Craniofacial Form Research Articles

Supernumerary Sutures in the Zygoma and their Impacts on Skull Modularity and Biomechanics

Craniofacial sutures are weak points compared to rigid bone on the skull and hence must be shielded from unduly high stresses so as not to disrupt vital growth processes and skeletal functions, especially in areas such as the midface. Under rare circumstances, extra sutures may naturally present in the midface, an area of critical morphological and biomechanical importance, such as intrazygomatic sutures dividing the zygoma into multiple parts (incidence of up to 6.5% in modern human populations, 0.24% in rhesus macaques, and 4.4% in orangutans). However, how these extra sutures would impact the ontogeny and function of facial skeletons has not been systematically studied. In this study, using 3D images and a Finite Element Model simulating the condition of the divided zygoma, the morphological and biomechanical influences of the supernumerary sutures in the midface were investigated. In skulls with unilateral divided zygoma, the bone was transected by the supernumerary intrazygomatic suture that arises perpendicularly from the facial aspect of the maxillo‐zygomatic suture and runs dorsolaterally, separating the zygoma into a superior division and an inferior division (bipartite). When compared to the normal side, the superior division was slender with the weaker muscle/fascia attachment markings on the frontal process, while the inferior division was more robust, with a thicker temporal process. The bones on the affected side that articulated with the inferior division also demonstrated signs of bony strengthening, including a thicker zygomatic process of the temporal bone contributing to a more robust zygomatic arch, and thickening of the lateroinferior part of the zygomatic process of the maxillary bone. Biomechanical simulations revealed that the superior division was spared high stress flow in the normal condition at the expense of the inferior division. In this way, the stresses incurred during normal masticatory activities were shunted from the upper face to the lower face, especially along the zygomatic arch, which is heavily stressed during normal conditions, suggesting that the bipartite morphology is less optimal than the typical case. These findings revealed that the divided zygoma condition would alter overall morphology of the midface of the affected side, and unfavorably affect the pattern of stress distribution in the loaded side of the face during mastication. This suggests that the presence of supernumerary sutures disturbs the integrity and modularity of zygomatic development leading to consequent morphological and functional adaptations. Further insights into this rare condition may deepen our understanding of craniofacial form, adaptation, and evolution, and help to improve therapeutic philosophies in corrective and regenerative medicine.

Differential Scaling Patterns in Maxillary Sinus Volume and Nasal Cavity Breadth Among Modern Humans.

Among modern humans, nasal cavity size and shape reflect its vital role in air conditioning processes. The ability for the nasal cavity to augment its shape, particularly in inferior breadth, likely relates to the surrounding maxillary sinuses acting as zones of accommodation. However, much is still unknown regarding how nasal and sinus morphology relate to each other and to overall craniofacial form, particularly across diverse populations with varying respiratory demands. As such, this study uses computed tomographic (CT) scans of modern human crania (N = 171) from nine different localities to investigate ecogeographic differences in (1) the interaction between maxillary sinus volume (MSV) and nasal cavity breadth (NCB) and (2) scaling patterns of MSV and NCB in relation to craniofacial size. Reduced major axis (RMA) regression reveals that all samples exhibit an inverse relationship between MSV and NCB, but statistical significance and the strength of that relationship is sample dependent. Individuals from cold-dry climates have larger MSVs with narrower NCBs, while smaller MSVs are associated with wider NCBs in hot-humid climates. MSV and NCB each scale with positive allometry relative to overall craniofacial size. However, sample differences are evident in the both the interaction between MSV and NCB, as well as their correlation with craniofacial size. While these results provide further support that the maxillary sinus and nasal cavity are integrated among populations from opposite ends of the climatic spectrum, additional epigenetic factors are needed to explain variation of these structures among populations from more intermediate climates.

A new operative open-wings technique to correct the frontoforehead unit in metopic synostosis.

