Directional guidance of neural outgrowth using topography and surface chemistry

Clinical remedies for disorders involving neuronal damage and death that accompany stroke and trauma are not currently available. To develop treatments for these, the ability to control of neurons on surfaces and an understanding of the processes involved is imperative. We are exploring the use of techniques borrowed from the microelectronics industry to make shaped surfaces which we hope, in combination with controlled surface chemistry, will encourage neurons to grow in straight lines and form connections. It is hoped that this will provide useful information on regeneration processes and may in the future even be developed into a therapy to help peripheral nerve regeneration.

This project seeks to explore the hypothesis that enhancement of peripheral nerve regeneration can be achieved by creating a highly ordered Schwann cell matrix using surface topography to act as guidance cues for neural outgrowths. We have recently developed a tool to provide physico chemical surface cues to cells. This consists of a completely tuneable wettability and a range of topographical feature size on each sample in the form of channel and ridge topographies. In preliminary experiments these features have shown promise in guiding model cells (3T3 fibroblast) to move and extend along their length in a region with appropriate surface chemistry and topography. This project seeks to utilise this observation in the field of neuroscience.

We propose to direct outgrowth from neurons by aligning Swann cells on a surface using narrow ridges, which contrasts to the confinement approaches unsuccessfully used to guide neurons on hard surfaces. This has the advantage of both utilising a flexible polymer that can readily be formed and utilising low substrate compliance that has been shown to influence differentiation of stem cells, with soft substrates favouring differentiation into neuronal progenitor cell types.