Functional adaptation of the infant craniofacial system to mechanical loadings arising from masticatory forces.

The morphology and biomechanics of infant crania undergo significant changes between the pre- and post-weaning phases due to increasing loading of the masticatory system. The aims of this study were to characterize the changes in muscle forces, bite forces and the pattern of mechanical strain and stress arising from the aforementioned forces across crania in the first 48 months of life using imaging and finite element methods. A total of 51 head computed tomography scans of normal individuals were collected and analysed from a larger database of 217 individuals. The estimated mean muscle forces of temporalis, masseter and medial pterygoid increase from 30.9 to 87.0 N, 25.6 to 69.6 N and 23.1 to 58.9 N, respectively (0-48 months). Maximum bite force increases from 90.5 to 184.2 N (3-48 months). There is a change in the pattern of strain and stress from the calvaria to the face during postnatal development. Overall, this study highlights the changes in the mechanics of the craniofacial system during normal development. It further raises questions as to how and what level of changes in the mechanical forces during the development can alter the morphology of the craniofacial system.

BounTI (boundary-preserving threshold iteration): A user-friendly tool for automatic hard tissue segmentation.

X-ray Computed Tomography (CT) images are widely used in various fields of natural, physical, and biological sciences. 3D reconstruction of the images involves segmentation of the structures of interest. Manual segmentation has been widely used in the field of biological sciences for complex structures composed of several sub-parts and can be a time-consuming process. Many tools have been developed to automate the segmentation process, all with various limitations and advantages, however, multipart segmentation remains a largely manual process. The aim of this study was to develop an open-access and user-friendly tool for the automatic segmentation of calcified tissues, specifically focusing on craniofacial bones. Here we describe BounTI, a novel segmentation algorithm which preserves boundaries between separate segments through iterative thresholding. This study outlines the working principles behind this algorithm, investigates the effect of several input parameters on its outcome, and then tests its versatility on CT images of the craniofacial system from different species (e.g. a snake, a lizard, an amphibian, a mouse and a human skull) with various scan qualities. The case studies demonstrate that this algorithm can be effectively used to segment the craniofacial system of a range of species automatically. High-resolution microCT images resulted in more accurate boundary-preserved segmentation, nonetheless significantly lower-quality clinical images could still be segmented using the proposed algorithm. Methods for manual intervention are included in this tool when the scan quality is insufficient to achieve the desired segmentation results. While the focus here was on the craniofacial system, BounTI can be used to automatically segment any hard tissue. The tool presented here is available as an Avizo/Amira add-on, a stand-alone Windows executable, and a Python library. We believe this accessible and user-friendly segmentation tool can benefit the wider anatomical community.

Hindlimb kinematics, kinetics, and muscle dynamics during sit-to-stand and sit-to-walk transitions in emus (Dromaius novaehollandiae).

Terrestrial animals not only need to walk and run but also lie prone to rest and then stand up. Sit-to-stand (STS) and sit-to-walk (STW) transitions are vital behaviours little studied in species other than humans so far, but likely impose biomechanical constraints on limb design because they involve near-maximal excursions of limb joints that should require large length changes and force production from muscles. By integrating data from experiments into musculoskeletal simulations, we analysed joint motions, ground reaction forces, and muscle dynamics during STS and STW in a large terrestrial, bipedal, and cursorial bird: the emu (Dromaius novaehollandiae, ∼30 kg). Simulation results suggest that in both STS and STW, emus operate near the functional limits (∼50 % of shortening/lengthening) of some of their hindlimb muscles, particularly in distal muscles with limited capacity for length change and leverage. Both movements involved high muscle activations (> 50 %) and force generation of the major joint extensor muscles early in the transition. STW required larger net joint moments and non-sagittal motions than STS, entailing greater demands for muscle capacity. Whilst our study involves multiple assumptions, our findings lay the groundwork for future studies to understand, for example, how tendon contributions may reduce excessive muscle demands, especially in the distal hindlimb. As the first investigation into how an avian species stands up, this study provides a foundational framework for future comparative studies investigating organismal morphofunctional specialisations and evolution, offering potential robotics and animal welfare applications.

