized and semi‐quantitatively compared between genotypes and between neural crest‐ and mesoderm‐derived cells. With these assays, we aim to understand the relationship between Cx43, cNCC differentiation, and the subsequent impacts on skull morphology.Preliminary ResultsCx43cKO neonates show decreased ossification compared to Cx43WT littermates, which is most prominent in facial bones such as the nasal bones, and cranial vault bones such as the frontal and parietal bones. Potential driving forces for this decreased ossification in neural crest‐ and mesoderm‐derived bones are delayed differentiation of the osteoblast‐osteocyte lineage and disrupted signaling between cells in neighbouring bones.Significance & Future DirectionsThis study will help elucidate the role of cNCC differentiation in skull development, and how loss of Cx43 function impacts skull development. We will add embryonic and post‐natal timepoints to further understand the impacts of neural crest‐specific deletion of Cx43 throughout development; pilot data with Cx43cKO adult mice show that alterations to skull shape persist and overtly affect the face and mandible.

Head, chest and limbs mine-explosive wounds

The article presents the experience of treating wounded K., 29 years old, who, as a result of the suicide bombing of a homemade shell-free explosive device in a moving car of the St. Petersburg Metro 03.04.2017 received a severe mine-explosive combined wound to the head, chest and limbs with a fragmented blind skull. The trauma was accompanied by brain damage, a fracture of the cranial vault bones, lungs contusion, and fragmented fracture of the right tibia bones. The patient underwent sequential bifrontal decompressive craniotomy, external fixation of the right shin bones fractures, blocked intramedullary osteosynthesis of the latter, dura mater plasty, cranioplasty with a titanium plate after its computer modeling. The complex treatment allowed the patient to be discharged from the hospital after 4 months in a satisfactory condition.

Differentiation of osteoblast lineage cells that form dermal bones and sutures of the anterior cranial vault in development and disease

FGFR-related craniosynostosis syndromes, such as Apert syndrome, are characterized in part by dysmorphology of the anterior cranial vault bones and early closure of the coronal suture. Understanding the cellular processes during early formation of the anterior cranial vault bones and the coronal suture is key to the development of therapies for these syndromes. Runt-related transcription factor 2 (RUNX2) and Osterix (OSX) play critical roles in the regulation of osteoblast differentiation and function and are first expressed at different stages of osteoblast lineage cell (OLC) development. RUNX2 is known to act upstream of OSX and is expressed during an earlier stage of OLC differentiation, but relatively little is known about the behavior and developmental sequence of OLCs that contribute to the initial formation of cranial dermal bones and the sutures between them. To address this issue, we made the R2Tom transgenic mouse line by introducing the tdTomato reporter gene joined with an enhancer fragment of the human RUNX2 gene and the Hsp68 minimal promoter sequence that labels developmentally early OLCs. Crossing this novel R2Tom mouse line with the Osx-GFP line produced R2Tom;Osx-GFP mice, in which expression of RUNX2 and Osx is detected with different fluorescent reporters. The R2Tom;Osx-GFP mouse line was then crossed with Fgfr2+/P253R;Emx1-Cre (referred to below as Apert) mice that show phenotypes similar to Apert syndrome patients to produce Apert;R2Tom;Osx-GFP mice and “unaffected” littermates that carry the fluorescent marker but do not express the mutant Fgfr2 gene. Using large field, high-resolution fluorescent microscopy (ranging between 12.5x and 112x) and light sheet microscopy, we captured expression of RUNX2 and Osx across the surface of whole mouse embryos and at the cellular level. R2Tom;Osx-GFP and Apert;R2Tom;Osx-GFP mice were developmentally staged to provide precise information about the developmental sequence of expression of RUNX2 and Osx and 3D physical organization of early OLCs during the cellular assembly of what will be the frontal and parietal bones and initiation of the coronal suture in mouse embryos between E11.5 to E14.5. Our preliminary data on Apert;R2Tom;Osx-GFP mice at E12.5 and E13.5 reveal differences in the timing and pattern of the developmental sequence of RUNX2 and Osx expression in the anterior cranial vault of mice carrying the Fgfr2+/P253R mutation relative to their unaffected litter mates. These results provide our first view of OLC differentiation in the anterior cranial vault of Fgfr2+/P253R Apert mice prior to the formation of anterior cranial vault bones and the coronal suture and suggest that differences in the timing of OLC patterning play an import role in dysmorphologies of the anterior cranial vault.

