Vault Sutures Research Articles

The biomechanics of chewing and suckling in the infant: A potential mechanism for physiologic metopic suture closure.

Craniosynostosis is a condition with neurologic and aesthetic sequelae requiring invasive surgery. Understanding its pathobiology requires familiarity with the processes underlying physiologic suture closure. Animal studies have shown that cyclical strain from chewing and suckling influences the closure of cranial vault sutures, especially the metopic, an important locus of craniosynostosis. However, there are no human data correlating strain patterns during chewing and suckling with the physiologically early closure pattern of the metopic suture. Furthermore, differences in craniofacial morphology make it challenging to directly extrapolate animal findings to humans. Eight finite-element analysis (FEA) models were built from craniofacial computer tomography (CT) scans at varying stages of metopic suture closure, including two with isolated non-syndromic metopic craniosynostosis. Muscle forces acting on the cranium during chewing and suckling were simulated using subject-specific jaw muscle cross-sectional areas. Chewing and suckling induced tension at the metopic and sagittal sutures, and compressed the coronal, lambdoid, and squamous sutures. Relative to other cranial vault sutures, the metopic suture experienced larger magnitudes of axial strain across the suture and a lower magnitude of shear strain. Strain across the metopic suture decreased during suture closure, but other sutures were unaffected. Strain patterns along the metopic suture mirrored the anterior to posterior sequence of closure: strain magnitudes were highest at the glabella and decreased posteriorly, with minima at the nasion and the anterior fontanelle. In models of physiologic suture closure, increased degree of metopic suture closure correlated with higher maximum principal strains across the frontal bone and mid-face, a strain regime not observed in models of severe metopic craniosynostosis. In summary, our work provides human evidence that bone strain patterns from chewing and suckling correlate with the physiologically early closure pattern of the metopic suture, and that deviations from physiologic strain regimes may contribute to clinically observed craniofacial dysmorphism.

Time course of sutural width during the physiological growth from birth to adulthood: CT quantitative and qualitative evaluations of sutural arches.

We performed a retrospective qualitative and quantitative evaluation of the sutural changes during the physiological growth to define the age-related ossification stages of major and minor skull sutures or synchondroses. A total of 390 healthy subjects, examined for cranio-facial trauma and whose CT scans turned out to be normal, were clustered into homogenous age-matched groups ranged from birth to 90years. High-resolution CT was used to assess the degree of sutural closure according to a 3-grade scoring system, the sutural pattern, the width, and the density of the gap calculated as the average of two or three ROIs along each suture/synchondrosis. The identification of a definite pattern depended on the suture's type, the closure degree, and the width of the gap (p < 0.001). The interdigitation process was more intricate for most of vault sutures than the skull base sutures/synchondroses. Closing grades 1, 2, and 3 were associated to an identifiable sutural pattern and the cutoff value of 1.45mm of the gap width allowed to detect an identifiable sutural pattern with the best combination of sensitivity (97%) and specificity (98%). Age and sutural closing degree were inversely related to gap width while positively related to the gap density (p < 0.001). The sutural ossification is an age-related process, distinctive for each suture, and synchondrosis; it occurs neither according to a predefined order along sutural arches nor following a sequential distribution in the cranial fossae, and some sutures continued their growth process during lifetime.

Machine learning-based identification of craniosynostosis in newborns

Early closure of cranial vault sutures, defined as craniosynostosis is a relatively common condition with somehow specific head and face abnormality for each subtype. Early diagnosis results in a better prognosis but pediatricians and primary care providers are not so familiar with these abnormalities while taking 3D CT scan of skull, predisposes the growing brain to harmful effects of radiation. Thus, developing a user-friendly and accurate diagnostic system would be helpful. This study aimed to diagnose simple suture synostosis by using machine learning based methods in digital photographs of child head. Digital photos of 145 craniosynostosis infants, operated in Mofid children hospital (Tehran, Iran) are used in this study. Head border is identified by GrabCut algorithm segmentation method and then several anthropometric indices such as cranial index (CI), cranial vault asymmetry index (CVAI), anterior–midline width ratio (AMWR) and anterior–posterior​ width ratio (APWR) and left–right height ratio (LRHR) are calculated. Moreover, statistical pattern matching indices (Chi-square (CS), Hu moment invariants (HuMI), absolute difference of white pixels probability (AbsDifWPP) and pixel intensity (PI)) are calculated and compared to anthropometric indices. The classification results for statistical pattern matching indices varied in the range of 85%–92% which is statistically higher than hand crafted indices. Our proposed approach could diagnose and classify common subtypes of single suture craniosynostosis and could help pediatricians and parents in early diagnosis and follow-up of this disorder.

