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

我们的头骨由几块骨头组成，这些骨头沿着它们的边缘被称为颅骨关节或缝合线的软组织连接在一起。在婴儿期，我们的头骨在大小和形状上迅速增长，以适应我们的大脑发育。一旦大脑达到最大尺寸，缝合处的软组织就会变成骨骼来保护我们的大脑，使我们能够咬得更硬。我们对头骨及其颅骨关节在生长过程中所受的力的基本了解是极其有限的。这种缺乏知识的情况限制了我们推进治疗各种影响儿童的颅面部疾病的能力例如，颅缝融合是一种由早期颅骨关节融合引起的医疗疾病，在过去30年里，由于不明原因在整个欧洲，这种疾病的发病率几乎翻了一番，例如，越来越多的成人使用巨大的颅骨缺损来治疗缺血性中风和创伤性脑损伤因此，这是一项巨大的工程挑战，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，同时专注于开发一种针对颅缝融合(CS)的革命性疗法。CranioMech建立在我的合作者网络和该领域的良好记录、重要的机构支持(约合GB 690k)以及我最近的工作(活体小鼠测试)的基础上，该疗法可能成为21世纪儿童的现实。CranioMech的目标是：(1)进一步扩展我在小鼠身上的治疗方法，并揭示其工作的基本潜在机制；(2)在更大的动物模型中测试其可扩展性；以及(3)开展一系列概念验证研究，为第一次人类试验做准备，同时揭示目前治疗CS的生物力学。这是一个真正的高风险、高收益、多学科、多规模的项目，将基本原则与巨大的翻译潜力结合在一起。它将结合计算机模拟、制造、成像、传感和活体实验等先进方法，通过解决CS的未知机制来改变其治疗方法。这是一个被忽视的领域，非常符合EPSRC Healthcare Technologies的主题和英国针对罕见疾病的战略，该战略可以提供平等、多样性、包容(EDI)和负责任的研究和创新(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).