Devices containing silicone, titanium, stainless steel, and Teflon have been used extensively in medical applications. However, these materials elicit some degree of inflammatory response. Thus, it is desirable to attain control over the surface properties of implantable materials to decrease inflammatory responses and thereby enhance their integration with biological matrices. Previous work on the formation of self-assembled monolayers (SAMs) to engineer materials that resist protein adsorption and cell adhesion focused on modification of gold substrates. This was extended to the immobilization of specific bioligands on bioresistive surfaces to selectively enhance cell adhesion and direct cell function. Although alkanethiol SAMs on gold provide good model systems, they are not robust in vitro or in vivo and rapidly lose the ability to resist cell adhesion.

Titanium and its alloys are frequently used in medical applications such as hip and knee replaces and dental implants because they are strong, lightweight and rarely elicit an inflammatory response. Over time they suffer from loosening and wear due to poor incorporation of the implant into the surrounding bone. To overcome limitations associated with SAMs on gold, this thesis describes the preparation of more robust surface coatings based on polymer brushes on titanium. In this study, we modify titanium substrates with two types of hydrophilic polymer brushes:​ poly(oligo(ethylene glycol) methacrylate) (OEGMA) or poly(gluconoaminoethyl methacrayte) (GAMA) and explored their effect on protein and cell adhesion. The hydroxyl groups of the poly(OEGMA) and poly(GAMA) brushes are amenable to modification with 4-nitrophenyl chloroformate (NPC) to afford 2-nitrophenyl carbonates. Displacement of 4-nitrophenol by amines in peptide sequences affords the ability to immobilize adhesive peptides on the polymer brushes. This allows provides the opportunity to further tailor the interaction between the surfaces and cells by increasing osseointegration of implanted materials.

Titanium substrates bearing poly(OEGMA) brushes resist protein adsorption and cell adhesion for up to two months. The hydroxyl groups on the polymer brushes were functionalized with a peptide fragment, FNIII7-10, which signal for cell adhesion and osteoblast differentiation. The resulting surfaces enhance osteoblast differentiation and increased osseointegration of medical implants during in vitro studies.

Research on poly(GAMA) brushes was motivated by the resistance to protein adsorption afforded by manitol-substituted SAMs. Modification of titanium substrates with poly(GAMA) brushes afforded coatings that resisted protein adsorption and cell adhesion in short-term experiments, but lost resistance within a week in serum. Modification of the hydroxyl groups on poly(GAMA) brushes with an adhesive peptide sequence containing a GFOGER sequence using the NPC strategy enhanced cell adhesion.