A study of 285 cases of cranial vault suture closure in Chinese adults.

To examine the presence and characteristics of cranial vault suture closure in Chinese adults and to explore whether craniosacral therapy (CST) manipulation is rational from the anatomical perspective. Anthropological non-metric observation and craniometry were used to study 285 dry skull specimens of Chinese adults. A total of 91 specimens with closed extracranial sutures were observed, with an occurrence rate of 31.93%. Based on the mode of closure, there were 32 cases of single type closure, with sagittal suture closure predominating with 20 cases (21.98%); 59 cases of composite closure, with a partial closure of coronal suture + sagittal suture + lambdoid suture predominating with 26 cases (28.57%). In terms of the degree of closure, there were 13 cases (14.28%) of sagittal suture grade 0 closure and 78 cases (85.72%) of grade 1 - 4 closure; 34 cases (37.36%) of coronal suture grade 0 closure and 57 cases (62.64%) of grade 1 - 4 closure; 47 cases (51.65%) of lambdoid suture grade 0 closure and 44 cases (48.35%) of grade 1 - 4 closure. The segment and degree of coronal suture closure (46, 80.7%) and lambdoid suture (31, 70.45%) were mostly left-right symmetrical. The bone surfaces on either side of the cranial vault sutures are embedded in each other, forming a rough, complex and interlocking bone-suture-bone structure. This study observed the closure of the cranial vault suture, summarized its characteristics, and explored the irrationality of the CST manipulation. The anatomical characteristics of the cranial suture dictate that manipulation cannot push the cranial suture at will.

Age determination from closure of skull vault sutures during autopsy

Age determination from closure of skull vault sutures during autopsy

Analysis of Cranial Base Suture Fusion Patterns.

It is known from both anatomic and radiographic studies that the majority of cranial sutures begin fusing in early adulthood and are fused by late adulthood. However, most of the studies focus on the cranial vault rather than the cranial base. Most clinicians treating patients with craniosynostosis are interpreting the behavior of cranial sutures on CT imaging. Therefore, the purpose of this study was to further clarify the radiographic appearance of cranial base sutures over the natural human life span. Thirty CT scans of the head and face were reviewed for each decade starting at 1 year of life up to age 90. Scans were evaluated for the appearance of the occipitomastoid, petrosoocciptial, sphenosquamous, sphenopetrosal, frontosphenoidal, sphenozygomatic, petrososquamosal, frontoethmoidal, sphenoethmoidal and sphenoccipital sutures. Sutures were categorized as obliterated, present with fusion, present without fusion and unable to visualize. The majority of cranial base sutures are visible up through the eighth decade, although evidence of ossification across the suture starts as early as the second decade. Some sutures such as the occipitomastoid appeared > 90% open even as late as the ninth decade. Other sutures such as the sphenosquamosal and frontozygomatic are mostly fused by that age. Cranial base sutures appear to behave radiographically similar, to the cranial vault sutures in that they largely remain visible throughout adulthood but show varying amounts of ossification. There are some cranial base sutures which appear to remain open throughout life although the significance of this has yet to be determined.

GLI1 and AXIN2 Are Distinctive Markers of Human Calvarial Mesenchymal Stromal Cells in Nonsyndromic Craniosynostosis.

All skeletal bones house osteogenic stem cell niches, in which mesenchymal stromal cells (MSC) provide progenitors for tissue growth and regeneration. They have been widely studied in long bones formed through endochondral ossification. Limited information is available on the composition of the osteogenic niche in flat bones (i.e., skull vault bones) that develop through direct membranous ossification. Craniosynostosis (CS) is a congenital craniofacial defect due to the excessive and premature ossification of skull vault sutures. This study aimed at analysing the expression of GLI1, AXIN2 and THY1 in the context of the human skull vault, using nonsyndromic forms of CS (NCS) as a model to test their functional implication in the aberrant osteogenic process. The expression of selected markers was studied in NCS patients’ calvarial bone specimens, to assess the in vivo location of cells, and in MSC isolated thereof. The marker expression profile was analysed during in vitro osteogenic differentiation to validate the functional implication. Our results show that GLI1 and AXIN2 are expressed in periosteal and endosteal locations within the osteogenic niche of human calvarial bones. Their expression is higher in MSC isolated from calvarial bones than in those isolated from long bones and tends to decrease upon osteogenic commitment and differentiation. In particular, AXIN2 expression was lower in cells isolated from prematurely fused sutures than in those derived from patent sutures of NCS patients. This suggests that AXIN2 could reasonably represent a marker for the stem cell population that undergoes depletion during the premature ossification process occurring in CS.

