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

揭示颅面系统的力学生物学——寻找一种新的疗法 (CranioMech)

• 批准号: EP/W008092/1
• 负责人: Mehran Moazen
• 金额: $ 197.34万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FW008092%2F1
• 关键词: Unravelling; mechanobiology; craniofacial; system; towards

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 reasonsadults e.g. large calvarial defects increasingly being used for the management of ischaemic stroke and traumatic brain injuryThus, 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).

我们的头骨由几块骨头组成，这些骨头通过称为颅骨关节或缝合线的软组织沿其边缘连接在一起。在婴儿期，我们的头骨的大小和形状迅速增长，以适应大脑的生长。一旦大脑达到最大尺寸，缝合处的软组织就会变成骨头，以保护我们的大脑，并使我们能够更用力地咬合。我们对头骨及其颅关节在生长过程中所承受的力水平的基本了解极其有限。这种知识的缺乏限制了我们推进治疗各种颅面部疾病的能力，这些疾病影响：儿童，例如，儿童。颅缝早闭是一种由颅骨关节早期融合引起的疾病，过去 30 年来，由于不明原因，在欧洲，其发病率几乎翻了一番。大颅骨缺损越来越多地用于治疗缺血性中风和创伤性脑损伤，因此，这是一个巨大的工程挑战，需要使用一系列先进技术进行深入研究。 CranioMech 旨在解决这些工程挑战和我们知识中的关键差距，同时专注于开发一种革命性的颅缝早闭 (CS) 疗法。CranioMech 建立在我的合作者网络和在该领域的良好记录、重要的机构支持（约 69 万英镑）以及我最近的工作（体内小鼠测试）的基础上，该工作证明了一种疗法的可行性，该疗法可能成为 21 世纪儿童的现实 世纪。 CranioMech 的目标是：(1) 进一步扩展我对小鼠的治疗，并揭示其作用的根本机制； （2）在更大的动物模型中测试其可扩展性； (3) 开展一系列概念验证研究，为首次人体试验做准备，同时阐明当前 CS 治疗的生物力学。这是一个真正的高风险、高收益的多学科、多规模项目，将基本原理与巨大的转化潜力相结合。它将使用先进方法的组合，例如计算机模拟、制造、成像、传感和体内实验通过解决 CS 的未知力学来改变 CS 的治疗方法。这是一个被忽视的领域，非常符合 EPSRC 医疗保健技术主题和英国罕见病战略，可以提供平等、多样性、包容性 (EDI) 和负责任的研究和创新 (RRI) 的灯塔。

项目成果

Mechanical loading of cranial joints minimizes the craniofacial phenotype in Crouzon syndrome.

• DOI: 10.1038/s41598-022-13807-9
• 发表时间: 2022-06-11
• 期刊: SCIENTIFIC REPORTS
• 影响因子: 4.6
• 作者: Moazen, Mehran;Hejazi, Mahbubeh;Savery, Dawn;Jones, Dominic;Marghoub, Arsalan;Alazmani, Ali;Pauws, Erwin
• 通讯作者: Pauws, Erwin

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

• DOI: 10.1111/joa.13843
• 发表时间: 2023-06
• 期刊: Journal of anatomy
• 影响因子: 2.4