Modelling the osteocyte network and its control of the mechanotransduction and remodelling of bone

骨是一种非凡的材料，它经历了生长和发育到成熟的初始阶段，然后在其剩余的生命中/通过称为“重塑”的过程进行持续的修复，更新和优化循环。令人惊讶的是，控制骨重建的机制仍然没有完全理解;但众所周知，它们非常复杂，并且随着使用、年龄、疾病和其他因素而变化。观察到骨随着时间的推移对其所经历的负荷作出反应，因此，如果骨反复过载，则骨变厚，如果骨使用不足，则骨吸收。特殊的负荷传感细胞（骨细胞）网络分布在整个骨骼中，负责检测施加的负荷，并触发开始形成新骨或去除现有骨的事件。因此，骨细胞网络在控制骨重建和维持骨骼效率方面起着关键作用，本研究的目的是研究如何将最新的控制工程方法（例如，用于控制飞机和其他复杂系统）应用于骨细胞网络，并创建骨重建的模拟。这种模拟将是一种非常有价值的工具，使研究人员能够探索骨骼在健康、患病或受伤时的工作方式。例如，人们可能会推测，骨质疏松症中观察到的骨密度降低是因为骨细胞网络以某种方式受损或骨细胞的敏感性改变。这些理论可以在控制模型模拟中进行检查，以检查它们是否产生了骨质疏松症的症状，同样，控制模型模拟可以用于检查不同治疗方法对病情的影响。其他应用可能包括开发新的植入物或开发组织工程学的新概念;例如，用于骨组织修复的支架或促进骨生长的生物活性植入物。在该项目的后期，基于我们在这项工作中的经验，我们将寻求确定生物学和生命科学的其他领域，控制工程可能有助于解释和研究其他复杂现象。此外，我们将研究是否特殊的功能和性能的控制系统调节骨重塑可能更广泛地适用于工程，并提供新的和/或不寻常的控制系统的想法。

Bone is a remarkable material which goes through an initial phase of growth and development to maturity, followed by a continuous cycle of repair, renewal and optimisation throughout the rest of its life / by a process called 'remodelling'. Surprisingly, the mechanisms controlling bone remodelling are still not completely understood; but it is known, that they are very complex and change with use, with age, with disease and with other factors. Bone is observed to react to the load it experiences over time, so that it thickens if it is repeatedly over-loaded and resorbs if it is under-used. A network of special load sensing cells (osteocytes) is distributed throughout the bone and is responsible for detecting the applied load, and triggering the events that start the formation of new bone or the removal of existing bone. Thus the osteocyte network plays a key role in controlling the bone remodelling and maintaining the efficiency of our skeletons.The aim of this research is examine how the latest control engineering methods (for example, used to control aircraft and other complex systems) might be applied to the osteocyte network / and to create a simulation of bone remodelling. Such a simulation would be an extremely valuable tool and allow researchers to explore how bone works when it is healthy, diseased or injured. For example, one might speculate that the decrease in bone density observed with osteoporosis occurs because the osteocyte network somehow gets damaged or the sensitivity of the osteocytes is altered. These theories could be examined in the control model simulation, to examine whether they produced the symptoms observed with osteoporosis, and similarly the control model simulation could be used to examine the effects of different treatments for the condition. Other applications would might include the development of new implants or exploitation of new concepts in tissue engineering; for example, scaffolds for bone tissue repair or bioactive implants that encourage bone growth.Later on in the project, based on our experience with this work, we will seek to identify other areas in biology and the life sciences in general, where control engineering might be useful to explain and examine other complex phenomena. Furthermore, we will examine whether the special features and properties of the control system regulating bone remodelling might be more widely applicable to engineering, and provide ideas for new and/or unusual control systems.