What Is the Skull Structure Influence of Squamosal Suture Synostosis in Nonsyndromic and Syndromic Crouzon Craniosynostosis?

The morphologic effect of squamosal synostosis has not been clarified, due to its low occurrence rate, and its inclination to be combined with premature closure of other major sutures, especially in syndromic synostosis. This study's goal is to explore the morphological influence of squamosal synostosis in both syndromic and nonsyndromic craniosynostosis patients. Twenty-five computed tomography (CT) scans from nonsyndromic squamosal synostosis (NSS), Crouzon syndrome with squamosal synostosis (CSS), Crouzon syndrome without squamosal synostosis, and normal controls were included. Three-dimensional (3D) cephalometry, entire cranial volume and cranial fossa volume were measured using Materialise software. The entire cranial volume of all groups was similar. The NSS developed a gradual reduction in the severity of reduced segmental volume from the anterior cranial fossa, to the middle cranial fossa, and to the unaffected volume of posterior cranial fossa. The CSS developed the most severe volume reduction of middle cranial fossa (12608.30 ± 2408.61 mm vs 26077.96 ± 4465.74 mm, 52%), with proportionate volume reduction of the anterior (7312.21 ± 2435.97 mm vs 10520.63 ± 2400.43 mm, 30%) and posterior cranial fossa (33487.29 ± 5598.93 mm vs 48325.04 ± 14700.44 mm, 31%). The NSS developed a narrower anterior cranial fossa, a clockwise rotated Frankfort horizontal plane, and a retracted chin (pogonion). Squamosal synostosis may alter the development of cranial fossa volume, especially the volume of middle cranial fossa. However, the development of cranial base, and related facial features are determined largely by major vault sutures and associated syndromic conditions, rather than the squamosal suture alone. II.

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.

Study of sagittal suture closure at autopsy: A three-year prospective study

The skeleton is a principle source of information in age estimation. It is difficult to estimate age after 25 years. Changes in the pubic symphysis, transparency of root and root length measurement have been considered as good parameters to estimate age beyond 25 years. The reliability of skull suture closure alone in age estimation still remains doubtful. Sagittal suture is considered to be the most accurate among the other vault sutures. Hence this study was conducted to check for its reliability in age estimation. It was observed that, sagittal suture closure starts earlier on the endocranial surface than on the ectocranial surface. Ectocranially females showed earlier fusion than males, but endocranial suture closure was earlier in males. Ectocranial fusion started between 20–29 years, with maximum closure occurringby 60 years. Endocranialfusion alsostartedbetween20-29 years and achieved maximum closure by55years.

Determination of age from fusion of skull vault sutures

Background: Cranial suture closure has long been recognized as a character of human development related to aging. For this reason, it has been utilized for various forensic and archaeological studies to determine the age of an unidentified/or skeletonized individuals. Various cadaveric studies have established the role of lambdoid suture in age estimation, but not routinely practiced. Age estimation is an integral part of the biological profile employed by forensic anthropologists in order to assist in achieving an identification of an unknown deceased individual. The main objective of this article is to determine the pattern of cranial vault suture closure in relation to age. Material and methods: Total number of 90 subjects, 25 years and beyond were included in the study, and divided into four groups with an age interval of 10 years. Each individual was subjected to radiological examination of the skull with a view to• study the Sagittal, Coronal and Lambdoid sutures, a special view was evolved by trial in order to get all the basic three sutures in one film. Ectocranial and endocranial closure pattern were studied. Result: A significant difference was observed between the age group and suture closure. Coronal suture was the first to fuse followed by sagittal suture. Lambdoid suture. Endocranially, starts fusing at the age of 25‐30 yrs. Closure was found earlier in females compared to males. Conclusion: Suture obliteration occurs earlier on endocranial surface. Based on endocranial suture fusion, Coronal suture was first to close followed by sagittal suture, lambdoid suture sequentially.

