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

Lead Research Organisation: University College London
Department Name: Cell and Developmental Biology

Abstract

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Technical Summary

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.

Planned Impact

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
 
Description Aspects of the research (especially related to the eyes and to mammals) are still undergoing analysis, although an additional paper on the rabbit is under revision after review. To date our findings include: a) that sutures play a more significant role in lizard skull mechanics than does the cartilaginous braincase (chondrocranium); b) that intraocular pressures recorded in lizards mostly correlate with body size but snakes and gekkotans have unusually high recordings that may be related to the thick spectacle; c) that the lizard postorbital skull experiences much higher strains than the same region in mammals; d) that the mammalian dural folds have, at best, a limited role in cranial stress distribution; e) that the depth and thickness of mammalian dural folds differs considerably between taxa; f) that the postorbital ligament in varanid lizards does not play an important role in skull mechanics, and differences in skull morphology are more important.
Exploitation Route Our BBSRC funded project is linked to a Hull PhD project modelling the relationship of soft and hard tissues in the human skull (after a pilot on the cat). These relationships are relevant to human craniofacial growth, pathology, and injury repair. Evidence of this relevance is the grant awarded to team member Flora Groning: Developing a mixed reality guidance system for reconstructive head and neck surgery. Impact Knowledge Exchange and Commercialisation Award (PI, £2977) for pilot in 2017, followed by grant from Roland Sutton Academic Trust 2017-2020 (PI, £55,038). At UCL, it has also led to a collaboration between a mechanical engineer working on skull biomechanics (Moazen) and a Medical Biophysicist (Bertazzo) on mineralised tissues and the potential of biomimetic materials (with a BBSRC submission on this topic). An extension project on the rabbit skull has recently been financed by BBSRC for a project at Hull University, and we have initiated a joint project with Dr Bruno Simoes, a researcher on comparative eye morphology at the University of Plymouth.
Sectors Healthcare,Culture, Heritage, Museums and Collections,Pharmaceuticals and Medical Biotechnology

 
Description Introducing school students (and undergraduates) to concepts of normal and abnormal skull growth and the relationships of hard and soft tissues. It also has the potential to have applications in relation to craniofacial surgery and repair.
First Year Of Impact 2017
Sector Education,Culture, Heritage, Museums and Collections
Impact Types Cultural,Societal

 
Description Bone structure at the nano-, micro- and macro-scale 
Organisation University College London
Department Mechanical Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution This is a new collaboration between UCL Biosciences and UCL Mechanical Engineering. My lab will contribute anatomical and functional data to a multidisciplinary collaboration looking at the material properties of bone.
Collaborator Contribution Partners are in Mechanical Engineering. One - Dr Moazen - will contribute computational biomechanics (he is a previous collaborator/PhD student); the other Dr Bertazzo is a biomaterials scientist who will bring expertise in bone nano-structure and imaging.
Impact To date - ongoing pilot projects with MSc students on cranial biomechanics and cranial bone nano-structure + Preproposal for Leverhulme Trust for a project on the structure and function of osteoderms - small plates of bone found in the skin of many reptiles. This is a multidisciplinary (morphology, biomechanics, computational mechanics, mechanical enginerring, biomaterials) project that will also involve collaborators in Switzerland (biomaterials) and France (biomechanical testing of live organisms). Full submission not funded, we will resubmit elsewhere. Outcomes in 2016 - one conference poster and one platform talk (Anatomical Society meeting December), both topics being prepared as publications
Start Year 2015
 
Description School talk on skull evolution and the approaches used to study it 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact This was an invited talk to students at Harrow School as part of their science club activities. It introduced them to the interdisciplinary approaches that scientists use in investigating major questions and prompted both questions and discussion
Year(s) Of Engagement Activity 2018
 
Description School widening access event 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Activity by Flora Groning, Aberdeen: Widening access event for S4 and S5 pupils in October and November 2017 on 3D imaging and modelling for medical research, diagnosis and training
Year(s) Of Engagement Activity 2017
 
Description Summer school activity on normal and abnormal skull growth 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Evans worked with Dr Mehran Moazen (a collaborator at UCL) on a school activity related to Dr Moazen's work on modelling craniosynostosis (premature fusion of skull sutures in the developing skull). The school children were given plastic print-outs of CT scanned foetal skulls, disarticulated, and asked to reconstruct them using either wire or elastic to connect bones (simulating flexible versus fused sutures). A balloon was paced inside the reconstructed skull and inflated (simulating brain growth). The children were asked to measure skull dimensions before and after inflation, but with different groups wiring (fusing) different sutures to simulate fusion of the coronal versus sagittal suture in craniosynostosis. This was a way of introducing the children to concepts of skull and brain growth.
Year(s) Of Engagement Activity 2017
 
Description University College London Summer School: Widening Participation. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Public engagement event for Schools: Widening Participation Museums Summer School - Skull workshop. Year 8 (12-13 yrs) pupils x30 June 3rd, 2016. For this we purchased 12 moderate quality plastic skulls on to which the children modelled plasticene muscles, eyes, ears, and dough flesh, to develop the idea of the relationship of hard and soft tissues. Our general aim was that students would gain an understanding of:
- the way hard and soft tissues shape the human face
- the way in which certain features of the skull reflect the attachments of muscles that enable us to bite
- how these features reflect an animal's diet
- that humans, just like all other animals, have features that increase their chances of survival (adaptations).
In Feb/March 2017, in collaboration with the UCL Public Engagement unit, we developed a video version of this activity - narrated by Evans. We piloted this with the same age group of school students in June 2017 and the video now forms part of the Public Engagement groups portfolio for use in schools.
Year(s) Of Engagement Activity 2016,2017,2018