Electrospun fibres with polymer brush coatings for the creation of well–defined cell microenvironments

This thesis presents the development and initial testing of materials that were designed to study interactions between cells and their surrounding environment. These materials form an artificial microenvironment within which a range of properties can be precisely controlled. The materials take the form of polymer microfibres with coatings that allow highly specific stimulation of cells with specific molecules, while simultaneously preventing other non-specific interactions. Fibre matrices were electrospun from two synthetic polymers, developed during the project, that bore initiating groups for surface-initiated atom transfer radical polymerisation (SI-ATRP). The first of these was similar in structure to polystyrene, a non-biodegradable polymer that is used in the majority of cell culture products. The second was derived from poly(ϵ-caprolactone), a biodegradable polymer that is commonly investigated for use in tissue engineering applications. SI-ATRP was then used to create a thin polymer brush coating on the macroinitiator substrates. The monomers used in this polymerisation were chosen to provide the substrates with an increased resistance to protein fouling and non-specific cell adhesion, and to include specific functional groups, with which other molecules could be covalently reacted and thereby attached to the fibres. Specifically, alkyne-bearing monomers were incorporated into the brush coating such that these could be reacted with azide- functional molecules via copper-mediated “click” chemistry. Preliminary studies showed that these substrates supported cell adhesion following the attachment of peptides that bore the arginine-glycine-aspartic acid cell adhesion motif, while surfaces without this peptide consistently resisted cell adhesion.