The role of soft tissues in cranial biomechanics - an investigation using advanced computer modelling techniques

The skull forms a protective shell that encloses the brain and major sense organs. However, it is not an inert structure. During development, the interplay between cranial tissues helps to shape adult skull structure, and even in adult life there is an intimate dialogue between bone and cranial soft tissues that continues to modify and maintain cranial shape. Bone responds to strains, be they from feeding movements/jaw muscles, neck muscles, or the pressures exerted by blood vessels and other structures within the head.

In recent years, the application of mechanical engineering software to biomechanics (by ourselves and others) has increased our understanding of the level and distribution of stresses experienced by the skull by everyday activities. However, it has become clear that the skulls of mammals and reptiles respond in different ways to similar stresses. Part of this difference may relate to skull shape - the enclosed shell-like skull of mammals versus the frame-like skull of many reptiles. However, none of these previous studies have taken into consideration a major component of cranial anatomy - the soft tissues that cover the skull on the one hand and are enclosed by it on the other. Together skull and soft tissues make up what some researchers have deemed a 'functional matrix'. Our objective is to examine the role of different parts of that matrix and determine whether they differ in mammal and reptile skulls.

Our research group is interdisciplinary, with expertise in reptile and mammalian anatomy and evolution, biomechanical engineering, and the analysis of shape in relation to function. We have established a strong track-record and have pioneered an approach that combines the use of dynamic 3-D models (multibody dynamics analysis) and stress analysis (finite element analysis). This yields detailed, anatomically accurate working computer models of animal skulls, including joints (mobile and sutural) and muscles (jaw and neck). Through our previous funded research, we have built up a collection of detailed, anatomically correct, dynamic 3-D models of reptiles and mammals in which the skull, sutures, and both jaw and neck musculature are accurately rendered. These have been validated with in vivo analysis. These models will form the basis for the new project with the addition of accurately rendered soft tissue structures including periosteum, dura and cranial fascia; orbital contents; brain; and oral contents. The data for the anatomical work will be generated by dissection, contrast-stained CT scanning and MRI, and histological examination of fascial fibre types and arrangement.

Consideration of cranial biomechanics and the form and function of skulls has thus far focussed predominantly on the bone - its response to stresses generated in feeding and its role in the protection of the soft cranial contents. However, soft tissues such as the brain and eyes) develop first, becoming enclosed by fibrous capsules (e.g. periosteum, dura) within which the skeletal units ultimately develop and are maintained and shaped. This close integration of hard and soft tissues is understood by craniofacial clinicians, but has received little attention in broader comparative studies. Our aim is to clarify and quantify the role played by apparently inert cranial soft tissues in skull biomechanics and to determine their relative significance in the frame-like reptile skull versus the shell-like skull of mammals.

Our cross-disciplinary research group has pioneered an approach that combines the use of rigid-body modelling (MDA, multibody dynamics analysis), stress analysis (FEA, finite element analysis), and geometric morphometrics. Using this methodology, anatomically accurate working 3-D skull models (MDA) are used to predict joint and muscle forces, that are applied to FE models to predict the skull stress/strain under different feeding conditions. Comparisons with living animals have shown our models to be biologically realistic during biting, with convincing predictions of bite force, bone strain, muscle activation and jaw kinematics. The new project builds on this success with the incorporation of soft tissues (in fact the largest element of cranial contents) into the skull models. The anatomical data will be provided through dissection, histology, MRI, confocal microscopy and scanning electron microscopy. This will complete their construction, making them fully functional and responsive to a wider range of loading scenarios, especially dynamic loads, and increase their scope in comparative studies and more applied, in particular, clinical investigations.

Who will benefit from this research and how?
To maintain its competitiveness, the UK needs a strong science base. To achieve that, we must both enthuse young people to study science and also engage the sympathy and interest of the general public, as stakeholders. Research on animal form and function impacts on each of these goals. Further, as the BBSRC has stated, big challenges require multidisciplinary approaches. That requires young scientists to be trained in an interdisciplinary environment. As a collaboration of bone biologists, engineers and comparative anatomists/ palaeontologists, we offer that training environment. Workshops and one-day meetings facilitate knowledge exchange, benefiting the UK science base as well as attracting overseas students and collaborators. Furthermore, our computational modelling approaches clearly synergise with the Research Councils' 3Rs strategy in relation to reducing usage of animals in experiments.

Project results will interest researchers working on biomechanics and functional/evolutionary morphology. Computer modelling is increasingly used to explore the relationship between skeletal form and function, but non-muscular soft tissues are seldom included.

Our research collaboration (via Fagan) also has good links with craniofacial units at several hospitals (John Radcliffe Hosp., Oxford, the Alderhey Children's Hosp., Liverpool, Great Ormond St, London). The relationship between hard and soft cranial tissues is integral to the management of craniofacial deformities and injuries (e.g. craniofacial synostosis, Moazen et al. 2009b; anophthalmia, microphthalmia, Clauser et al., 2004; Tse et al. 2007; glaucoma and ocular/hypertension related headache, Kumar Gupta et al., 2006; Berdahl et al. 2008; bone repair, hydrocephalus; enophthalmos in orbital floor fracture, Converse & Smith 1957), and a more detailed knowledge of the biomechanical role of different craniofacial tissues will therefore likely impact on treatment programmes (e.g. Buchman et al. 1994; Mao et al. 2003).

The British Science Association has stressed the need to promote greater scientific literacy in the UK, by increasing science levels in schools and promoting greater dialogue between scientists and the public. The skull and skeleton, past and present, are ideal topics in this regard, both in formal learning (as part of the National Curriculum), and amongst the general public, as demonstrated by the popularity of museum visits and the success of TV programmes on natural history, palaeontology, health issues, and anatomy.

What science will it advance?
The application of mechanical engineering techniques to biological problems, although relatively recent, is becoming increasingly sophisticated. Our consortium pioneered the combined use of multi-body dynamics analysis (MDA) and finite element analysis (FEA), as well as bringing tools like DGO and laser interferometry to the field. The advances not only allow detailed modelling of living systems (here in feeding) but also predictive modelling and experimental evolutionary anatomy, whereby morphological changes can be made in silico and their direct effects observed (e.g. Moazen et al. 2009a). The dynamic geometric optimisation (DGO) method developed within our group, for example, offers a way of modelling feeding behaviour in relation to diet in rare and endangered animals for which invasive techniques would be impossible (Curtis et al. 2010a-c). The new project will combine these techniques to address the role of non-muscular cranial soft tissues in skull development, bone maintenance, and cranial function for the first time in an in silico study.

Additional references (not in Case for Support):
Berdahl et al. 2006 Invest Ophthalmol Vis. Sci 49: 5412-5418
Buchman et al. 1994 J Craniofac Surg 5: 2-10
Clauser et al. 2004 J CranioMaxfac Surg 32: 279-290
Converse, Smith 1957 Br J Plast Surg 9: 265
Gupta 2006 MedGenMed. 83: 63