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Unravelling the mechanobiology of the craniofacial system- towards a novel therapy (CranioMech)

Lead Research Organisation: UNIVERSITY COLLEGE LONDON
Department Name: Mechanical Engineering

Abstract

Our skulls consist of several bones that are joined together along their edges by soft tissues called cranial joints or sutures. During infancy, our skulls grow rapidly in size and shape to accommodate our brain growth. Once the brain has reached its maximum size, soft tissues at the sutures turn into bone to protect our brain and enable us to bite harder.

Our fundamental understanding of the level of forces that our skulls and its cranial joints experience during the growth is extremely limited. This lack of knowledge has limited our ability to advance treatment of a wide range of craniofacial conditions affecting:

children e.g. craniosynostosis is a medical condition caused by early fusion of cranial joints that has very nearly doubled in incidence across Europe in the last 30 years for unknown reasons

adults e.g. large calvarial defects increasingly being used for the management of ischaemic stroke and traumatic brain injury

Thus, this is a huge engineering challenge that requires in-depth investigations using a range of advanced techniques. CranioMech aims to address these engineering challenges and critical gaps in our knowledge while focusing on developing a revolutionary therapy for craniosynostosis (CS).

CranioMech builds on my network of collaborators and strong track record in this field, significant institutional support (ca. £690k), as well as my recent work (in vivo mouse testing) that demonstrates the feasibility of a therapy that could become a reality for children of the 21st century. CranioMech aims to: (1) further expand on my therapy in mouse and unravel the fundamental underlying mechanism by which it works; (2) test its scalability in larger animal models; and (3) carry out a series of proof of concept studies in preparation for the first human trials, while unravelling the biomechanics of current treatments of CS.

This is a truly high risk, high gain multidisciplinary, multi-scale project, combining fundamental principles with significant translational potential. It will use a combination of advanced approaches e.g. computer simulation, manufacturing, imaging, sensing and in vivo experiments to transform the treatment of CS by resolving its unknown mechanics. This is a neglected area, well in line with EPSRC Healthcare Technologies themes and the UK strategy for rare diseases that can offer a beacon of equality, diversity, inclusion (EDI) & responsible research and innovation (RRI).

Publications

10 25 50

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Cross C (2023) A preliminary analysis of replicating the biomechanics of helmet therapy for sagittal craniosynostosis. in Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery

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Didziokas M (2024) Multiscale mechanical characterisation of the craniofacial system under external forces. in Biomechanics and modeling in mechanobiology

 
Title Journal of Anatomy Dec 2024 front cover (2024) 
Description The cover relate to an automatic segmentation tool that was develop to segment hard tissue on computed tomography images. 
Type Of Art Artefact (including digital) 
Year Produced 2024 
Impact see details in Moazen M, Twigg SRF. 2024. Editorial: Advances in craniosynostosis - Basic science to clinical practice. Journal of Anatomy. 245:813-814. 
URL https://doi.org/10.1111/joa.14126
 
Title Journal of Anatomy June 2023 front cover 
Description Cover image: Three-dimensional meshes of three human crania (in scale) with the inner cavities extracted digitally by the automatic R tool Icex. Upper right, 35 months old female; center left, 19 years old male; lower right, the fossil human cranium Kabwe 1 (also known as Broken Hill 1, often designated as Homo heidelbergensis s.l.). In yellow, brain endocast; in red, frontal sinuses; in orange, orbits; in blue, nasal cavity; in cyan, maxillary sinuses; in violet, upper oral cavity. The brain endocasts have been extracted by the R tool endomaker.' See C. Buzi et al, 'Icex: advances in the automatic extraction and volume calculation of cranial cavities' 
Type Of Art Artefact (including digital) 
Year Produced 2023 
Impact This front cover featured a journal article that we published in this journal effectively describing a novel open source (R tool) to extract intracranial cavities. This code has been widely use by our team and the wider community globally. The cover simply increased the impact of this work. 
 
Title Journal of Anatomy March 2023 front cover 
Description Cover image: see Y. Hoshino et al., 'Synchondrosis fusion contributes to the progression of postnatal craniofacial dysmorphology in syndromic craniosynostosis'. 
Type Of Art Artefact (including digital) 
Year Produced 2023 
Impact Front cover featured a journal article that we published in this journal. The cover increased the impact of this study highlighting the contribution of cranial base joints to the craniofacial morphology a crucial and under-investigated area. 
 