Icex: Advances in the automatic extraction and volume calculation of cranial cavities.

The use of non-destructive approaches for digital acquisition (e.g. computerised tomography-CT) allows detailed qualitative and quantitative study of internal structures of skeletal material. Here, we present a new R-based software tool, Icex, applicable to the study of the sizes and shapes of skeletal cavities and fossae in 3D digital images. Traditional methods of volume extraction involve the manual labelling (i.e. segmentation) of the areas of interest on each section of the image stack. This is time-consuming, error-prone and challenging to apply to complex cavities. Icex facilitates rapid quantification of such structures. We describe and detail its application to the isolation and calculation of volumes of various cranial cavities. The R tool is used here to automatically extract the orbital volumes, the paranasal sinuses, the nasal cavity and the upper oral volumes, based on the coordinates of 18 cranial anatomical points used to define their limits, from 3D cranial surface meshes obtained by segmenting CT scans. Icex includes an algorithm (Icv) for the calculation of volumes by defining a 3D convex hull of the extracted cavity. We demonstrate the use of Icex on an ontogenetic sample (0-19 years) of modern humans and on the fossil hominin crania Kabwe (Broken Hill) 1, Gibraltar (Forbes' Quarry) and Guattari 1. We also test the tool on three species of non-human primates. In the modern human subsample, Icex allowed us to perform a preliminary analysis on the absolute and relative expansion of cranial sinuses and pneumatisations during growth. The performance of Icex, applied to diverse crania, shows the potential for an extensive evaluation of the developmental and/or evolutionary significance of hollow cranial structures. Furthermore, being open source, Icex is a fully customisable tool, easily applicable to other taxa and skeletal regions.

Synchondrosis fusion contributes to the progression of postnatal craniofacial dysmorphology in syndromic craniosynostosis.

Syndromic craniosynostosis (CS) patients exhibit early, bony fusion of calvarial sutures and cranial synchondroses, resulting in craniofacial dysmorphology. In this study, we chronologically evaluated skull morphology change after abnormal fusion of the sutures and synchondroses in mouse models of syndromic CS for further understanding of the disease. We found fusion of the inter-sphenoid synchondrosis (ISS) in Apert syndrome model mice (Fgfr2S252W/+ ) around 3 weeks old as seen in Crouzon syndrome model mice (Fgfr2cC342Y/+ ). We then examined ontogenic trajectories of CS mouse models after 3 weeks of age using geometric morphometrics analyses. Antero-ventral growth of the face was affected in Fgfr2S252W/+ and Fgfr2cC342Y/+ mice, while Saethre-Chotzen syndrome model mice (Twist1+/- ) did not show the ISS fusion and exhibited a similar growth pattern to that of control littermates. Further analysis revealed that the coronal suture synostosis in the CS mouse models induces only the brachycephalic phenotype as a shared morphological feature. Although previous studies suggest that the fusion of the facial sutures during neonatal period is associated with midface hypoplasia, the present study suggests that the progressive postnatal fusion of the cranial synchondrosis also contributes to craniofacial dysmorphology in mouse models of syndromic CS. These morphological trajectories increase our understanding of the progression of syndromic CS skull growth.

A preliminary analysis of replicating the biomechanics of helmet therapy for sagittal craniosynostosis.

PURPOSE: The aim of this study was to investigate the biomechanics of endoscopically assisted strip craniectomy treatment for the management of sagittal craniosynostosis while undergoing three different durations of postoperative helmet therapy using a computational approach. METHODS: A previously developed 3D model of a 4-month-old sagittal craniosynostosis patient was used. The strip craniectomy incisions were replicated across the segmented parietal bones. Areas across the calvarial were selected and constrained to represent the helmet placement after surgery. Skull growth was modelled and three variations of helmet therapy were investigated, where the timings of helmet removal alternated between 2, 5, and 8 months after surgery. RESULTS: The predicted outcomes suggest that the prolonging of helmet placement has perhaps a beneficial impact on the postoperative long-term morphology of the skull. No considerable difference was found on the pattern of contact pressure at the interface of growing intracranial volume and the skull between the considered helmeting durations. CONCLUSION: Although the validation of these simulations could not be performed, these simulations showed that the duration of helmet therapy after endoscopically assisted strip craniectomy influenced the cephalic index at 36 months. Further studies require to validate these preliminary findings yet this study can lay the foundations for further studies to advance our fundamental understanding of mechanics of helmet therapy.