The technology adoption and creation of a multidisciplinary team have helped to overcome the complexity associated. Craniofacial surgery has thus emerged from the valuable contributions of neurosurgery, maxillofacial surgery, plastic surgery, eyes, nose, and throat as well as head and neck surgery. A patient with trigonocephaly may present a prominent "keel" forehead, accompanied by recession of the lateral orbit rims, hypotelorism, and constriction of the anterior frontal fossa when the metopic suture fuses before 6 months of age. In a period between 2007 and 2011, in the Salesi Children's Hospital, were treated for nonsyndromic variety of metopic synostosis 11 infants; their ages ranged from 6 months to 9 months, and 7 were males and 4 females. The most important aims of our new surgical technique are the achievement of symmetry as well as normal proportion and reconstruction of the frontoforehead unit but remaining in a very conservative treatment. The morphology and position of the supraorbital ridge-lateral orbital rim region are key elements of upper facial esthetics. This new "open-wings" technique for the reconfiguration of the bilateral emisupraorbital bar requires a midline incomplete osteotomy that involves only the internal cortex of the frontonasal region. Hence, both lateral orbital walls are bent inwardly and tilting forward, as in computed tomographic scan planning, with a greenstick fracture pivoting on the preserved medial frontonasal region. This open-wings conservative technique allows the avoidance of the most important complication that may result in the traditional way such as dead space in the anterior cranial fossa, infections, and blood loss but with an achievement of satisfactory craniofacial form and aesthetic result.

The effects of tissue-non-specific alkaline phosphatase gene therapy on craniosynostosis and craniofacial morphology in the FGFR2C342Y/+ mouse model of Crouzon craniosynostosis.

Craniosynostosis, the premature fusion of cranial bones, has traditionally been described as a disease of increased bone mineralization. However, multiple mouse models of craniosynostosis display craniosynostosis simultaneously with diminished cranial bone volume and/or density. We propose an alternative hypothesis that craniosynostosis results from abnormal tissue mineralization through the downregulation of tissue-non-specific alkaline phosphatase (TNAP) enzyme downstream of activating mutations in FGFRs. Neonatal Crouzon (FGFRC342Y/+) and wild-type (FGFR+/+) mice were injected with lentivirus to deliver a recombinant form of TNAP. Mice were sacrificed at 4 weeks postnatal. Serum was collected to test for alkaline phosphatase (AP), phosphorus, and calcium levels. Craniofacial bone fusion and morphology were assessed by micro-computed tomography. Injection with the TNAP lentivirus significantly increased serum AP levels (increased serum AP levels are indicative of efficient transduction and production of the recombinant protein), but results were variable and dependent upon viral lot and the litter of mice injected. Morphological analysis revealed craniofacial form differences for inferior surface (p=0.023) and cranial height (p=0.014) regions between TNAP lentivirus-injected and vehicle-injected Crouzon mice. With each unit increase in AP level, the odds of lambdoid suture fusion decreased by 84.2% and these results came close to statistical significance (p=0.068). These results suggest that TNAP deficiency may mediate FGFR2-associated craniosynostosis. Future studies should incorporate injection of recombinant TNAP protein, to avoid potential side effects and variable efficacy of lentiviral gene delivery.

Facial development and alterations in FGF signaling in a mouse model of Crouzon Syndrome

Mutations in FgfR2 cause several craniosynostosis syndromes, including Crouzon Syndrome (CS), but knowledge of the specific mechanisms by which FGF effects morphogenesis is lacking. The gene CRISPLD2 is associated with non-syndromic cleft lip/palate. Preliminary data indicate it is a novel intracellular target of FGF signaling and alters facial morphology and fibroblast migration rates in vitro. Using a FgfR2W290R mouse model of CS, we investigated the development of the CS facial phenotype and how FGFR2 activity and CRISPLD2 dosage affect cell responses to extracellular FGF. Embryos at stages E9.5-E13.5 were genotyped, photographed, sectioned, and/or used for mouse embryonic fibroblast (MEF) cell lines. Facial shape was quantified using 2-D geometric morphometrics. Cell proliferation and apoptosis in facial primordia were assayed. MEF responses to extracellular FGF were assessed using pMEK expression and cell migration vectors. MEFs were infected with a CRISPLD2 virus (or control) and tests were repeated. At E10.5 (N=104), homozygous mutants (-/-) were rarer than expected, suggesting early embryonic lethality, and had significantly narrower faces and asymmetrical maxillary processes. This is surprising given the wider faces observed in CS patients and previously demonstrated in a chick embryo model. Facial shapes in +/- and +/+ embryos did not differ significantly after accounting for allometry from E9.5-E13.5. Preliminary results show increased apoptosis in the maxillary and mandibular processes of -/- embryos. We are currently analyzing cell proliferation results and performing in vitro analyses. This work will provide insight on how upstream and downstream modulators of FGF signaling regulate craniofacial form.

