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

我们的头骨由几块骨头组成，这些骨头通过被称为颅关节或缝合线的软组织沿边缘连接在一起。在婴儿期，我们的头骨在大小和形状上迅速生长，以适应大脑的发育。一旦大脑达到最大尺寸，缝合线处的软组织就会变成骨头来保护我们的大脑，使我们能够更用力地咬。我们对颅骨和颅骨关节在生长过程中所受的力的基本理解是非常有限的。这种知识的缺乏限制了我们推进一系列颅面疾病治疗的能力，这些疾病影响：儿童，如颅缝闭锁是一种由早期颅关节融合引起的医学病症，在过去的30年里，由于未知的原因，整个欧洲的发病率几乎翻了一番。成年人，如大颅骨缺陷，越来越多地用于缺血性中风和创伤性脑损伤的治疗。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空白，同时专注于开发颅缝闭闭（CS）的革命性治疗方法。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），证明了一种治疗的可行性，可以成为21世纪儿童的现实。CranioMech的目标是：(1)进一步扩展我的小鼠治疗，并揭示其作用的基本潜在机制；(2)在更大的动物模型上测试其可扩展性；(3)开展一系列概念验证研究，为首次人体试验做准备，同时揭示当前CS治疗的生物力学原理。这是一个真正的高风险、高收益、多学科、多尺度的项目，结合了基本原理和显著的转化潜力。它将结合先进的方法，如计算机模拟、制造、成像、传感和体内实验，通过解决其未知的机制来改变CS的治疗。这是一个被忽视的领域，与EPSRC医疗技术主题和英国罕见病战略相一致，可以提供平等、多样性、包容性（EDI）和负责任的研究与创新（RRI）的灯塔。

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).