Description This award is still ongoing one major outcome so far is an innovative open access software/program that has been released to enable researcher to convert medical images to meaningful 3D models for various analysis. We have tested this on a number of craniofacial systems and results are extremely positive.
Exploitation Route This award is still ongoing but at present there are a number of ways that its outcome can be taken forward for a number of areas such as craniofacial mechnobiology, craniofacial evolution and developing therapeutic technologies to advance treatment of craniosynostosis and perhaps other conditions.
Sectors Healthcare

 
Description We are working closely with Headlines Craniofacial charity (patients) and a number of hospitals (inter/nationally - clinicians and patients) to use our methodologies and technologies for various clinical, education and patient benefits.
First Year Of Impact 2024
Sector Healthcare
Impact Types Societal

Policy & public services

 
Description Contributed to the Human Frontiers Science Program (HFSP) High-level Science Summit (Paris- France)
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a guidance/advisory committee
 
Description Membership of BioMedEng council
Geographic Reach National 
Policy Influence Type Participation in a guidance/advisory committee
 
Description Membership of UKRI Interdisciplinary Assessment College (IAC)
Geographic Reach National 
Policy Influence Type Participation in a guidance/advisory committee
 
Description Mentoring for RAEng Graduate Engineering Engagement programm
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
 
Description Trustee of Headlines Craniofacial Support
Geographic Reach National 
Policy Influence Type Participation in a guidance/advisory committee
 
Description Disease Models & Mechanisms - The Company of Biologists travel grant for Dr Ce Liang
Amount € 600 (EUR)
Organisation Company of Biologists 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2024 
End 04/2024
 
Description LymphMotion - Revolutionizing lymphoedema treatment
Amount £75,000 (GBP)
Funding ID EF-2223-17-164 
Organisation Royal Academy of Engineering 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2024 
End 12/2024
 
Description Maria-Bitner Glindzicz Early Career Research Award for Miss Miranda Steacy
Amount £500 (GBP)
Organisation University College London 
Department Great Ormond Street Institute of Child Health
Sector Public
Country United Kingdom
Start 02/2024 
End 02/2024
 
Description Research project - Optimizing skull reconstruction of children requiring posterior cranial vault expansion
Amount £70,936 (GBP)
Funding ID PGS22/100040 
Organisation Rosetrees Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 08/2023 
End 08/2026
 
Description The Genetic Society travel grant for Dr Tengyang Qiu
Amount £750 (GBP)
Organisation The Genetics Society 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2024 
End 07/2024
 
Title Icex: Advances in the automatic extraction and volume calculation of cranial cavities 
Description 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 
Type Of Material Model of mechanisms or symptoms - in vitro 
Year Produced 2023 
Provided To Others? Yes  
Impact This R code enables automatic characterization of craniofacial volumes such as intracranial volume and eyes. 
 
Title Average models of human skull at different ages from 0-4 years 
Description .stl files of average models of skull at different ages from 0-4 years of age resulted from analysis of over 200 skulls in that age range were made available open access. 
Type Of Material Database/Collection of data 
Year Produced 2023 
Provided To Others? Yes  
Impact .stl files of average models of skull at different ages from 0-4 years of age resulted from analysis of over 200 skulls in that age range were made available open access. 
URL https://moazenlab.com/resources/
 
Description Alder Hey Children's Hospital Trust, Liverpool, UK 
Organisation Alder Hey Children's Hospital
Country United Kingdom 
Sector Hospitals 
PI Contribution We are exchanging data and knowledge to improve clinical management of craniosynostosis.
Collaborator Contribution Providing clinical insight and data to enable us to develop advanced computational models and analysis clinical data to inform clinical practice for patient benefit
Impact a journal article is being drafted at present
Start Year 2024
 
Description Department of Plastic Surgery - University of Gothenburg 
Organisation University of Gothenburg
Department Sahlgrenska Academy
Country Sweden 
Sector Academic/University 
PI Contribution Prof Lars Kolby provided us CT data for patients who had undergone a specific surgery that we used to compare with a range of other techniques and used to develop validated computational models of skull growth.
Collaborator Contribution Prof Lars Kolby provided us CT data for patients who had undergone a specific surgery that we used to compare with a range of other techniques and used to develop validated computational models of skull growth.
Impact Several journal articles and conference presentation have been resulted from this collaboration.
Start Year 2020
 
Description Department of Plastic Surgery - University of Gothenburg 
Organisation University of Gothenburg
Department Sahlgrenska Academy
Country Sweden 
Sector Academic/University 
PI Contribution Prof Lars Kolby provided us CT data for patients who had undergone a specific surgery that we used to compare with a range of other techniques and used to develop validated computational models of skull growth.
Collaborator Contribution Prof Lars Kolby provided us CT data for patients who had undergone a specific surgery that we used to compare with a range of other techniques and used to develop validated computational models of skull growth.
Impact Several journal articles and conference presentation have been resulted from this collaboration.
Start Year 2020
 