Morphometric Study of Cranial Bones in Japanese Quail Embryo; Coturnix japonica

Morphometric study of cranial bones had not studied well in avian; hence Japanese quail embryos were an important model in the developmental research because it had a short incubation period. In the current study, seventy fertilized eggs of Japanese quail collected, forty-two embryos used for anatomical study, and twenty-eight embryos used for histological study. The anatomical study demonstrated cranial bones consisted of two parts cranial base and cranial vault. On 3rd to 9th day of incubation, the cranial base chondrified to numbers of cartilage templates. On 10th to 13th day of incubation, these cartilages ossified and replaced by bones. In contrast cranial vault bones ossified directly from 8th to 10th day of incubation. Histological study displayed on 3rd to 9th day of incubation, cranial base chondrified through condensation and differentiation of mesenchymal cells areas to cartilage templates. On 10th to 12th day of incubation, bone collar formed. On 12th to 14th day of incubation, endochondral ossification centers of all cranial base bones occurred. On 14th to 16th day of incubation, woven bones created. While, cranial vault bones developed through condensation and differentiation of mesenchymal cells to osteoblasts directly, and intramembranous ossification centers of all cranial vault bones formed from 8th to 10th day of incubation. On 12th to 16th day of incubation, woven bones created. The current study summarized chondrification and ossification of cranial bones of Japanese quail embryos.

G9a is involved in the regulation of cranial bone formation through activation of Runx2 function during development.

The methyltransferase G9a was originally isolated as a histone methyltransferase that catalyzes the methylation of histone 3 lysine 9 (H3K9) to a dimethylated state (H3K9me2). Recent studies have revealed that G9a has multiple functions in various cells, including osteoblasts. Here, we investigated G9a function during cranial bone formation. Crossing Sox9-cre with G9aflox/flox (fl/fl) mice generated conditional knockout mice lacking G9a expression in Sox9-positive neural crest-derived bone cells. Sox9-Cre/G9afl/fl mice showed severe hypo-mineralization of cranial vault bones, including defects in nasal, frontal, and parietal bones with opened fontanelles. Cell proliferation was inhibited in G9a-deleted calvarial bone tissues. Expression levels of bone marker genes, i.e., alkaline phosphatase and osteocalcin, were suppressed, whereas Runx2 expression was not significantly decreased in those tissues. In vitro experiments using G9a-deleted calvarial osteoblasts showed decreased cell proliferation after G9a deletion. In G9a-deleted osteoblasts, expression levels of fibroblast growth factor receptors and several cyclins were suppressed. Moreover, the expression of bone marker genes was decreased, whereas Runx2 expression was not altered by G9a deletion in vitro. G9a enhanced the transcriptional activity of Runx2, whereas siRNA targeting G9a inhibited the transcriptional activity of Runx2 in C3H10T1/2 mesenchymal cells. We confirmed the direct association of endogenous Runx2 with G9a. Chromatin immunoprecipitation experiments showed that G9a bound to Runx2-target regions in promoters in primary osteoblasts. Furthermore, Runx2 binding to the osteocalcin promoter was abrogated in G9-deleted osteoblasts. These results suggest that G9a regulates proliferation and differentiation of cranial bone cells through binding to and activating Runx2.

Опыт применения аддитивных технологий для реконструктивных операций в челюстно-лицевой хирургии

Introduction. Modern technologies make it possible not only to plan reconstructive surgery virtually, but also to manufacture templates for resection and osteotomy, customized titanium plates based on the results of planning.
 Objective. To analyze the results of application of additive technologies for planning and performing reconstructive operations in the Maxillofacial Surgery and Stomatology Center at Burdenko Main Military Clinical Hospital 
 Patients and Methods. 144 operations to eliminate different locations bone defects were performed in the Maxillofacial Surgery and Stomatology Center in 2007 - 2017. 136 patients (93%) had de-fects of the bones of the facial skeleton and the skull calvarium. In other cases, there were defects of the clavicle (2 patients), defects of the femur (2 patients), defects of the humerus (2 patients), a defect of the radius (1 patient), a defect of the navicular bone (1 patient).
 Results. Flaps were used to close the defects in 87% of cases (125 patients), and alloplastic implants were utilized in 13% of cases (19 patients). Additive technologies were used in 85% (n = 123) cases for planning the operation to eliminate defects, as well as for manufacturing surgical models and templates. Clinical cases are considered as examples of the use of the additive technologies for planning and performing reconstructive operations to close bone defects of different locations.
 The incidence of postoperative complications in the group of patients with facial skeleton and crani-al vault bones defects who underwent surgical interventions using templates was 26%, including minor complications - 17.5%, large - 8.5%. Among minor complications, hematomas (5%) and sup-puration (5%) of the recipient wound prevailed, less often similar complications were hematomas (4%) and suppuration (3%) of the donor wound. Large complications were represented by cases of complete (4%) or partial (5%) transplant necrosis.
 During surgical interventions without a template, it took significantly longer than the average time of grafting and graft formation (212 ± 18.7 min) than during operations with a template, including with a guide for drilling (136 ± 12.6 min, p <0.001) and without a guide for drilling (160 ± 16.3 min, p <0.001).
 Conclusion. The use of surgical models and templates during reconstructive operations shortens the time of the operation and reduces the number of postoperative complications.

