Hydrogels derived from decellularised tissues for nerve repair

Peripheral nerve injury poses a serious clinical problem, with sensory and motor deficits resulting in significant reductions in patient quality of life. Nerve guidance conduits aim to overcome issues with the current gold standard for repair, the autograft. Recent advances in the field of tissue engineering have allowed for the devlopment of biochemically and physically complex constructs that aim to bridge the injury site to provide an environment that favours regeneration. This thesis explores the possibility of extracellualr matrix (ECM) hydrogels derived from decellularised tissues (dECM-h) and their potential for the maintenance of Schwann cells, ability to form anisotropic cellular tissue, and their subsequent ability to promote in vitro and in vivo neurite extension. A number of tissues were decellularised, biochemical properties assessed, and formed into hydrogels that were mechanically characterised. In vitro screening was then performed to assess Schwann cell metabolic activity, contraction, and alignment within three selected dECM-h. Additionally, stabilised dECM-h seeded with Schwann cells were formed and seeded with dorsal root ganglia to assess their in vitro capabilities to promote neurite extension. Hydrogels derived from decellularised cancellous bone (B-ECM) were found to be appropriate to be taken forward into a rat sciatic nerve transection model to be compared to the currently used purified collagen I derived from rat tails. In vivo axonal regeneration was found to be comparable between the two groups, however did not match that observed in nerve autografts. This study brought a portfolio of decellularised materials from generation, through characterisation and in vitro screening, to selction of one candidate that was taken forward into an in vivo model. This has shown, for the first time, that alternatives to the currently used collagen I hydrogels may be employed in the production and utilisation of engineered neural tissue (EngNT)