Craniosynostosis: The Potential Contribution of Thyroid-Related Mechanisms

Craniosynostosis, the premature fusion of one or more cranial sutures, leads to abnormal craniofacial form and function. Its causes remain largely unknown. One of the strongest clues regarding non-syndromic craniosynostosis etiology is its association with thyroid-related disorders, which is based on a mix of epidemiologic and experimental findings. This paper reviews evidence for the contribution of thyroid-related mechanisms to craniosynostosis and makes recommendations for how to improve this knowledge.

Craniofacial form is altered by chronic adult exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in Han/Wistar and Long–Evans rats with different aryl hydrocarbon receptor (AhR) structures

Mammalian bone has shown a variety of responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure in experimental and wildlife studies. Although many responses have been well characterized in the postcranial skeleton, dioxin-induced effects on the cranium are largely unknown. In this study, we investigated the effects of chronic adult exposure to TCDD on cranial size and shape in dioxin-resistant Han/Wistar (H/W) and dioxin-sensitive Long–Evans (L–E) rat strains. Three-dimensional landmark configurations for the face, vault, and base of the cranium were recorded and analyzed using geometric morphometrics (GM) and dose–response modeling. The strongest effects were shown by L–E and H/W rats with daily exposures of 100 and 1000ng TCDD/kg bw/day, respectively, resulting in significant reductions in centroid size (CS) in all three cranial modules for both strains except for the vault in H/W rats. Consistent with previous evidence of intraspecific variation in TCDD resistance, the benchmark doses (CEDs) for cranial size reduction in L–E rats were roughly 10-fold lower than those for H/W rats. For both strains, the face showed the greatest size reduction from the highest doses of TCDD (i.e., 3.6 and 6.3% decreases in H/W and L–E rats, respectively), most likely related to dose-dependent reductions in limb bone size and body weight gain. However, intrinsic morphological differences between strains were also observed: although the control groups of H/W and L–E rats had vaults and bases of comparable size, the face was 6.4% larger in L–E rats. Thus, although H/W rats possess an altered aryl hydrocarbon receptor (AhR) that appears to mediate and provides some resistance to TCDD exposure, their smaller reductions in facial size may also relate to strain-specific patterns of cranial development and growth. Future research will be aimed at understanding how ontogenetic factors may modulate toxic effects of prenatal and lactational exposure on the mammalian skeleton.

Wnt signalling underlies the evolution of new phenotypes and craniofacial variability in Lake Malawi cichlids

Progress towards understanding adaptive radiations at the mechanistic level is still limited with regard to the proximate molecular factors that both promote and constrain evolution. Here we focus on the craniofacial skeleton and show that expanded Wnt/β-catenin signalling early in ontogeny is associated with the evolution of phenotypic novelty and ecological opportunity in Lake Malawi cichlids. We demonstrate that the mode of action of this molecular change is to effectively lock into place an early larval phenotype, likely through accelerated rates of bone deposition. However, we demonstrate further that this change toward phenotypic novelty may in turn constrain evolutionary potential through the corresponding reduction in craniofacial plasticity at later stages of ontogeny. In all, our data implicate the Wnt pathway as an important mediator of craniofacial form and offer new insights into how developmental systems can evolve to both promote and constrain evolutionary change.

Morphometry and fabric orientation of trabecular bone in human craniofacial regions (918.17)

