Spinal cord injury is a devastating trauma that typically induces lifelong paralysis. The poor prognosis for recovery is due to the development of a complex pathophysiology and the release of neurotoxic mediators e.g. the neurotransmitter glutamate. Around the lesion site, damaged cord neurons are particularly susceptible to glutamate-induced excitotoxic damage, which can induce extensive neuronal death secondary to the initial insult. Pharmacological interventions are few and hampered by the need for high dose intravenous delivery and surgical intervention is often needed to stabilise damaged vertebral bones and repair torn dural membranes overlying the injured cord. Taking advantage of an unmet need for a synthetic alternative to the current approach of harvesting tissue from elsewhere in the body to repair the torn dura, researchers at the Royal College of Surgeons in Ireland and University College London have developed an ‘off the shelf’ synthetic polymer-based membranous dural patch for spinal cord injury applications. Designed to be stitched into the torn dural tissues, the patch is drug-loadable due to its novel microscale construction and offers a novel method of ‘locally delivering’ neuroprotective pharmaceutical agents such as Riluzole directly to the damaged cord. Building on this work, the aim of this project is to test the ability of the Riluzole-loaded patch to protect neurons from excitotoxic injury in vitro and secondly, to be able to integrate into host tissues by supporting dural (meningeal) cell growth. Consisting of three objectives spaced over an 8-week experimental period, the project will: identify the optimal loading concentration of Riluzole, test the ability of the patch to slowly elute the drug and protect neurons from chronic glutamate-induced excitotoxic injury and support dural cell growth will be assessed. The data generated from this work will contribute to a publication documenting the development of the patch.