Biomechanical behaviour of lizard osteoderms and skin under external loading.

Many species of lizards are partially enveloped by a dermal armour made of ossified units called osteoderms. Lizard osteoderms demonstrate considerable species-specific variation in morphology and histology. Although a physical/protective role (against predators, prey, conspecifics and impact loading during falls) is frequently advanced, empirical data on the biomechanics of lizard osteoderms are scarce, limiting our understanding of form-function relationships. Here, we report deformation recorded at the surface of temporal osteoderms during controlled external loading of preserved specimens of 11 lizard species (Tiliqua rugosa, Tiliqua scincoides, Corucia zebrata, Pseudopus apodus, Timon lepidus, Matobosaurus validus, Broadleysaurus major, Tribolonotus gracilis, Tribolonotus novaeguineae, Heloderma horridum and Heloderma suspectum). Based on the strain recorded in situ and from isolated osteoderms, the skin of the species investigated can be ranked along a marked stiffness gradient that mostly reflects the features of the osteoderms. Some species such as T. rugosa and the two Heloderma species had very stiff osteoderms and skin while others such as T. lepidus and P. apodus were at the other end of the spectrum. Histological sections of the osteoderms suggest that fused (versus compound) osteoderms with a thick layer of capping tissue are found in species with a stiff skin. In most cases, loading neighbouring osteoderms induced a large strain in the instrumented osteoderm, attesting that, in most species, lizard osteoderms are tightly interconnected. These data empirically confirm that the morphological diversity observed in lizard osteoderms is matched by variability in biomechanical properties.

Enhancing Distraction Osteogenesis With Carbon Fiber Reinforced Polyether Ether Ketone Bone Pins and a Three-Dimensional Printed Transfer Device to Permit Artifact-Free Three-Dimensional Magnetic Resonance Imaging.

OBJECTIVES: To: (1) design an artifact-free 3D-printed MR-safe temporary transfer device, (2) engineer bone-pins from carbon fiber reinforced polyether ether ketone (CFR-PEEK), (3) evaluate the imaging artifacts of CFR-PEEK, and (4) confirm the osteointegration potential of CFR-PEEK, thus enhancing 3D-planning of bony advancements in hemifacial microsomia using sequential magnetic resonance imaging (MRI). STUDY DESIGN: Engineered CRF-PEEK bone pins and a 3D printed ex-fix device were implanted into a sheep head and imaged with MRI and computed tomography . The osseointegration and bony compatibility potential of CFR-PEEK was assessed with scanning electron microscopy images of MC3T3 preosteoblast cells on the surface of the material. RESULTS: The CFR-PEEK pins resulted in a signal void equivalent to the dimension of the pin, with no adjacent areas of MR-signal loss or computed tomography artifact. MCT3 cells adhered and proliferated on the surface of the discs by forming a monolayer of cells, confirming compatibility and osseointegration potential. CONCLUSION: A 3D printed transfer device could be utilized temporarily during MRI to permit artifact-free 3D planning. CFR-PEEK pins eliminate imaging artifact permitting sequential MRI examination. In combination, this has the potential to enhance distraction osteogenesis, by permitting accurate three-dimensional planning without ionizing radiation.

The Significance of Biomechanics and Scaffold Structure for Bladder Tissue Engineering.

Current approaches for bladder reconstruction surgery are associated with many morbidities. Tissue engineering is considered an ideal approach to create constructs capable of restoring the function of the bladder wall. However, many constructs to date have failed to create a sufficient improvement in bladder capacity due to insufficient neobladder compliance. This review evaluates the biomechanical properties of the bladder wall and how the current reconstructive materials aim to meet this need. To date, limited data from mechanical testing and tissue anisotropy make it challenging to reach a consensus on the native properties of the bladder wall. Many of the materials whose mechanical properties have been quantified do not fall within the range of mechanical properties measured for native bladder wall tissue. Many promising new materials have yet to be mechanically quantified, which makes it difficult to ascertain their likely effectiveness. The impact of scaffold structures and the long-term effect of implanting these materials on their inherent mechanical properties are areas yet to be widely investigated that could provide important insight into the likely longevity of the neobladder construct. In conclusion, there are many opportunities for further investigation into novel materials for bladder reconstruction. Currently, the field would benefit from a consensus on the target values of key mechanical parameters for bladder wall scaffolds.

