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

Low back pain 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, in vitro tests aim to replicate in-vivo conditions, however, the complex structure and loading condition of the spine means that simplifications are necessary. 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 bioreactor 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 open-source software. This offers an approach to investigate spinal loading that is 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 to create a diverse range of load profiles for in-vitro culture testing of discs using the bioreactor system. These tests can provide a new understanding of how different load profiles affect the disc cells. 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.