Date of Award

Summer 6-27-2014

Document Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

First Advisor

Stephanie J. Bryant

Second Advisor

Joel L. Kaar

Third Advisor

Christopher Bowman

Abstract

Tissue engineering aims to replace damaged tissue in the body through the use of cell-laden scaffolds. The scaffold serves as a temporary support for new tissue growth. A particularly promising scaffold material for tissue engineering is poly (ethylene glycol) (PEG)-based hydrogels. These hydrogels are highly tunable, offer facile incorporation of growth factors and cell adhesion moieties to mimic the native extracellular matrix environment, and have been used to encapsulate numerous cell types for tissue engineering. However, the implantation of nearly all synthetic materials elicits a host response, known as the foreign body reaction (FBR). This response is characterized by the presence of activated macrophages and foreign body giant cells, which secrete inflammatory cytokines, enzymes, and reactive oxygen and nitrogen species in an effort to degrade the implant. If the implant persists, it is walled off from the body with an avascular, collagenous fibrous capsule. From a tissue engineering perspective, the early and late stages of the FBR may have adverse consequences on the performance and integration of a tissue engineered construct. The FBR represents a major challenge in using synthetic scaffolds and must be addressed before the full in vivo potential of these materials can be reached. The research presented in this thesis aims to explore the FBR to PEG-based hydrogels and evaluate the effect of encapsulated cells on macrophage activation and the FBR, and the effect of macrophages and the FBR on encapsulated cells. Studies were performed to determine the effect of hydrogel stiffness on macrophage activation and the FBR, and to improve our understanding of the role of protein adsorption in the FBR to PEG-based hydrogels. In addition, studies sought to improve our understanding of the role of protein adsorption in the FBR to PEG-based hydrogels, examine the impact of macrophage activation and the FBR on encapsulated fibroblasts within a PEG hydrogel and vice versa, and investigate the cross-talk between encapsulated mesenchymal stem cells and interrogating macrophages. Finally, work has been done to develop and characterize an enzyme degradable hydrogel, and to the FBR to the material. This thesis provides some of the first analysis of the effect of hydrogel stiffness on the FBR, outlines the mechanism by which PEG hydrogels are inflammatory, and the effect of cross-talk on interrogating macrophages and the FBR.

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