Biological fouling of surfaces is problematic for many medical applications because proteins, cells and bacteria can impair the function of devices and lead to catastrophic complications. Numerous strategies exist for reducing fouling in physiological environments; the strategy described in this thesis focuses on the modification of substrates with poly-N-substituted glycine oligomers (polypeptoids) coupled to anchoring peptides inspired by mussel adhesive proteins. Three polypeptoid side-chain compositions were investigated for antifouling performance; polymer-modified TiO2 surfaces were tested for resistance to: adsorption of proteins using optical waveguide lightmode spectroscopy, adhesion of mammalian and bacterial cells using in vitro cell culture methods, and stability to protease enzyme degradation using mass spectrometry and liquid chromatography. The effect of polypeptoid chain length on antifouling properties of the modified surfaces was also investigated by synthesizing poly-N-methoxyethyl glycines with lengths between ten and fifty repeat units. Long-term in vitro cell attachment studies conducted for over one month revealed the importance of polypeptoid side-chain composition and polymer chain length; with a methoxyethyl side chain (15 repeat units or longer) providing superior long-term fouling resistance compared to hydroxyethyl and hydroxypropyl side chains. In an attempt to expand this modification strategy to encompass more relevant biomedical materials, the adsorption conditions were tailored to create thick polymer coatings on synthetic polymer and metal substrates, and resistance to cellular adhesion was confirmed. Adhesion of monocytes and macrophages was studied in order to better understand the inflammatory response that might be elicited by such polymers. Monocyte adhesion on the modified substrates was initially low, suggesting that the necessary integrins for adhesion could not adsorb to the surfaces. To demonstrate additional uses of polypeptoid-modified surfaces, a polypeptoid sequence mimicking helical antimicrobial peptides was appended to the antifouling polymer, and fluorescent microscopy images demonstrated that modified surfaces were capable of damaging the membranes of adherent E. coli. The numerous synthetic variations and modification methods that are explored in this thesis clearly demonstrate that polypeptoid polymers offer promising solutions for surfaces requiring biocompatible and fouling-resistant properties.

Last modified

• 09/08/2018

Creator

• Andrea Ruth Statz

DOI

• https://doi.org/10.21985/N2PF1K

Subject

• Biomedical Engineering

Keyword

• nonfouling
• polypeptoids
• surface modification
• Antifouling
• mussel adhesive proteins
• surface characterization

Date created

• 2008-05-05

Resource type

• Dissertation

Rights statement

• In Copyright