A tool for investigating cell-material interactions: surface chemical and topographical gradients

An understanding of the factors influencing cell-surface interactions is important in tissue engineering and the field of biomaterials. Cellular interactions with synthetic surfaces are critically dependent on surface chemistry and topography, although attempts to develop general relationships based for example on surface wettability, are often frustrated by exceptions for certain chemical functionality or cell type. It is the realisation that many cell types and surface chemistry must be sampled in order to fully characterise the factors influencing cell response to surfaces that leads us to look to a high throughput approach to this area. We propose a method to produce a large number of combinations of topographical feature size and polymeric composition on one sample. This will allow cellular response to be determined in a high throughput manner, enabling efficient development of predictive quantitative cell-surface relationships. We propose coating a gradient in topographical feature size with a plasma polymer gradient in chemistry that is oriented perpendicular to each other enabling cell response at a certain position to be correlated with the unique local combination of chemistry and topography. Successful development of this revolutionary approach will represent a major advance in the way we investigate cell interactions with surfaces and in the proposal we highlight some ways these results will be applicable in the field of tissue engineering.

Substrate factors identified in the literature as important in determining cell response to synthetic materials are surface chemistry (rationalised as wettability or chemical functional composition), topography and compliance. However, a full understanding of any one of the factors is lacking and their interrelationship is almost completely unexplored because of the shortage of surfaces of both controllable chemistry and topography on which to study cell response. Traditionally, the study of cell response to materials involves culture on the surface of a material resulting from previous processing steps, e.g. a woven synthetic vascular graft or supercritical carbon dioxide foamed tissue engineering scaffold. These have topography and surface chemistry dictated by fibre diameter related to weaving and liquid leakage concerns and supercritical carbon dioxide processing parameters respectively. The surface structure is produced as a consequence of these factors rather than rational design to optimise performance. When the chemistry and topography of materials are specifically investigated, cells are either cultured on a number of samples with the same topography but different chemistry, or on varied topographical feature size on a substrate of only one chemistry. In the later case the topography is often roughness, controlled in a way that usually alters the chemistry preventing total delineation of the two factors. Such studies necessary have a low-throughput, in that each parameter is tested on a separate sample, which is not time or cost efficient. Thus, here we propose development of an as-yet unproved idea involving superimposition of a gradient in chemistry on a perpendicular gradient in topographical feature size.