Investigation into the incorporation of RGD into polymers as a non-integrin selective strategy for tissue engineering.

This thesis describes the development of the 4-bromobenzylsulphonyl (4-
Bbs) group as an enzymatically cleavable protecting group for the side chain of
arginine. The protected arginine was utilised to synthesise RGD peptidcs both
with and without a spacer arm and these peptides were incorporated into
hydrogels. Hydrogels were made from 1,2-propandiol-3-methacrylate (glycerol
methacrylate, GM MA) or butyl methacrylate (BMA) and 1,2-ethandiol
dimethacrylate (ethylene glycol dimethacrylate, EGDMA) and photopolymerized
as 60~m coatings. Removal of the 4-Bbs protecting group was achieved by
incubation with the enzyme Glutathione-S-Transferase.
Culture of human dermal fibroblasts on the materials showed significant
improvements in cell adhesion and viability in serum free media on glycerol
methacrylate hydrogels with nominal RGD concentrations of 1 ~mol/g or greater.
A spacer arm between the peptide and the bulk was not necessary to promote cell
attachment. No significant improvement in cell adhesion and viability to butyl
methacrylate hydrogels was observed at any of the peptide concentrations tested.
The effects of peptide concentration, GST pre-treatment of materials, cell
passage number and culture with soluble RGD were investigated by examining
cell morphology, adhesion, viability and F-actin organisation.