Keele Research Repository

Producing therapeutic neural cell populations in vitro to treat neurodegenerative diseases is a key aim of regenerative medicine. Various protocols have been developed to produce a wide range of neural cell types in vitro, but the protocols are labour and resource intensive. Lower costs will take the cell therapy closer to clinical adoption. Cell-material interactions can be used to control cellular processes and behaviours in the place of expensive reagents. The thesis went about developing superior materials to culture neurons in vitro by using simple surface parameters. By using simple surfaces findings could be leveraged by incorporation in to other materials, and protocols to culture neurons.

We have investigated the responses of primary neural tissue derived from rat ventral mesencephalon (VM), interacting with a range of surface chemical functionalities and net molecular properties by using silanes. Specific substrate functionality leads to higher ratios of neurons, longer neurites and neurosphere spreading capacity. All of these characteristics indicate a high neuro-regenerative capacity.

Next it became important to optimize the amine functionalised surface with the addition of secondary amines in to the surface. The rational of adding secondary amines to the surface would produce functionalities which have a closer resemblance to biological molecules. The biomimicry in the surfaces provides extra scope for selective surface interactions to provide more control over neural cell culture which could steer protocols away from the use of expensive surfaces which are coated in extra cellular matrix molecules such as laminin.

Controlling differentiation with surfaces has long been an aim in regenerative medicine to deliver productive production protocols. It has been shown that surfaces can induce differentiation of stem cells; however there is little control where stem cells and adult cells are
simultaneously cultured. To achieve controlled differentiation of neural stem cells a surface gradient of amine polymer lengths, and polymer densities. That is in contrast to the surfaces used in previous chapters which had homogeneous presentations of surface chemistries.