Variation in primate craniofacial form has been attributed to orofacial function. Strain gage experiments show that during orofacial function the zygoma is subjected to high strain relative to the browridge. Trabecular bone morphometry and orientation are reflective of function, but trabecular bone in these regions has been unexplored. This study uses µCT to quantify the morphometric properties of trabecular bone, anisotropy, and fabric orientation in the human browridge and zygoma. We hypothesize that zygomatic trabecular bone will have significantly greater bone volume fraction and anisotropy relative to the browridge as an adaption to larger, more unidirectional loads. Primary orientations of trabecular bone will differ by region consistent with their function.No significant differences were found between the browridge and zygoma in BVF (0.38 vs. 0.31), and DA (1.65 vs. 1.85), but SMI was significantly lower in the browridge (0.075; honeycomb‐like vs. SMI=1.0752; ideal plate‐like, p<0.034). Orientation was highly significantly different between regions. The zygoma is made up of mediolaterally oriented plates with a slight inferosuperior tilt, while trabecular bone in the browridge is made of denser sagittally oriented plates.Both regions may be more similar in overall elasticity than predicted, but further analysis needs to test the combined effects of differences in individual features. Orientation of trabeculae in the zygoma appears to be consistent with what would be predicted based on orofacial strain patterns.Grant Funding Source: NSF BCS 0725141

Neural Crest Development and Craniofacial Morphogenesis Is Coordinated by Nitric Oxide and Histone Acetylation

Cranial neural crest (CNC) cells are patterned and coalesce to facial prominences that undergo convergence and extension to generate the craniofacial form. We applied a chemical genetics approach to identify pathways that regulate craniofacial development during embryogenesis. Treatment with the nitric oxide synthase inhibitor 1-(2-[trifluoromethyl] phenyl) imidazole (TRIM) abrogated first pharyngeal arch structures and induced ectopic ceratobranchial formation. TRIM promoted a progenitor CNC fate and inhibited chondrogenic differentiation, which were mediated through impaired nitric oxide (NO) production without appreciable effect on global protein S-nitrosylation. Instead, TRIM perturbed hox gene patterning and caused histone hypoacetylation. Rescue of TRIM phenotype was achieved with overexpression of histone acetyltransferase kat6a, inhibition of histone deacetylase, and complementary NO. These studies demonstrate that NO signaling and histone acetylation are coordinated mechanisms that regulate CNC patterning, differentiation, and convergence during craniofacial morphogenesis.

A case of isolated craniofacial fibrous dysplasia – Radiologist's perspective

Fibrous dysplasia is a disease characterized by replacement of bone by fibro osseous tissue. FD has four different disease patterns. They are monostotic, polyostotic and McCune–Albright syndrome. Craniofacial pattern of disease occurs in 10–25% of patients with monostotic form and in 50% with polyostotic form. It also occurs as isolated craniofacial form. In isolated variety no extracranial lesions are present. Radiographic diagnosis plays an important role in diagnosis, classification and assessing prognosis of fibrous dysplasia. In this paper we report a case of isolated craniofacial type of fibrous dysplasia in a young female patient involving the maxilla and skull bones with a complete radiographic CT assessment of the extent of the lesion. Temporal bone involvement and bilateral lesion in certain cranial bones are the rare findings noted in this case.

A new operative “open-wind” technique to correct the fronto-forehead unit in the metopic synostosis

Patient with trigonocephaly may present a prominent “keel”, forehead accompanied by recession of the lateral orbit rims, hipotelorism and constriction of the anterior frontal fossa. In a period between 2007 and 2011, in the “Child Salesi Hospital”, were treated for nonsyndromic variety of metopic synostosis eleven children; the age of ranges from 6 months to 9 months. The most important aims of our new surgical technique is the achievement of symmetry and normal proportion and reconstruction of the fronto-forehead unit but remaining in a very conservative treatment. The morphology and position of supraorbital ridge-lateral orbital rim region are key elements of upper facial aesthetics. This new “open-wind” technique for the reconfiguration of the bilateral supraorbital bar requires a medial incomplete osteotomy that involve only the internal cortex of the fronto-nasal region. So both lateral orbital walls are bent inwardly and tilting forward, as CT scan planning, with a greenstick fracture pivoting on the preserved medial fronto-nasal region. This “open-wind” conservative technique allow to avoid the most important complication that may result with traditional way such as dead space in the anterior cranial fossa, infections, blood loss but with an achievement of satisfactory craniofacial form.