Description Hôpital Necker Enfants-Malades 
Organisation Necker-Enfants Malades Hospital
Country France 
Sector Hospitals 
PI Contribution A large set of CT data have been analysed by us at moazenlab.
Collaborator Contribution A large set of CT data have been collected and provided to us also a team member from this group has been travelling and spending time in moazenlab to help us analysing these data.
Impact This is a multi-disciplinary collaboration and several conference presentations and publications have been resulted and are in progress associated with this collaboration.
Start Year 2016
 
Description Institut Català de Paleoecologia Humana i Evolució Social (IPHES-CERCA), Universitat Rovira i Virgili, Tarragona - Costantino Buzi 
Organisation Rovira i Virgili University
Country Spain 
Sector Academic/University 
PI Contribution Dr Buzi spent 2-3 months in our group, developing and testing a code to automatically segment various craniofacial volumes. We provided the imaging data and also trained him on using finite element method to unravel the mechanics of craniofacial system.
Collaborator Contribution Dr Buzi carried out the programming of the code and the results of which is now published and is available open access.
Impact an open access code and a journal article.
Start Year 2023
 
Description Institut Català de Paleoecologia Humana i Evolució Social (IPHES-CERCA), Universitat Rovira i Virgili, Tarragona - Federica Landi 
Organisation Rovira i Virgili University
Country Spain 
Sector Academic/University 
PI Contribution Dr Landi spent ca. 1 month with us in MoazenLab. We share our imaging data with her and trained her using finite element method and our approach to predict craniofacial growth.
Collaborator Contribution Dr Landi contributed to our work given her knowledge of masticatory muscles and how to quantify physical-cross sectional area of various craniofacial muscles to include in our finite element model of craniofacial growth.
Impact a journal articles in under review.
Start Year 2023
 
Description Oxford Craniofacial Unit 
Organisation Oxford University Hospitals NHS Foundation Trust
Department OXFORD CRANIOFACIAL UNIT
Country United Kingdom 
Sector Hospitals 
PI Contribution We are advising/sharing our models and its outcomes with this group.
Collaborator Contribution Moazenlab members have been visiting this group to advance their understanding of the clinical condition and the social-economical challenges that patients with this condition face. This is also invaluable for our students to develop realistic computational models to inform the clinical practice.
Impact Several join conference presentations and journal publications have resulted from this collaboration and are in progress.
Start Year 2013
 
Description Radboud UMC team 
Organisation Radboud University Nijmegen Medical Center
Country Netherlands 
Sector Academic/University 
PI Contribution advising on helmet treatment being used at Radboud.
Collaborator Contribution several meeting exchanging experience and data to model helmet therapy for treatment of sagittal synostosis.
Impact we are carrying out various simulations results of which will be included in Mr Cross thesis and will be prepared for a journal article.
Start Year 2021
 
Description School of Dentistry - University of Washington 
Organisation University of Washington
Department School of Dentistry Washington
Country United States 
Sector Academic/University 
PI Contribution We are exchanging computed tomography data, knowledge and carry out in vivo animal experiment at University of Washington.
Collaborator Contribution Enabling in vivo large animal experiment at their institution as well as sharing data and knowledge with us.
Impact Several joint publications are under preparation.
Start Year 2022
 
Title Automatic hard tissue segmentation (BounTI) 
Description please see Didziokas M, Pauws E, Kolby L, Khonsari RH, Moazen M. 2024. BounTI (Boundary-preserving Threshold Iteration): a user-friendly tool for automatic hard tissue segmentation. Journal of Anatomy. 245:829-841. 
Type Of Technology Webtool/Application 
Year Produced 2024 
Open Source License? Yes  
Impact This tool is benefiting a large number of ongoing research in Moazen lab and world wide and has already results in several follow on projects and collaboration where researchers are using this tool for their research or have further developed it 
URL https://moazenlab.com/resources/
 
Description A conference talk - European Society of Biomechanics, Edinburgh, UK (Dr Liang) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Liang C, Marghoub A, Profico A, Buzi C, Johnson D, Khonsari RH, O'Higgins P, Moazen M. 2024. Characterising and predicting normal postnatal craniofacial growth and development in human. European Society of Biomechanics, Edinburgh, UK
Year(s) Of Engagement Activity 2024
 
