Control of ECM organisation and the mechanical environment in a joint 'on a chip' device.

“芯片上的器官”(OOAC)设备为微型化的体外模型提供了新的方法，用于多种组织的共同培养，如关节。这些工具为筛选新的药物靶点以及用于疾病分层和诊断提供了新的生理系统。这些设备在潜在的3D静态和动态环境中组织来自复杂组织的多种细胞类型。有效的生物支架材料的开发依赖于向特定细胞群体提供精确的环境线索来指导其位置和功能的能力。细胞外基质中的纤维等有序的动态纳米结构可以调节细胞在健康和疾病中的行为。利用生物磁性技术，纤维可以在胶原蛋白支架中以定制的方式定位。理解动态环境对联合行为的作用是这些模型的基础。El Haj小组一直在开发创新的方法，利用磁性纳米颗粒(MNPs)在细胞培养模型中传递机械力，工业合作伙伴MICA BiosSystems正在将其开发成一种新产品DYNASCREEN。然而，这种方法也可以用于组织纤维和细胞，这个学生项目旨在建立一种新的合作，以适应技术，为OOAC模型开发组织矩阵。这项工作是对格拉斯哥大学Berry小组开发的新型磁性间充质干细胞球体3D模型的很好补充。带Screen(QMC)的El Haj最近获得了MRC UKRMP项目(2019-2023年)，以设计一个与El Haj持有的专注于设计干细胞利基的现有MRC UKRMP中心(2019-2023年)相一致的“芯片上联合”。这个CDT专业的学生将是一个合作项目，研究芯片设备中通过生物磁学方法在体外传递的有序矩阵和动态加载的新研究领域。该学生将在采购人体组织和确保临床相关性和吸引力方面与我们来自ROH的临床合作主管密切合作。学生将与合作的商业公司、EMULATE(MRC芯片器官项目和QMUL中心的合作伙伴)和MICA BioSystems(DYNASCREEN产品开发)合作，他们正在设计这一领域的新产品，直接与资助项目中正在进行的活动相联系。他们的互动将通过访问他们的研发实验室和培训使用仿真器官芯片和MICA DYNASCREEN系统来实现。

'Organ on a chip' (OOAC) devices provide new approaches to miniaturized in vitro models for co-culture of multiple tissues such as in the joint. These tools offer new physiological systems for screening of new drug targets and for use in disease stratification and diagnostics. These devices organize multiple cell types from complex tissues in potential 3D static and dynamic environments. The development of effective biological scaffold materials for OOAC devices relies on the ability to present precise environmental cues to specific cell populations to guide their position and function.Ordered dynamic nano-scale structures such as fibres in the extracellular matrix can modulate cell behaviors in health and disease. Using biomagnetic strategies, fibres can be orientated in collagen scaffolds in a tailored way. Understanding the role of dynamic environments on joint behaviour is fundamental to these models. The El Haj group has been developing innovative approaches to utilise magnetic nanoparticles (MNPs) to deliver mechanical forces in cell culture models, which is being taken forward into a new product, DYNASCREEN by an industrial partner, MICA Biosystems. However, such approaches can also be adopted for organising fibres and cells, and this student project aims to establish a new collaboration to adapt the technology to develop organised matrices for OOAC models. This work complements well the novel magnetic mesenchymal stem cell spheroid 3D models which has been developed by the Berry group in Glasgow University.El Haj with Screen (QMC) have recently been awarded an MRC UKRMP project (2019-2023) to design a 'joint-on-a-chip' which aligns with an existing MRC UKRMP Hub held by El Haj focused on Engineering the stem cell niche (2019-2023). This CDT student will be an aligned project to investigate a new research area of ordered matrices and dynamic loading delivered through biomagnetic approaches in vitro in the chip devices. The student will work closely with our clinical co-supervisor from ROH in terms of sourcing human tissues and ensuring clinical relevance and pull. The student would work with partner commercial companies, EMULATE (a partner in the MRC Organ on a chip project and QMUL centre) and MICA Biosystems (DYNASCREEN product development) who are designing new products in this area, directly linking with ongoing activity in funded projects. Their interactions will be through visits to their R&D labs and training in the use of the EMULATE organ chips and MICA DYNASCREEN systems.