Engineering oligo(ethylene glycol) based nonfouling surfaces and microstructures for biomedical applications

This thesis presents the initial development of oligo(ethylene glycol) (OEG) based "nonfouling"---protein and cell resistant---coatings that can be applied to a wide range of biomedical applications. The hypothesis underlying this work is that a high density of OEG will eliminate nonspecific protein adsorption thus reduce or eradicate undesired surface phenomena, such as poor biocompatibility, which are direct consequences of the nonspecific protein adsorption. A generalized method for creating functionalized nonfouling surfaces was developed by combining two strategies, namely "Surface-Initiated Atom Transfer Radical Polymerization of Oligo(ethylene glycol) methyl methacrylate (SI-ATRP of OEGMA)" and "Modular design of initiator", demonstrated on gold (metallic materials), glass and silicon oxide (hydroxylated substrates).; SI-ATRP was able to achieve an OEG coating with a density higher than all the pre-existing techniques could achieve. It also provided control over the coating thickness and architecture that are not easily controlled by other techniques. Thickness-density profile of poly(OEGMA) was constructed based on SI-ATRP from mixed SAMs on gold. For the first time, we constructed a map of protein resistance of PEG coated surfaces, which reveals the relationship between the poly(OEGMA) coatings and their protein adsorption. Besides its scientific implications, the practical use (from an engineering point of view) of these results is that the information shall be instructive in designing nonfouling surfaces by providing critical structural parameters.; This thesis also demonstrates integration of SI-ATRP with micro and nano scale pattern fabrication, which further expands the applications of this technology. In vitro cell culturing on patterned surfaces confirmed that high-density OEG coatings were exceptionally nonfouling even in physiological milieu, which shows great promise for the in vivo study of OEG coatings. A prototype protein microarray was fabricated to demonstrate the superior performance of the quasi three dimensional, functionalized nonfouling poly(OEGMA) matrix. A low noise level was achieved as well as a detection limit of bioassay at pg mL-1 level. Preliminary biocompatibility study was demonstrated in in vivo implantation of OEG coated gold substrates into rats. By providing an initial demonstration of the synthesis, characterizations, and prototypical applications of high performance OEG coatings, this thesis creates a sound foundation for future work focused on the optimization of material-specific coating conditions and in vivo biocompatibility study of OEG coated biomedical devices.