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

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.