A mechanobiochemical investigation into intervertebral disc health - A multidisciplinary approach using in-vivo, in-vitro, and in-silico methods

慢性背部疾病非常常见，是医疗服务和患者的主要负担，而下腰痛是临床实践中遇到的最常见的疾病之一，也是多年来与残疾生活在一起的主要全球原因。因此，一种多学科的方法来更好地评估在各种日常活动中椎间盘是如何受到负荷的影响的，可以帮助开发和增强治疗背部损伤和退变的有效设备和疗法。椎间盘的体外力学测试为研究椎间盘损伤和退变的机制、生物修复策略的机械完整性或医疗器械的疗效提供了有价值的工具。一般来说，这些测试的目的是尽可能准确地复制体内条件，然而，脊柱的复杂结构和加载条件意味着简化是必要的。由于没有可用的标准方法，大量的研究将其测试限制在轴向压缩。这个项目的目的是创建和研究复杂的和生理上相关的负荷分布的影响，这些负荷分布复制了椎间盘上的日常活动。这些体外测试将使用一种独特的六轴生物再生器，该生物再生器目前正在作为EPSRC资助的项目(EP/S031669/1)的一部分开发。通过在OpenSim中开发和实施肌肉骨骼模型，将获得不同活动期间不同范围的负荷分布。OpenSim是一种用于肌肉骨骼建模的开源软件。因此，它提供了一种方法来研究人类骨骼系统上的生物力学载荷，否则很难获得这些载荷，如关节载荷或肌力。与实验方法相比，计算建模提供了一种有吸引力的替代方法，因为实验方法的适用性可能仅限于少数受试者。通过将OpenSim模型与活体数据相结合，可以获得行走、坐着、抬起等不同日常活动的负荷分布，然后在生物反应器系统中进行缩放和实施。这一跨学科项目将利用所有方法的优势整合现有的成像、实验和计算技术。使用OpenSim模型估计不同日常活动期间对椎间盘的负载将导致不同范围的负载分布，用于体外测试椎间盘。这些测试可以为不同的负荷分布如何影响椎间盘细胞的活性和表达提供新的理解。此外，还可以研究日常任务造成的不同加载方向的影响。这项研究的好处不仅是它将提供理解，它还有可能在生理上与测试用于治疗下腰痛的预防、康复和再生疗法相关。

Chronic back conditions are very common and a major burden on healthcare services and patients, and low back pain is one of the most common conditions encountered in clinical practice and is the leading global cause for years lived with disability. A multidisciplinary approach to better evaluate how the intervertebral discs are affected by loading during a variety of daily activities can therefore help in developing and enhancing effective devices and therapies to treat back injuries and degeneration. In-vitro mechanical testing of intervertebral discs provides a valuable tool for investigating mechanisms of disc injury and degeneration, mechanical integrity of biological repair strategies, or efficacy of medical devices. Generally, these tests aim to replicate in-vivo conditions as accurately as possible, however, the complex structure and loading condition of the spine means that simplifications are necessary. As there are no standard methods available a large number of research studies limit their testing to axial compression. This project aims to create and investigate the effect of complex and physiologically relevant load profiles that replicate daily activities on the intervertebral disc. These in-vitro tests will use a unique six-axis biorector that is currently being developed as part of an EPSRC funded project (EP/S031669/1). A diverse range of load profiles during different activities will be obtained through the development and implementation of a musculoskeletal model in OpenSim.OpenSim is an open-source software for musculoskeletal modelling. It therefore offers an approach to investigate the biomechanical loading on the human skeletal system that are otherwise difficult to obtain, such as joint loadings or muscle forces. Computational modelling offers an attractive alternative to experimental methods where the applicability can be limited to only a small number of subjects. By combining an OpenSim model with in-vivo data, load profiles for different daily activities such as walking, sitting, lifting can be obtained and then scaled and implemented in the bioreactor system.This interdisciplinary project will integrate existing imaging, experimental and computational technologies using the advantages of all methods. Estimating the loads on the intervertebral discs during different daily activities using an OpenSim model will lead to a diverse range of load profiles for in-vitro testing of discs. These tests can provide a new understanding of how different load profiles affect the viability and expression of the disc cells. Furthermore, the influence of different loading directions that are caused by daily tasks can be investigated. The benefit of this research is not only the understanding it will provide, it also has potential to be physiologically relevant to test preventative, rehabilitative, and regenerative therapies for treating low back pain.