Surface modification through atom transfer radical polymerization grafting for the preparation of protein-resistant materials

Surface-initiated atom transfer radical polymerization (ATRP) is a recently developed controlled/living radical polymerization technique for surface grafting of end-tethered polymer chains with controlled pattern, chain length, density, and functionality. These parameters are important in understanding the molecular mechanism of resistance to protein adsorption and cell adhesion to polymer grafted surfaces. The main focus of this thesis is the synthesis of phosphory1choline (PC)- and poly(ethylene oxide) (PEO)-based model surfaces with varying graft densities and chain lengths via surface-initiated ATRP, and the effects of graft density and chain length on their non-biofouling behaviours, including protein adsorption and platelet adhesion.; 2-Methacryloyloxyethyl phosphorylcholine (MPC, MW 295 g/mol) and oligo(ethylene glycol) methyl ether methacrylate (OEGMA, MW 300 g/mol, PEO side chains of average length n = 4.5) were chosen as model monomers containing PC and PEO side chains of comparable length and were grafted on silicon wafer surfaces. The graft density and chain length of poly(MPC) and poly(OEGMA) were controlled via the surface density of the ATRP initiator and the ratio of monomer to sacrificial initiator. The graft density was systematically varied from 0.06 to 0.39 chains/nm2, and the chain length from 5 to 200 monomer units for both poly(MPC)- and poly(OEGMA)-grafted silicon wafer surfaces. The compositions of the grafted surfaces were confirmed by x-ray photoelectron spectroscopy (XPS).; Fibrinogen and lysozyme, two proteins of significantly different size, were used as models to study protein interactions with the grafted surfaces. Adsorption was measured using radiolabelling methods in single protein solutions and binary mixtures in TBS buffer. It was found that adsorption to both poly(MPC) and poly(OEGMA) surfaces decreased with increasing graft density and chain length, and that graft density is more important than chain length in determining protein resistance.; The effect of polymer type, i.e., poly(MPC) versus poly(OEGMA), on protein adsorption was also of great interest since PC and PEO are among the most effective motifs used for modifying surfaces to prevent protein adsorption. It was found, somewhat surprisingly, that for a given chain length and density, adsorption from TBS buffer on both polymer surface types was basically the same.; To investigate further the effect of polymer type on protein adsorption, we determined the water content and thickness of poly(MPC) and poly(OEGMA) layers in D2O using neutron reflectometry. It was found that both poly(MPC) and poly(OEGMA) grafted chains were highly stretched, and that the water fractions in poly(MPC) and poly(OEGMA) layers having similar graft density were comparable. We concluded that the water content of poly(MPC) and poly(OEGMA) layers is strongly correlated to their protein resistance.; The interactions of these surfaces with proteins and platelets in plasma and whole blood were also investigated. These media are more relevant to the application of the surfaces as blood-contacting biomaterials. It was found that both poly(MPC) and poly(OEGMA) surfaces of high graft density (0.39 chains/nm 2) adsorbed identical and extremely low levels of proteins and platelets; however, at low graft density (0.10 chains/nm2), poly(OEGMA) was more effective than poly(MPC) in resisting protein adsorption and platelet adhesion.