A comparative histological study of the osteoderms in the lizards Heloderma suspectum (Squamata: Helodermatidae) and Varanus komodoensis (Squamata: Varanidae).

We describe the histological appearance of the osteoderms (ODs) of Heloderma suspectum and Varanus komodoensis using multiple staining and microscopy techniques to yield information about their morphology and development. Histological analysis showed that the ODs of H. suspectum are composed of three main tissue types, a superficial layer, herein identified as osteodermine, capping a base composed of Sharpey-fibre bone and lamellar bone rich in secondary osteons (Haversian bone tissue). In contrast, ODs in V. komodoensis are composed of a core of woven bone surrounded by parallel-fibred bone without a capping tissue. Thus, in these two species, ODs differ both in terms of their structural composition and in details of their skeletogenesis. The histology of the mineralised tissues observed in these two reptile taxa provides insights into the mechanism of formation of lizard ODs and presents a direct comparison of the histological properties between the ODs of the two species. These data allow greater understanding of the comparative histological appearance of the dermal bones of lizards and highlight their structural diversity.

Characterizing and Modeling Bone Formation during Mouse Calvarial Development.

The newborn mammalian cranial vault consists of five flat bones that are joined together along their edges by soft fibrous tissues called sutures. Early fusion of these sutures leads to a medical condition known as craniosynostosis. The mechanobiology of normal and craniosynostotic skull growth is not well understood. In a series of previous studies, we characterized and modeled radial expansion of normal and craniosynostotic (Crouzon) mice. Here, we describe a new modeling algorithm to simulate bone formation at the sutures in normal and craniosynostotic mice. Our results demonstrate that our modeling approach is capable of predicting the observed ex vivo pattern of bone formation at the sutures in the aforementioned mice. The same approach can be used to model different calvarial reconstruction in children with craniosynostosis to assist in the management of this complex condition.

Predicting calvarial growth in normal and craniosynostotic mice using a computational approach.

During postnatal calvarial growth the brain grows gradually and the overlying bones and sutures accommodate that growth until the later juvenile stages. The whole process is coordinated through a complex series of biological, chemical and perhaps mechanical signals between various elements of the craniofacial system. The aim of this study was to investigate to what extent a computational model can accurately predict the calvarial growth in wild-type (WT) and mutant type (MT) Fgfr2C342Y/+ mice displaying bicoronal suture fusion. A series of morphological studies were carried out to quantify the calvarial growth at P3, P10 and P20 in both mouse types. MicroCT images of a P3 specimen were used to develop a finite element model of skull growth to predict the calvarial shape of WT and MT mice at P10. Sensitivity tests were performed and the results compared with ex vivo P10 data. Although the models were sensitive to the choice of input parameters, they predicted the overall skull growth in the WT and MT mice. The models also captured the difference between the ex vivoWT and MT mice. This modelling approach has the potential to be translated to human skull growth and to enhance our understanding of the different reconstruction methods used to manage clinically the different forms of craniosynostosis, and in the long term possibly reduce the number of re-operations in children displaying this condition and thereby enhance their quality of life.

Application of Far Cortical Locking Technology in Periprosthetic Femoral Fracture Fixation: A Biomechanical Study.