Radiation-induced craniofacial deformities: A new classification and management algorithm

Little is written about the spectrum of late radiation-induced craniofacial abnormalities and the guidelines for treating these abnormalities. The clinical records of 13 patients (eight males and five females) who received childhood craniofacial radiation between birth and 11 years of age and who subsequently had reconstructive surgery were reviewed. Eleven patients had their irradiation at the age from 1 to 5 years. The other two patients received their treatment at a relatively older age (9 and 11 years). Their deformities ranged from isolated soft-tissue deficiency with no or minimal bony deficiency to cases having osseous deformities with or without soft-tissue deficiency but still the normal or near-normal craniofacial form can be obtained with surgical intervention and the outermost extreme of the deformity is the patients whose normal or near-normal craniofacial form and function cannot be regained even with much sophisticated surgeries. Our new classification is based on two factors: the tissue component of the deformity and the possibility of regaining a normal or near-normal craniofacial form and function with the planned surgical intervention. Based on this classification, a new treatment algorithm was created.

Incidence of Intrazygomatic Sutures in Rhesus Macaques

Craniofacial sutures are weak points compared to rigid bone on the skull thence they must be shielded from unduly high stresses so as not to disrupt vital growth processes and skeletal functions, especially in areas such as the midface. However, under rare circumstances, extra sutures may present in the midface such as intrazygomatic sutures (incidence of 2.5–6.5% in modern human populations), which arguably would cause unfavorable impact on the ontogeny and biomechanics of the facial skeletons. In this study, the skeletal collection derived from Cayo Santiago (CS) and CS‐derived Rhesus macaque (Macaca mulatta) populations in the Caribbean Primate Research Center was screened for the intrazygomatic sutures. It was hypothesized that the incidence of the intrazygomatic suture in Rhesus macaques was comparable to that in humans. Results demonstrated that, in all examinable skulls with known sex and age information (Total 2483), there are only six specimens that carry intrazygomatic sutures (two Females and four Males; three on left side and three on right side; five with one suture and one with two sutures). Thus, the overall incidence of intrazygomatic sutures in Rhesus macaques, 0.24%, is significantly lower than that in humans (p<0.001). The negative impact of intrazygomatic sutures in the midface needs more biomechanical and morphometric analyses, and insights into this rare condition may deepen our understanding of the craniofacial form and adaptation, and help to improve therapeutic philosophies in corrective and regenerative medicine. Supported by NSF HOMINID BCS‐0725183.

The Developmental Basis of Quantitative Craniofacial Variation in Humans and Mice.

The human skull is a complex and highly integrated structure that has long held the fascination of anthropologists and evolutionary biologists. Recent studies of the genetics of craniofacial variation reveal a very complex and multifactorial picture. These findings contrast with older ideas that posit much simpler developmental bases for variation in cranial morphology such as the growth of the brain or the growth of the chondrocranium relative to the dermatocranium. Such processes have been shown to have major effects on cranial morphology in mice. It is not known, however, whether they are relevant to explaining normal phenotypic variation in humans. To answer this question, we obtained vectors of shape change from mutant mouse models in which the developmental basis for the craniofacial phenotype is known to varying degrees, and compared these to a homologous dataset constructed from human crania obtained from a single population with a known genealogy. Our results show that the shape vectors associated with perturbations to chondrocranial growth, brain growth, and body size in mice do largely correspond to axes of covariation in humans. This finding supports the view that the developmental basis for craniofacial variation funnels down to a relatively small number of key developmental processes that are similar across mice and humans. Understanding these processes and how they influence craniofacial shape provides fundamental insights into the developmental basis for evolutionary change in the human skull as well as the developmental-genetic basis for normal phenotypic variation in craniofacial form.

Nasal septal and craniofacial form in European‐ and African‐derived populations

As a component of the chondrocranium, the nasal septum influences the anteroposterior dimensions of the facial skeleton. The role of the septum as a facial growth center, however, has been studied primarily in long-snouted mammals, and its precise influence on human facial growth is not as well understood. Whereas the nasal septum may be important in the anterior growth of the human facial skeleton early in ontogeny, the high incidence of nasal septal deviation in humans suggests the septum's influence on human facial length is limited to the early phases of facial growth. Nevertheless, the nasal septum follows a growth trajectory similar to the facial skeleton and, as such, its prolonged period of growth may influence other aspects of facial development. Using computed tomography scans of living human subjects (n = 70), the goal of the present study is to assess the morphological relationship between the nasal septum and facial skeleton in European- and African-derived populations, which have been shown to exhibit early developmental differences in the nasal septal-premaxillary complex. First we assessed whether there is population variation in the size of the nasal septum in European- and African-derived samples. This included an evaluation of septal deviation and the spatial constraints that influence variation in this condition. Next, we assessed the relationship between nasal septal size and craniofacial shape using multivariate regression techniques. Our results indicate that there is significant population variation in septal size and magnitude of septal deviation, both of which are greater in the European-derived sample. While septal deviation suggests a disjunction between the nasal septum and other components of the facial skeleton, we nevertheless found a significant relationship between the size of the nasal septum and craniofacial shape, which appears to largely be a response to the need to accommodate variation in nasal septal size.