A Cross Sectional Postmortem Study on Closure of Skull Vault Sutures with Respect to Age from 3Rd to 6Th Decades of Life

A Cross Sectional Postmortem Study on Closure of Skull Vault Sutures with Respect to Age from 3^Rd to 6^Th Decades of Life

Skull morphometry and vault sutures of Myrmecophaga tridactyla and Tamandua tetradactyla

ABSTRACT This study aimed to examine the relationship between skull size and the level of cranial vault suture closure. A total of 50 Myrmecophaga tridactyla Linnaeus, 1758 and 178 Tamandua tetradactyla Linnaeus, 1758 skulls were analyzed in relation to 18 skull dimensions. The skulls were grouped into three levels of suture closure: no sutures closed (level 0), one or all the fallowing sutures closed: interfrontalis, sagitalis and coronalis (level 1) and all sutures closed (level 2). The results indicated that among the 18 variables measured, 17 showed significant differences (p ≤ 0.01) between level 0 and level 1 skulls of T. tetradactyla; as well as between level 0 and level 1, and level 0 and level 2 skulls of M. tridactyla. M. tridactyla level 1 and level 2 had no significant difference among any of the 18 dimensions. The foramen magnum height in both species showed no significant difference (p &gt; 0.05) among any suture categories. In principle, suture closure level and cranial dimensions are related. The specimens with larger cranial dimensions showed greater number of cranial vault sutures closed for both species of anteaters. Tamandua tetradactyla and M. tridactyla specimens with none of the cranial vault suture closed have a foramen magnum height similar to those with cranial vault suture closed.

Overexpression of Glypican 3 Promotes Proliferation, Regulates Cell Cycle Progression, and Inhibits Apoptosis of Human Fetal Osteoblastic Cell Line 1.19.

Craniosynostosis is a complex disease condition, which involves premature fusion of cranial vault sutures and lacks desirable treatment. Previous studies have demonstrated decreased proliferation rate of osteoblasts and downregulated expression of glypican 3 (GPC3) in syndromic craniosynostosis patients. In this study, quantitative and qualitative analysis were utilized to assess the effect of GPC3 in human fetal osteoblastic cell line, hFOB 1.19. Lentiviral transfection efficiency with green fluorescent protein images was obtained after 72 hours. Western Blot and quantitative real-time polymerase chain reaction analysis results indicated that GPC3 was overexpressed in hFOB 1.19 cells transfected with recombinant lentivirus LV-GPC3-GFP. Cell proliferation was assessed by CCK-8 assay and cell cycle progression and apoptosis were analyzed by flow cytometric assay. Results revealed that GPC3 promoted cell viability, induced cell cycle entry into S phase, and inhibited cell apoptosis. These findings provide novel ideas in understanding the pathogenesis of craniosynostosis. It also provides novel insights in the treatment of craniosynostosis by targeting GPC3.

A COMPUTATIONAL ANALYSIS OF BONE FORMATION IN THE CRANIAL VAULT USING A COUPLED REACTION-DIFFUSION-STRAIN MODEL.

Bones of the murine cranial vault are formed by differentiation of mesenchymal cells into osteoblasts, a process that is primarily understood to be controlled by a cascade of reactions between extracellular molecules and cells. We assume that the process can be modeled using Turing's reaction-diffusion equations, a mathematical model describing the pattern formation controlled by two interacting molecules (activator and inhibitor). In addition to the processes modeled by reaction-diffusion equations, we hypothesize that mechanical stimuli of the cells due to growth of the underlying brain contribute significantly to the process of cell differentiation in cranial vault development. Structural analysis of the surface of the brain was conducted to explore the effects of the mechanical strain on bone formation. We propose a mechanobiological model for the formation of cranial vault bones by coupling the reaction-diffusion model with structural mechanics. 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 provide precise three dimensional (3D) measures of murine 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 including the relative location of ossification centers of individual vault bones, the pattern of cranial vault bone growth over time, and the position of cranial vault sutures.

Age Assessment from Vault Sutures Closure in Elderly Persons: An Autopsy Study in Haroti Region

In India, even after frequent stress paid on Birth & death registration, most of the people are not following it and hence the age verification is a great problem, especially among the illiterates.

The Significance of Squamosal Suture Synostosis.

