Mimicking the Properties of Scar Tissue in Spinal Cord Injuries

Abstract

Spinal cord injury is a severe condition leading to paralysis below the point of injury, and the healing prospects over time with or without medical intervention are low. The economic costs derived from SCIs are enormous and lifelong. The average lifetime costs of a SCI are estimated around £1.12 million per patient in the United Kingdom. Only a handful of novel treatments are currently being developed and tested, mainly neuroprotective agents and stem cell therapies. As with any other disease or condition, SCI animal models have been invaluable to investigate the efficacy of therapeutic interventions and aim to recreate the pathology of human SCI as closely as possible. Because of the complexity of human SCI, there are no existing models that are able to encompass all aspects of injury in a robust and reproducible manner, which hinders the advance of new treatments. There have been few attempts to replicate the glial scar in vitro, mainly using monolayer cultures or simple three-dimensional alginate/collagen gels. In this work, micro-hollow fibres were utilised to induce cellular alignment like that seen in vivo in the spinal cord. This strategy to induce a defined spatial distribution of neuronal cell types was paired with gellan gum fluid gels with mechanical properties similar to the spinal cord before and after injury as a mimic of the extracellular matrix in the healthy and damaged spinal cord. The results from this project provide a more detailed understanding of the cellular and mechanical features that are seen after trauma in the spinal cord. This knowledge will also improve the research and development of novel therapeutic agents, including cellular therapies, as the platforms developed here will be more representative of the human situation, whilst simultaneously reducing the use of animals.