Modern materials for the reconstruction of the cranial vault bones

Introduction. The need for cranioplasty occurs after the removal of the bony structures of the cranial vault. Craniotomy can be performed both in emergency as in case of increased intracranial pressure, and as a planned operation in the treatment of neoplasms or abscesses. A long-lasting presence of an extensive bone defect is the cause of the "trephined skull" syndrome development. Currently, cranioplasty is performed with materials of synthetic or natural origin. Synthetic materials include hydroxyapatite, tricalcium phosphate, polymethyl methacrylate. The natural materials include the auto-, allo- and xenografts. The main disadvantage of bone autografts is their rapid lysis. The most promising solution to this problem may include a lyophilization method with transplant saturation with growth factors, the source of which can be autoplasma rich in platelets. Of particular relevance is the development of methods for the preparation and preservation of an autograft, its modification in order to increase osteoreparative properties, which will bring the cranioplasty method with natural transplants to a whole new level.The purpose of research. Combine relevant data and the results of a comprehensive analysis of the advantages and disadvantages of existing bone-plastic materials.

Autophagy Regulates Craniofacial Bone Acquisition.

Increasing evidence has demonstrated the important role of autophagy in skeletal homeostasis; however, the role of autophagy in craniofacial bone development and acquisition is largely unknown. In this study, we investigated the effect of autophagy suppression on craniofacial bone acquisition by deleting Fip200 or Atg5, two essential autophagy genes, using Osterix-Cre (Osx-Cre). We found that the Osx-Cre transgene mildly decreased the bone mass of parietal bone but not frontal bone, and did not affect cranial base bone mass in adult mice. In the cranial vault, Fip200 or Atg5 deletion similarly decreased 50% bone mass of neural crest-derived frontal bone; Atg5 deletion decreased 50% and Fip200 deletion decreased 30% bone mass of mesoderm-derived parietal bone. In the cranial base, Fip200 or Atg5 deletion similarly decreased 30% bone mass of neural crest-derived presphenoid bone; Atg5 deletion decreased 30% and Fip200 deletion decreased 16% bone mass of mesoderm-derive basioccipital bone. Lastly, we used doxycycline treatment to inhibit the Osx-Cre expression until 2months of age and showed that postnatal Fip200 deletion led to cranial vault bone mass decrease in association with a small increase in both bone volume/tissue volume and tissue mineral density. Altogether, this study demonstrated the important role of autophagy in craniofacial bone acquisition during development and postnatal growth.

Possibilities of single photon emission tomography in the diagnosis of bone metastases in patients with disseminated medullary thyroid carcinoma (case report)

The study objective : using a clinical example to demonstrate possibilities of single photon emission computerized tomography (SPECT) in combination with computed tomography (CT) in identifying latent bone metastases, taking into account the dynamics growth of serum basal calcitonin. Materials and methods . Patient S., 60 years old, visited N.N. Blokhin National Medical Research Center of Oncology for consultation on multiple lung metastases of cancer of unknown primary. Results. Taking into account basal calcitonin level, immunohistochemistry, ultrasound investigation andfine-needle aspiration biopsy of the node in the right thyroid lobe a diagnose of medullary thyroid cancer was made. CT revealed multiple metastases in both lungs. Specialist erformed thyroidectomy with central lymphadenectomy and facial neck dissection on both sides. During next four months basal calcitonin level increased twice. Control contrast CT lung screening showed the growth of previously identified metastases and the appearance of multiple new ones. Bone scan showed focuses of increased radio-pharmaceutical accumulation in the area of 7 h left rib, left iliac wing, in the left bones of cranial vault, in C 7 , Th 6 , Th 9 , Th I2 vertebrae and right foot bones. Additional examination using SPECT/CT (from the skull base to the hip joints) revealed metastases in corpuses of Th 9 , Th I2 vertebrae and the left iliac wing, and suspicion for metastasis in 7 h left rib. Magnetic resonance imaging (MRI) confirmed metastasis in Th 9 , Th I2 , L 3 vertebral bodies and in the left iliac wing. Conclusion. Conclusion . In this clinical example, SPECT/CT allowed to correctly detect metastases in both Th 9 and Th I2 vertebrae while bone scan was questionable, and MRI showed an additional damage of L 3 vertebra. Changes in the 7 h left rib could not be verified using CT, although this changes may be an emerging metastasis. Obviously, extensive use of radiation methods does not guarantee complete identification of all pathological focuses, it therefore allows assessing the prevalence of the pathological process. It is crucially important to control calcitonin level in these patients, since its rapid growth allowed suspecting additional distant metastases.

