Development of an advanced 3D-engineered neuronal cell culture as a screening tool for drugs promoting peripheral nerve regeneration

INTRODUCTION: Injuries associated with peripheral nerve damage effect ~1 million patients per year. Damage to the peripheral nervous system can be extremely debilitating and result in loss of end organ function, coupled with poor neuron regeneration capacity [1]. Currently the treatment option for injuries are microsurgical and there are no drug therapies available to improve recovery. Pharmacological treatments could potentially be used to maintain neuronal viability, encourage axonal growth, improve axonal specificity to endorgan targets and reduce neuropathic pain. Some drugs and targets have been identified but there are challenges associated with understanding mechanisms of action and moving therapies towards clinical translation. For successful regeneration following injury Schwann cells need to support regeneration and myelination of neurons [2]. This 3D cell-cell interaction is a key feature that needs to be recreated in order to regenerate effective in vitro models. Engineered neural tissue (EngNT) supports the regeneration of neurons within an aligned 3D Schwann cell-seeded collagen gel environment and has the potential to be used as an effective co-culture model. The aim of this study therefore was to develop an assay based on EngNT to analyse the effect of drugs on neurite growth. Initial studies tested the effect of ibuprofen, a drug that has shown some positive effects on nerve regeneration in animal models [3].