Description A conference talk - European Society of Biomechanics, Edinburgh, UK (Mr Didziokas) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Didziokas M, Steacy M, Qiu T, Marghoub A, Katudampe Vithanage D, Liang C, Alazmani A, Pauws E, Moazen M. 2024 Computational models from automatically segmented CT data - mouse craniofacial system. European Society of Biomechanics, Edinburgh, UK
Year(s) Of Engagement Activity 2024
 
Description A poster presentation - GRC Craniofacial Morphogenesis and Tissue Regeneration, Barcelona, Spain (poster) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Liang C, Marghoub A, Profico A, Buzi C, Johnson D, Khonsari RH, O'Higgins P, Moazen M. 2024. Characterising and predicting normal postnatal craniofacial growth and development in human. GRC Craniofacial Morphogenesis and Tissue Regeneration, Barcelona, Spain (poster)
Year(s) Of Engagement Activity 2024
 
Description A talk or presentation - GRC Craniofacial Morphogenesis and Tissue Regeneration, Barcelona, Spain (invited talk) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Didziokas M, Steacy M, Qiu T, Katudampe Vithanage D, Liang C, Pauws E, Moazen M. 2024. Mechanics of the mouse craniofacial system under external loads. GRC Craniofacial Morphogenesis and Tissue Regeneration, Barcelona, Spain (invited talk)
Year(s) Of Engagement Activity 2024
 
Description Anatomical Society, UK - Marius Didziokas (talk) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Didziokas M, Pauws E, Kölby L, Khonsari RH, Moazen M. 2024. An automated craniofacial segmentation tool: BounTI. Anatomical Society Winter meeting, Liverpool, UK
Year(s) Of Engagement Activity 2024
 
Description Best Journal of Anatomy paper talk - Anatomical Society Winter meeting (Miss Steacy) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Hoshino, Y., Takechi, M., Moazen, M., Steacy, M., Koyabu, D., Furutera, T., Ninomiya, Y., Nuri, T., Pauws, E., Iseki, S. 2025. Synchondrosis fusion contributes to the progression of postnatal craniofacial dysmorphology in syndromic craniosynostosis. Anatomical Society Winter meeting, Preston, UK [best paper presentation]
Year(s) Of Engagement Activity 2024
 
Description BioMedEng23, UK - Ce Liang (talk) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact Liang C , Marghoub A, Profico A, Buzi C, Khonsari RH , Johnson D , O'Higgins P, Moazen M. 2023. A physico-mechanical model of postnatal craniofacial growth in human 0-48 months. BioMedEng23, Swansea, UK
Year(s) Of Engagement Activity 2023
 
Description BioMedEng23, UK - Marius Didziokas (poster) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact Didziokas M, Jones D, Alazmani A, Steacy M, Pauws E, Moazen M. 2023. Quantifying mechanical strain that can prevent early cranial joint suture fusion in a genetically modified mouse. BioMedEng23, Swansea, UK.
Year(s) Of Engagement Activity 2023
 
Description First conference of Young Person Network of Headlines Craniofacial Support 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact 2024-09-21 Together with Young Person Network of Headlines Craniofacial Support, researches from Profs Moazen, Liu and Twigg, organised the first conference of this network. The day brought together researchers working on different aspects of craniosynostosis and those affected by this condition. Researchers shared their work in three hands on activities while those affected by craniosynostosis shared their life stories. We all had an amazing day a huge thanks to all involved and UKRI EPSRC & MRC for supporting the event.
Year(s) Of Engagement Activity 2024
URL https://moazenlab.com/news/
 
Description International Society of Craniofacial Surgeons 2023, USA - Ce Liang (talk) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Liang C , Marghoub A, Profico A, Buzi C, Khonsari RH , Johnson D , O'Higgins P, Moazen M. 2023. A physico-mechanical model of postnatal craniofacial growth in human 0-48 months. International Society of Craniofacial Surgeons 2023, Seattle, USA.
Year(s) Of Engagement Activity 2023
 
Description Organized 3rd "Advances in Craniosynostosis - Basic Sciences to Clinical Practice" 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact We organized the 3rd "Advances in Craniosynostosis - Basic Sciences to Clinical Practice". This event brought together about 100 individuals from across the world with different backgrounds working on various aspects of a medical condition called craniosynostosis to share their experience and knowledge.
Year(s) Of Engagement Activity 2023
 
Description volunteering as a placement host for the In2STEM programme 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact 2024 July- Aug volunteering as a placement host for the In2STEM programme
Year(s) Of Engagement Activity 2024