A coupled reaction-diffusion-strain model predicts cranial vault formation in development and disease.

How cells utilize instructions provided by genes and integrate mechanical forces generated by tissue growth to produce morphology is a fundamental question of biology. Dermal bones of the vertebrate cranial vault are formed through the direct differentiation of mesenchymal cells on the neural surface into osteoblasts through intramembranous ossification. Here we join a self-organizing Turing mechanism, computational biomechanics, and experimental data to produce a 3D representative model of the growing cerebral surface, cranial vault bones, and sutures. We show how changes in single parameters regulating signaling during osteoblast differentiation and bone formation may explain cranial vault shape variation in craniofacial disorders. A key result is that toggling a parameter in our model results in closure of a cranial vault suture, an event that occurred during evolution of the cranial vault and that occurs in craniofacial disorders. Our approach provides an initial and important step toward integrating biomechanics into the genotype phenotype map to explain the production of variation in head morphology by developmental mechanisms.

Exploring Mechanisms of Cranial Vault Development using a Coupled Turing‐Biomechanical Model

Bones of the mouse cranial vault are formed by differentiation of mesenchymal cells into osteoblasts, a process called intramembranous ossification that is primarily thought to be controlled by a cascade of reactions between extracellular molecules and cells that may be significantly guided by mechanical forces. In this study, we use a computational approach and an extensive experimental database to elucidate the role of biomechanics in morphogenesis of the cranial vault. We assume that the biochemical process can be modeled using Turing's reaction-diffusion model, a mathematical model describing the pattern formation controlled by interacting molecules (activators and inhibitors). In addition, we hypothesize that mechanical stimuli of the cells due to growth of the underlying brain contributes significantly to the process of cell differentiation. We have developed a coupled framework that incorporates these modeling constructs. The mathematical formulation was solved using the finite volume method. The computational domain and model parameters are determined using a large collection of experimental data that provides precise three-dimensional measures of mouse cranial geometry and cranial vault bone formation for specific embryonic time points. The results of this study suggest that mechanical strain contributes information to specific aspects of bone formation. Our mechanobiological model predicts some key features of cranial vault bone formation that were verified by experimental observations in normal case, including the relative location of ossification centers of the individual vault bones, the pattern of cranial vault bone growth over time, and the position of cranial vault sutures. Support or Funding Information Computations for this research were performed on the Pennsylvania State University's Institute for Cyber Science Advanced Cyber Infrastructure (ICS-ACI). This work was supported in part through instrumentation funded by a National Science Foundation grant OCI0821527, a Burroughs-Wellcome Fund 2013 Collaborative Research Travel Grant, Pennsylvania Department of Health using Tobacco Cure Funds, and by the National Institutes of Health grants R01DE022988 and P01HD078233. The model predicts the pattern of cranial vault bone growth. a) Computational prediction of the distribution of differentiating osteoblasts and cranial vault bone formation by embryonic day. b) Observed cranial vault bone formation and growth in embryonic mice. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Experience with resorbable sonic pins for the attachment of distraction devices in posterior cranial vault distraction operations

BackgroundDistraction techniques are effective methods for the treatment of craniosynostoses when a significant gain of an intracranial volume is required. However, this technique raises some challenges at different stages of the treatment. While installing the distractors in patients with thin calvarial bone, there is a risk of dural damage from the titanium screws. The need for wide exposure of the devices and the screws during removal causes soft tissue damage and bleeding.ObjectiveThis study aimed to evaluate sonic pin use in the distraction procedures.MethodsResorbable sonic pins were used in 11 consecutive posterior cranial vault distraction procedures to attach distraction devices to the calvarial bone.ResultsThis method allowed for a less traumatic and faster removal of the devices without the risk of leaving foreign bodies in the wound. In three out of 11 cases on follow-up, displacement of proximal distractor footplate and partial relapse of distraction were detected. Though there was a smaller volume increase in these patients, all of them benefited clinically from the PCVD and did not require reoperations.ConclusionsThis method allows a strong and stable attachment of the distractor devices to the cranial vault bones with a reduced risk of dural tears due to the screws. It also allows for easier and less traumatic device removal.

Некоторые морфологические особенности регенерации костей свода черепа при использовании костнопластических биоматериалов (предварительные данные)

Некоторые морфологические особенности регенерации костей свода черепа при использовании костнопластических биоматериалов (предварительные данные)