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，是医疗保健服务和患者的主要负担，腰痛是临床实践中最常见的疾病之一，也是多年残疾的主要全球原因。因此，采用多学科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影响的，有助于开发和加强治疗背部损伤和退变的有效装置和疗法。椎间盘的体外力学测试为研究椎间盘损伤和退变机制、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。通常，这些试验的目的是尽可能准确地复制体内条件，然而，脊柱的复杂结构和负载条件意味着简化是必要的。由于没有标准的方法可用，大量的研究限制了他们的测试轴向压缩。本项目旨在创建和研究复杂的和生理相关的负荷分布，以复制日常活动对椎间盘的影响。这些体外试验将使用一种独特的六轴生物载体，该载体目前正在EPSRC资助的项目（EP/S031669/1）中开发。通过在OpenSim中开发和实现肌肉骨骼模型，可以获得不同活动期间的各种负载概况。OpenSim是一个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体骨骼系统的生物力学载荷，否则很难获得，如关节载荷或肌肉力。计算模型提供了一种有吸引力的替代实验方法，其适用性仅限于少数受试者。通过将OpenSim模型与体内数据相结合，可以获得不同日常活动（如步行，坐着，举起）的负荷概况，然后在生物反应器系统中缩放并实现。这个跨学科的项目将整合现有的成像、实验和计算技术，利用所有方法的优势。使用OpenSim模型在不同的日常活动中估计椎间盘上的负荷将导致椎间盘体外测试的各种负荷分布。这些试验可以提供一个新的认识，了解不同的负载如何影响椎间盘细胞的活力和表达。此外，还可以研究由日常任务引起的不同加载方向的影响。这项研究的好处不仅在于它将提供理解，它也有可能在生理学上与测试预防、康复和再生疗法有关，以治疗腰痛。

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.