Masticatory loadings and cranial deformation in Macaca fascicularis: a finite element analysis sensitivity study

Biomechanical analyses are commonly conducted to investigate how craniofacial form relates to function, particularly in relation to dietary adaptations. However, in the absence of corresponding muscle activation patterns, incomplete muscle data recorded experimentally for different individuals during different feeding tasks are frequently substituted. This study uses finite element analysis (FEA) to examine the sensitivity of the mechanical response of a Macaca fascicularis cranium to varying muscle activation patterns predicted via multibody dynamic analysis. Relative to the effects of varying bite location, the consequences of simulated variations in muscle activation patterns and of the inclusion/exclusion of whole muscle groups were investigated. The resulting cranial deformations were compared using two approaches; strain maps and geometric morphometric analyses. The results indicate that, with bite force magnitude controlled, the variations among the mechanical responses of the cranium to bite location far outweigh those observed as a consequence of varying muscle activations. However, zygomatic deformation was an exception, with the activation levels of superficial masseter being most influential in this regard. The anterior portion of temporalis deforms the cranial vault, but the remaining muscles have less profound effects. This study for the first time systematically quantifies the sensitivity of an FEA model of a primate skull to widely varying masticatory muscle activations and finds that, with the exception of the zygomatic arch, reasonable variants of muscle loading for a second molar bite have considerably less effect on cranial deformation and the resulting strain map than does varying molar bite point. The implication is that FEA models of biting crania will generally produce acceptable estimates of deformation under load as long as muscle activations and forces are reasonably approximated. In any one FEA study, the biological significance of the error in applied muscle forces is best judged against the magnitude of the effect that is being investigated.

AR Highlights

The liver plays an important role in the development of organs in the prenatal period. However, morphological and morphometric features of the liver during the early embryonic period are not well understood. Recent advances in medical imaging have enabled earlier assessment of human development in the first trimester. The authors carried out external morphologic and morphometric analysis of the liver during this period using a superparallel magnetic resonance microscope to image embryos obtained from the Kyoto Collection. They determined the external morphology as well as quantitative morphometry of the embryonic liver. They also found that development of the liver was greatly affected by adjacent organs and tissues. The data from this study provide a better understanding of liver development as well as morphogenesis of nearby organs. The authors' results could also be used as a reference for clinical evaluation in the early stage of gestation, and this could be useful in fetal medicine and prenatal diagnosis. The authors predict that further improvement in imaging modalities will enable more precise detection of the intrahepatic vascular system. Natural plants have the potential to produce safe and effective anticancer drugs. E. helioscopia L is a member of the plant family Euphorbiaceae. E. helioscopia L is a traditional Chinese medicine that has been used for centuries to treat various disease conditions, such as tuberculosis, dysentery, cervical carcinoma, and esophageal and lung cancer. The anticancer active fractions and the detailed anticancer mechanism of this herb are not well understood. Therefore, the authors identified the main antitumor active fractions of aqueous-ethanol extracts of E. helioscopia L using five different cancer cell lines in vitro. They found that ethyl acetate and chloroform extracts inhibited proliferation of all five human cancer cell lines and that the ethyl acetate extract was the strongest among four tested. The major active fraction was assayed using high-performance liquid chromatography. The authors found that flavonoids could be the main constituents of the ethyl acetate extract. Electron microscopy results further suggested that ethyl acetate extract of E. helioscopia L may be a potent inducer of apoptosis in cancer cells. The authors also investigated the effects of E. helioscopia L ethyl acetate extract on the invasion and metastasis of a human hepatocellular carcinoma cell line. They found that ethyl acetate extract negatively affected the invasiveness of these cancer cells and that ethyl acetate extract downregulated matrix metalloproteinase-9 (known to play an important role in cancer cell migration and invasion) expression in cancerous cells. Although further studies are required to establish a comprehensive screening of the active constituents of this extract, the authors' results indicate its chemopreventive potential against human cancer. The primary function of sutures in young individuals is to enable growth of the skull. Sutures are morphologically diverse with regard to ontogeny, location, fusion, sexual dimorphism, and intraspecies and interspecies variations. The authors tested the functional hypothesis that sutures act as energy absorbers protecting skulls subjected to dynamic loads. They used a finite element model of a primate cranium (Macaca mulatta) with dynamic simulations to determine the effect of a pair of sutures (zygomaticotemporal) on stress and strain patterns associated with feeding. Feeding is a habitual behavior, which can potentially impose high and/or repetitive loads on the craniofacial skeleton. They scanned the specimen using iCAT cone-beam computed tomography, which is a recently developed technology to evaluate 3D bone morphology at high resolution, and the model was then constructed. This model was simplified structurally to reduce model complexity and to avoid lengthy calculation times during dynamic simulation; therefore, not all of the sutures were modeled. The model also simplified the viscoelastic properties of the sutures. In contrast to expectations and the initial hypothesis, the authors found that zygomaticotemporal sutures play a limited role in modulating global skull mechanics, and they did not absorb significant amounts of energy during dynamic simulations. Based on their study findings, the authors hypothesize that sutures are mechanically significant because they are weak points on the cranium that must be protected from high stresses to avoid disrupting important growth processes. This suggests that sutural protection is an important selective pressure, which may have affected various aspects of sutural and craniofacial form.

