Author's School

School of Engineering & Applied Science

Author's Department/Program

Biomedical Engineering

Language

English (en)

Date of Award

January 2009

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Chair and Committee

Donald Elbert

Abstract

Guided by the clinical needs of patients and developments in biology and materials science, the primary focus of the biomaterials field remains at the solid/liquid interface between biomaterial surfaces and biological fluids. For blood-contacting devices, biological responses are initially elicited and directed by proteins that adsorb from this multicomponent solution to form thin films on their surfaces. The identity, conformation, and quantity of adsorbed proteins are related to the properties of a material's surface. For example, hydrophobic surfaces tend to be thrombotic via interactions between platelets and adsorbed fibrinogen, while surface-activation of specific enzymes initiates the coagulation cascade on hydrophilic surfaces. The objective of this thesis is to improve the design of biomaterials through the analysis and control of adsorbing protein layers. This goal is approached through three separate strategies. First, a proteomics-based methodology is presented for the assessment of protein conformation at the residue level after adsorption to biomaterial surfaces. A quantitative mass spectrometric technique is additionally suggested for the identification and quantification of proteins within adsorbed protein layers. Second, a method is described for the covalent attachment of poly(ethylene glycol): PEG)-based hydrogel coatings onto biomaterials surfaces for the minimization of protein adsorption. The coatings are applied using partially crosslinked PEG solutions containing polymer and protein oligomers and microgels that can be designed to control cell adhesion. Finally, a modular strategy is proposed for the assembly of bioactive PEG-based hydrogel scaffolds. This was accomplished using novel PEG microspheres with diverse characteristics that individually contribute to the ability of the scaffold to direct cellular infiltration. The methodologies proposed by this thesis contribute to the recent shift in biomaterials and tissue engineering strategies towards directed cellular responses at the molecular level.

Comments

Permanent URL: http://dx.doi.org/10.7936/K73R0QVN

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