BACKGROUND: Lack of fracture movement could be a potential cause of periprosthetic femoral fracture (PFF) fixation failures. This study aimed to test whether the use of distal far cortical locking screws reduces the overall stiffness of PFF fixations and allows an increase in fracture movement compared to standard locking screws while retaining the overall strength of the PFF fixations. METHODS: Twelve laboratory models of Vancouver type B1 PFFs were developed. In all specimens, the proximal screw fixations were similar, whereas in 6 specimens, distal locking screws were used, and in the other six specimens, far cortical locking screws. The overall stiffness, fracture movement, and pattern of strain distribution on the plate were measured in stable and unstable fractures under anatomic 1-legged stance. Specimens with unstable fracture were loaded to failure. RESULTS: No statistical difference was found between the stiffness and fracture movement of the two groups in stable fractures. In the unstable fractures, the overall stiffness and fracture movement of the locking group was significantly higher and lower than the far cortical group, respectively. Maximum principal strain on the plate was consistently lower in the far cortical group, and there was no significant difference between the failure loads of the 2 groups. CONCLUSION: The results indicate that far cortical locking screws can reduce the overall effective stiffness of the locking plates and increase the fracture movement while maintaining the overall strength of the PFF fixation construct. However, in unstable fractures, alternative fixation methods, for example, long stem revision might be a better option.

Periprosthetic femoral fracture fixation: a biomechanical comparison between proximal locking screws and cables.

BACKGROUND: The incidence of periprosthetic femoral fractures (PFF) around a stable stem is increasing. The aim of this biomechanical study was to examine how three different methods of fixation, for Vancouver type B1 PFF, alter the stiffness and strain of a construct under various configurations, in order to gain a better insight into the optimal fixation method. METHODS: Three different combinations of proximal screws and Dall-Miles cables were used: (A) proximal unicortical locking screws alone; (B) proximal cables and unicortical locking screws; (C) proximal cable alone, each in combination with distal bicortical locking screws, to fix a stainless steel locking compression plate to five synthetic femora with simulated Vancouver type B1 PFFs. In one synthetic femora, there was a 10-mm fracture gap, in order to simulate a comminuted injury. The other four femora had no fracture gap, to simulate a stable injury. An axial load was applied to the constructs at varying degrees of adduction, and the overall construct stiffness and surface strain were measured. RESULTS: With regards to stiffness, in both the gap and no gap models, method of fixation A was the stiffest form of fixation. The inclusion of the fracture gap reduced the stiffness of the construct quite considerably for all methods of fixation. The strain across both the femur and the plate was considerably less for method of fixation C, compared to A and B, at the locations considered in this study. CONCLUSION: This study highlights that the inclusion of cables appears to damage the screw fixations and does not aid in construct stability. Furthermore, the degree of fracture reduction affects the whole construct stability and the bending behaviour of the fixation.

Periprosthetic femoral fracture--a biomechanical comparison between Vancouver type B1 and B2 fixation methods.

Current clinical data suggest a higher failure rate for internal fixation in Vancouver type B1 periprosthetic femoral fracture (PFF) fixations compared to long stem revision in B2 fractures. The aim of this study was to compare the biomechanical performance of several fixations in the aforementioned fractures. Finite element models of B1 and B2 fixations, previously corroborated against in vitro experimental models, were compared. The results indicated that in treatment of B1 fractures, a single locking plate can be without complications provided partial weight bearing is followed. In case of B2 fractures, long stem revision and bypassing the fracture gap by two femoral diameters are recommended. Considering the risk of single plate failure, long stem revision could be considered in all comminuted B1 and B2 fractures.

Multiscale mechanical characterisation of the craniofacial system under external forces.

Premature fusion of craniofacial joints, i.e. sutures, is a major clinical condition. This condition affects children and often requires numerous invasive surgeries to correct. Minimally invasive external loading of the skull has shown some success in achieving therapeutic effects in a mouse model of this condition, promising a new non-invasive treatment approach. However, our fundamental understanding of the level of deformation that such loading has induced across the sutures, leading to the effects observed is severely limited, yet crucial for its scalability. We carried out a series of multiscale characterisations of the loading effects on normal and craniosynostotic mice, in a series of in vivo and ex vivo studies. This involved developing a custom loading setup as well as software for its control and a novel in situ CT strain estimation approach following the principles of digital volume correlation. Our findings highlight that this treatment may disrupt bone formation across the sutures through plastic deformation of the treated suture. The level of permanent deformations observed across the coronal suture after loading corresponded well with the apparent strain that was estimated. This work provides invaluable insight into the level of mechanical forces that may prevent early fusion of cranial joints during the minimally invasive treatment cycle and will help the clinical translation of the treatment approach to humans.

