Non-specific protein adsorption has a major confounding influence on the in vitro and in vivo performances of synthetic polymer scaffolds for tissue engineering. For control over cell phenotype to be realised, non-specific protein adsorption needs to be constrained and surfaces modified by immobilisation of specific cell attachment and bioactive molecules. Our aim was to develop biodegradable scaffolds incorporating specific bioactive functionalities, whilst at the same time limiting non-specific protein adsorption by the polymer. The approach we developed was to functionalise PLGA scaffolds with diamino-terminated poly(ethylene glycol) (diamino-PEG), followed by the grafting of heparin to the free-NH2 group at the PEG chain end using a coupling agent. The covalent grafting of poly(ethylene glycol) chains both suppressed non-specific protein attachment and provided a substrate for grafting of heparin, onto which growth factors could be tethered and presented to cells in a bioactive configuration. This approach offers a widely applicable solution to overcome the serious and confounding problem of serum fouling of scaffold surfaces, whilst also providing a generic route for specific biofunctionalisation.