The squamosal suture is one of the lateral minor skull sutures, separating the parietal and squamous temporal bones. While the phenotypic appearances and sequelae of synostosis of the major cranial vault sutures are well documented, little is reported concerning synostosis of the squamosal suture (SQS). The aim of this study was to determine the frequency of squamosal suture synostosis, and to document the significance of this entity.A retrospective review of the diagnostic imaging for all new pediatric patients (aged ≤16 years) referred to the Oxford Craniofacial Unit between January 2008 and February 2013 was completed to identify patients with SQS. Computed tomography (CT) imaging was available in 422 patients and the axial and three-dimensional reconstructed images reviewed.Squamosal suture synostosis was confirmed in 38 patients (9%). It was present in conjunction with major suture synostosis in 33 patients and in isolation in 5. The incidence increased with age. It was more common in patients with syndromic craniosynostosis (18%) and associated syndromic conditions (36%) than in those with isolated major suture synostosis (6%). It was found to occur with coronal, lambdoid, and sagittal synostosis, but was most frequent with multisuture fusion patterns. Squamosal suture synostosis was not associated with a consistent calvarial deformity either in isolation or when associated with a major suture fusion. No patient underwent surgery specifically to correct SQS.In conclusion, contrary to previous reports, squamosal suture synostosis is a relatively frequent finding in the general case mix of a typical craniofacial unit, but is of limited clinical significance.

Craniosynostosis: current conceptions and misconceptions

AbstractCranial bones articulate in areas called sutures that must remain patent until skull growth is complete. Craniosynostosis is the condition that results from premature closure of one or more of the cranial vault sutures, generating facial deformities and more importantly, skull growth restrictions with the ability to severely affect brain growth. Typically, craniosynostosis can be expressed as an isolated event, or as part of syndromic phenotypes. Multiple signaling mechanisms interact during developmental stages to ensure proper and timely suture fusion. Clinical outcome is often a product of craniosynostosis subtypes, number of affected sutures and timing of premature suture fusion. The present work aimed to review the different aspects involved in the establishment of craniosynostosis, providing a close view of the cellular, molecular and genetic background of these malformations.

FGFR2c-mediated ERK–MAPK activity regulates coronal suture development

Fibroblast growth factor receptor 2 (FGFR2) signaling is critical for proper craniofacial development. A gain-of-function mutation in the 2c splice variant of the receptor's gene is associated with Crouzon syndrome, which is characterized by craniosynostosis, the premature fusion of one or more of the cranial vault sutures, leading to craniofacial maldevelopment. Insight into the molecular mechanism of craniosynostosis has identified the ERK–MAPK signaling cascade as a critical regulator of suture patency. The aim of this study is to investigate the role of FGFR2c-induced ERK–MAPK activation in the regulation of coronal suture development. Loss-of-function and gain-of-function Fgfr2c mutant mice have overlapping phenotypes, including coronal synostosis and craniofacial dysmorphia. In vivo analysis of coronal sutures in loss-of-function and gain-of-function models demonstrated fundamentally different pathogenesis underlying coronal suture synostosis. Calvarial osteoblasts from gain-of-function mice demonstrated enhanced osteoblastic function and maturation with concomitant increase in ERK–MAPK activation. In vitro inhibition with the ERK protein inhibitor U0126 mitigated ERK protein activation levels with a concomitant reduction in alkaline phosphatase activity. This study identifies FGFR2c-mediated ERK–MAPK signaling as a key mediator of craniofacial growth and coronal suture development. Furthermore, our results solve the apparent paradox between loss-of-function and gain-of-function FGFR2c mutants with respect to coronal suture synostosis.

Understanding craniosynostosis as a growth disorder.

Craniosynostosis is a condition of complex etiology that always involves the premature fusion of one or multiple cranial sutures and includes various anomalies of the soft and hard tissues of the head. Steady progress in the field has resulted in identifying gene mutations that recurrently cause craniosynostosis. There are now scores of mutations on many genes causally related to craniosynostosis syndromes, though the genetic basis for the majority of nonsyndromic cases is unknown. Identification of these genetic mutations has allowed significant progress in understanding the intrinsic properties of cranial sutures, including mechanisms responsible for normal suture patency and for pathogenesis of premature suture closure. An understanding of morphogenesis of cranial vault sutures is critical to understanding the pathophysiology of craniosynostosis conditions, but the field is now poised to recognize the repeated changes in additional skeletal and soft tissues of the head that typically accompany premature suture closure. We review the research that has brought an understanding of premature suture closure within our reach. We then enumerate the less well-studied, but equally challenging, nonsutural phenotypes of craniosynostosis conditions that are well characterized in available mouse models. We consider craniosynostosis as a complex growth disorder of multiple tissues of the developing head, whose growth is also targeted by identified mutations in ways that are poorly understood. Knowledge gained from studies of humans and mouse models for these conditions underscores the diverse, associated developmental anomalies of the head that contribute to the complex phenotypes of craniosynostosis conditions presenting novel challenges for future research. WIREs Dev Biol 2016, 5:429-459. doi: 10.1002/wdev.227 For further resources related to this article, please visit the WIREs website.