Virtual Functional Morphology: Novel Approaches to the Study of Craniofacial Form and Function

Recent developments in simulating musculoskeletal functioning in the craniofacial complex using multibody dynamic analysis and finite elements analysis enable comprehensive virtual investigations into musculoskeletal form and function. Because the growth of the craniofacial skeleton is strongly influenced by mechanical functioning, these methods have potential in investigating the normal and abnormal development of the skull: loading history during development can be predicted and bony adaptations to these loads simulated. Thus these methods can be used to predict the impact of altered loading or modifications of skull form early in ontogeny on the subsequent development of structures. Combining functional models with geometric morphometric methods (GMM), which are principally concerned with the study of variations of form, offers the opportunity to examine variations in form during development and the covariations between form and factors such as functional performance. Such a combination of functional models and GMM can potentially be applied in many useful ways, for example: to build and modify functional models, to assess the outcomes of remodelling studies by comparing the results with morphological changes during ontogeny, and to compare the outcomes of finite element analyses within a multivariate framework. Studies using these tools can not only investigate the development of the skull but also the mechanical processes and thus to some degree, behaviours underlying the development of variation among extant and fossil skeletal elements. By bringing together these tools from quite different comparative traditions, a novel and potentially powerful framework for simulation and statistical biomechanical analyses of form and function emerges. This paper reviews these recent developments in the context of the evolutionary and functional influences on skull development.

The Role of the Sutures in Biomechanical Dynamic Simulation of a Macaque Cranial Finite Element Model: Implications for the Evolution of Craniofacial Form

The global biomechanical impact of cranial sutures on the face and cranium during dynamic conditions is not well understood. It is hypothesized that sutures act as energy absorbers protecting skulls subjected to dynamic loads. This hypothesis predicts that sutures have a significant impact on global patterns of strain and cranial structural stiffness when analyzed using dynamic simulations; and that this global impact is influenced by suture material properties. In a finite element model developed from a juvenile Rhesus macaque cranium, five different sets of suture material properties for the zygomaticotemporal sutures were tested. The static and dynamic analyses produced similar results in terms of strain patterns and reaction forces, indicating that the zygomaticotemporal sutures have limited impact on global skull mechanics regardless of loading design. Contrary to the functional hypothesis tested in this study, the zygomaticotemporal sutures did not absorb significant amounts of energy during dynamic simulations regardless of loading speed. It is alternatively hypothesized that sutures are mechanically significant only insofar as they are weak points on the cranium that must be shielded from unduly high stresses so as not to disrupt vitally important growth processes. Thus, sutural and overall cranial form in some vertebrates may be optimized to minimize or otherwise modulate sutural stress and strain.