Comparative analysis of osteoderms across the lizard body.

Osteoderms (ODs) are mineralized tissue embedded within the skin and are particularly common in reptiles. They are generally thought to form a protective layer between the soft tissues of the animal and potential external threats, although other functions have been proposed. The aim of this study was to characterize OD variation across the lizard body. Adults of three lizard species were chosen for this study. After whole body CT scanning of each lizard, single ODs were extracted from 10 different anatomical regions, CT scanned, and characterized using sectioning and nanoindentation. Morphological analysis and material characterization revealed considerable diversity in OD structure across the species investigated. The scincid Tiliqua gigas was the only studied species in which ODs had a similar external morphology across the head and body. Greater osteoderm diversity was found in the gerrhosaurid Broadleysaurus major and the scincid Tribolonotus novaeguineae. Dense capping tissue, like that reported for Heloderma, was found in only one of the three species examined, B. major. Osteoderm structure can be surprisingly complex and variable, both among related taxa, and across the body of individual animals. This raises many questions about OD function but also about the genetic and developmental factors controlling OD shape.

New diagnostic criteria for metopic ridges and trigonocephaly: a 3D geometric approach.

BACKGROUND: Trigonocephaly occurs due to the premature fusion of the metopic suture, leading to a triangular forehead and hypotelorism. This condition often requires surgical correction for morphological and functional indications. Metopic ridges also originate from premature metopic closure but are only associated with mid-frontal bulging; their surgical correction is rarely required. Differential diagnosis between these two conditions can be challenging, especially in minor trigonocephaly. METHODS: Two hundred seven scans of patients with trigonocephaly (90), metopic rigdes (27), and controls (90) were collected. Geometric morphometrics were used to quantify skull and orbital morphology as well as the interfrontal angle and the cephalic index. An innovative method was developed to automatically compute the frontal curvature along the metopic suture. Different machine-learning algorithms were tested to assess the predictive power of morphological data in terms of classification. RESULTS: We showed that control patients, trigonocephaly and metopic rigdes have distinctive skull and orbital shapes. The 3D frontal curvature enabled a clear discrimination between groups (sensitivity and specificity > 92%). Furthermore, we reached an accuracy of 100% in group discrimination when combining 6 univariate measures. CONCLUSION: Two diagnostic tools were proposed and demonstrated to be successful in assisting differential diagnosis for patients with trigonocephaly or metopic ridges. Further clinical assessments are required to validate the practical clinical relevance of these tools.

A physico-mechanical model of postnatal craniofacial growth in human.

Our fundamental understanding of the physico-mechanical forces that drive the size and shape changes of the cranium during ontogeny are limited. Biomechanical models based on finite element method present a huge opportunity to address this critical gap in our knowledge. Here, we describe a validated computational framework to predict normal craniofacial growth. Our results demonstrated that this approach is capable of predicting the growth of calvaria, face, and skull base. We highlighted the crucial role of skull base in antero-posterior growth of the face and also demonstrated the contribution of the maxillary expansion to the dorsoventral growth of the face and its interplay with the orbits. These findings highlight the importance of physical interactions of different components of the craniofacial system. The computational framework described here serves as a powerful tool to study fundamental questions in developmental biology and to advance treatment of conditions affecting the craniofacial system such as craniosynostosis.

The effect of fracture stability on the performance of locking plate fixation in periprosthetic femoral fractures.

Periprosthetic femoral fracture (PFF) fixation failures are still occurring. The effect of fracture stability and loading on PFF fixation has not been investigated and this is crucial for optimum management of PFF. Models of stable and unstable PPFs were developed and used to quantify the effect of fracture stability and loading in a single locking plate fixation. Stress on the plate was higher in the unstable compared to the stable fixation. In the case of unstable fractures, it is possible for a single locking plate fixation to provide the required mechanical environment for callus formation without significant risk of plate fracture, provided partial weight bearing is followed. In cases where partial weight bearing is unlikely, additional biological fixation could be considered.