Author's School

School of Engineering & Applied Science

Author's Department/Program

Biomedical Engineering

Language

English (en)

Date of Award

Summer 8-12-2013

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Chair and Committee

Donald L Elbert

Abstract

The biocompatibility of biomaterials is primarily dictated by the interactions that occur at the material's interface with its biological environment. Proteins irreversibly adsorb to these interfaces within seconds to minutes of exposure, altering their structural conformation, inducing cell adhesion, and activating various cellular responses. To this end, surface modification strategies have been designed in attempts to develop "stealth" biomaterials or even biomaterials that modulate this response by inducing specific biological reactions. We sought to advance the design of biomaterial surfaces by quantitatively studying protein adsorption to ultralow protein adsorbing surfaces formed from poly(ethylene glycol) nanogel coatings of variable structural and chemical properties. We found that resistance to protein adsorption can be improved by increasing the nanogel coating's surface packing density, which is achievable using orthogonal cross-linking chemistries, such as click chemistry, under phase separation conditions. We also confirmed that PEG and albumin act synergistically within nanogel coatings to resist protein adsorption. As a demonstration of the utility for such protein resistant surfaces, we fabricated improved cell culture substrates with nanogel coatings, by spatially patterning cell adhesion and functionalizing surfaces with specific ligands. These surfaces showed superior potential for driving the direct reprogramming of fibroblasts to cardiomyocytes over the standard stem cell substratum of Matrigel and revealed insight into optimal cellular organizations for cardiomyocyte differentiation. However, we also unexpectedly found that adsorption of laminin to mercaptosilanated glass promotes a relatively high efficiency of cardiomyocyte differentiation. The findings outlined in this dissertation demonstrate that consideration of often overlooked material design parameters, in addition to the choice of material, provides further opportunity for improving biocompatibility. We further demonstrated that the precision control of cell adhesion and substratum signaling provided by these materials has broad potential in biological applications, including stem cell culture.

DOI

https://doi.org/10.7936/K7QC01G7

Comments

Permanent URL: http://dx.doi.org/10.7936/K7QC01G7

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