Directional guidance of neural outgrowth using topography and surface chemistry

Lead Research Organisation: University of Nottingham
Department Name: Sch of Pharmacy

Abstract

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.

Technical Summary

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.

Publications

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Pedersen R (2010) Electron beam lithography using plasma polymerized hexane as resist in Microelectronic Engineering

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Roach P (2010) Chemical Modification of Porous Scaffolds Using Plasma Polymers in Methods in Bioengineering: 3d Tissue Engineering

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Roach P (2010) Surface strategies for control of neuronal cell adhesion: A review in Surface Science Reports

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Roach, P. (2010) Surface Modification and Analysis in Tissue Engineering, book, Editors Martin L. Yarmush and Robert S. Langer

 
Title Perpendicular topographical and chemical gradients for assessing cell-surface interactions 
Description A combinatorial platform having a gradient in chemistry in one direction overlaid orthogonally over a gradient in groove dimensions has been developed. Topographical features were cast in poly(methyl methacrylate) via hot embossing with widths in the range 5-95m, fixed ridge widths of 5 µm and heights of ~ 3 µm. These were then coated firstl with a uniform layer of plasma polymerized poly(allylamine) and subsequently plasma polymerized hexane using a shield to form a gradient by diffusion limited ingress of the polymer during deposition. This resulted in a wettability gradient from a water contact angle of 60to 90 degrees. 
Type Of Material Technology assay or reagent 
Year Produced 2009 
Provided To Others? Yes  
Impact The research is still at the development stage, although potential impacts in understanding the role of surface topography and chemistry in controlling neuronal cell alignment may have impact in regeneration of nervous tissue. 
 
Description Collaboration with Nikolaj Gadegaard at The University of Glasgow 
Organisation University of Glasgow
Department Institute of Molecular Cell and Systems Biology
Country United Kingdom 
Sector Academic/University 
PI Contribution Micro patterned PMMA substrates with graduated feature size have been fabricated in order that we can investigate their application in guiding neuronal cells.
Collaborator Contribution Gadegaard provides advice and materials relating to micro topographical control of cell adhesion to surfaces.
Impact (1) Yang, J.; Rose, F. R. A. J.; Gadegaard, N.; Alexander, M. R. Langmuir 2009, 25, 2567-2571. (2) Yang, J.; Rose, F. R. A. J.; Gadegaard, N.; Alexander, M. R. Advanced Materials 2009, 21, 300-304. (3) Gadegaard, N.; Chen, X.; Rutten, F. J. M.; Alexander, M. R. Langmuir 2008, 24, 2057-2063.
Start Year 2006