Yucatan miniature pigs, often used as large animal models in clinical research, are distinguished by a breed-specific midfacial hypoplasia with anterior crossbite. Although this deformity can be corrected by distraction osteogenesis, a less invasive method is desirable. We chose a mechanical cyclic stimulation protocol that has been successful in enhancing sutural growth in small animals and in a pilot study on standard pigs. Yucatan minipigs (n = 14) were obtained in pairs, with one of each pair randomly assigned to sham or loaded groups. All animals had loading implants installed on the right nasal and frontal bones and received labels for cell proliferation and mineral apposition. After a week of healing and under anesthesia, experimental animals received cyclic tensile loads (2.5 Hz, 30 min) delivered to the right nasofrontal suture daily for 5 days. Sutural strains were recorded at the final session for experimental animals. Sham animals received the same treatment except without loading or strain gauge placement. In contrast to pilot results on standard pigs, the treatment did not produce the expected sutural widening and increased growth. Although sutures were not fused and strains were in the normal range, the targeted right nasofrontal suture was narrowed rather than widened, with no statistically significant changes in sutural cell proliferation, mineral apposition, or vascularity. In general, Yucatan minipig sutures were more vascular than those of standard pigs and also tended to have more proliferating cells. In conclusion, either because the sutures themselves are abnormal or because of growth restrictions elsewhere in the skull, this cyclic loading protocol was unable to produce the desired response of sutural widening and growth. This treatment, effective in normal animals, did not improve naturally occurring midfacial hypoplasia in Yucatan minipigs.

The neonate skull consists of several bony plates, connected by fibrous soft tissue called sutures. Premature fusion of sutures is a medical condition known as craniosynostosis. Sagittal synostosis, caused by premature fusion of the sagittal suture, is the most common form of this condition. The optimum management of this condition is an ongoing debate in the craniofacial community while aspects of the biomechanics and mechanobiology are not well understood. Here, we describe a computational framework that enables us to predict and compare the calvarial growth following different reconstruction techniques for the management of sagittal synostosis. Our results demonstrate how different reconstruction techniques interact with the increasing intracranial volume. The framework proposed here can be used to inform optimum management of different forms of craniosynostosis, minimising the risk of functional consequences and secondary surgery.

BACKGROUND: Various animal models mimicking craniosynostosis have been developed, using mutant zebrafish and mouse. The aim of this paper is to review the different animal models for syndromic craniosynostosis and analyze what insights they have provided in our understanding of the pathophysiology of these conditions.
METHODS: The relevant literature for animal models of craniosynostosis was reviewed.
RESULTS: Although few studies on craniosynostosis using zebrafish were published, this model appears useful in studying the suture formation mechanisms conserved across vertebrates. Conversely, several mouse models have been generated for the most common syndromic craniosynostoses, associated with mutations in FGFR1, FGFR2, FGFR3 and TWIST genes and also in MSX2, EFFNA, GLI3, FREM1, FGF3/4 genes. The mouse models have also been used to test pharmacological treatments to restore craniofacial growth.
CONCLUSIONS: Several zebrafish and mouse models have been developed in recent decades. These animal models have been helpful for our understanding of normal and pathological craniofacial growth. Mouse models mimicking craniosynostoses can be easily used for the screening of drugs as therapeutic candidates.

Postnatal growth of neurocranium is prevalently completed in the first years of life, thus deeply affecting the clinical presentation and surgical management of pediatric neurosurgical conditions involving the skull. This paper aims to review the pertinent literature on the normal growth of neurocranium and critically discuss the surgical implications of this factor in cranial repair.
A search of the electronic database of Pubmed was performed, using the key word \"neurocranium growth\", thus obtaining 217 results. Forty-six papers dealing with this topic in humans, limited to the English language, were selected. After excluding a few papers dealing with viscerocranium growth or pathological conditions not related to normal neurocranium growth 18 papers were finally included into the present review.
The skull growth is very rapid in the first 2 years of life and approximates the adult volume by 7 years of age, with minimal further growth later on, which is warranted by the remodeling of the cranial bones. This factor affects the outcome of cranioplasty. Thus, it is essential to consider age in the planning phase of cranial repair, choice of the material, and critical comparison of results of different cranioplasty solutions.

Craniosynostosis is a medical condition caused by the early fusion of the cranial joint. The finite element method (FEM) is a computational technique that can answer a variety of \"what if\" questions in relation to the biomechanics of this condition. The aim of this study was to review the current literature that has used FEM to investigate the biomechanics of any aspect of craniosynostosis, being its development or its reconstruction. This review highlights that a relatively small number of studies (n = 10) has used FEM to investigate the biomechanics of craniosynostosis. Current studies set a good foundation for the future to take advantage of this method and optimize reconstruction of various forms of craniosynostosis.

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.

Bones of the cranial vault are formed by the differentiation of mesenchymal cells into osteoblasts on a surface that surrounds the brain, eventually forming mineralized bone. Signaling pathways causative for cell differentiation include the actions of extracellular proteins driven by information from genes. We assume that the interaction of cells and extracellular molecules, which are associated with cell differentiation, can be modeled using Turing\'s reaction-diffusion model, a mathematical model for pattern formation controlled by two interacting molecules (activator and inhibitor). In this study, we hypothesize that regions of high concentration of an activator develop into primary centers of ossification, the earliest sites of cranial vault bone. In addition to the Turing model, we use another diffusion equation to model a morphogen (potentially the same as the morphogen associated with formation of ossification centers) associated with bone growth. These mathematical models were solved using the finite volume method. The computational domain and model parameters are determined using a large collection of experimental data showing skull bone formation in mouse at different embryonic days in mice carrying disease causing mutations and their unaffected littermates. The results show that the relative locations of the five ossification centers that form in our model occur at the same position as those identified in experimental data. As bone grows from these ossification centers, sutures form between the bones.