Date of Award

December 2015

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical and Chemical Engineering

Advisor(s)

James H. Henderson

Second Advisor

Patrick T. Mather

Keywords

Bone, Cell Culture, Cell Tracking, Mechanobiology, Shape Memory Polymer, Tissue Engineering

Subject Categories

Engineering

Abstract

Tissue engineering is a promising, fast-growing field that combines cells, signals, and scaffolds to regenerate damaged tissues. To develop new, functional, engineered tissues, it is becoming increasingly important to understand how cell-material interactions affect the cell mechanobiological response. As a result, recent efforts have focused on developing complex synthetic materials that can mimic the dynamic in vivo cell environment. In this work, shape memory polymers (SMPs) were employed to develop dynamic 2D substrates and 3D scaffolds that undergo programmed changes in shape under cell compatible conditions. These substrates and scaffolds were applied in vitro and in vivo to demonstrate their potential as platforms to study cell mechanobiology and as functional tissue engineered constructs.

The first part of this dissertation describes the fabrication and application of an SMP bilayer system capable of forming nano-scale wrinkles under cytocompatible conditions. Wrinkled substrates with easily tunable characteristics were employed to control the degree of cell alignment, with increased wrinkle amplitude and wrinkle orientation resulting in increased cell alignment until reaching a point of saturation. Active wrinkling with attached and viable cells was found to enable cell alignment to be “turned-on” on command. Additionally, cell migration on wrinkled substrates was assessed using quantitative, statistical-physics-based metrics which revealed cell motility atop anisotropic wrinkled substrates and which was more oriented and persistent than cell motility atop flat isotropic controls

The second part of this dissertation describes the fabrication and application of porous 3D SMPs capable of expanding under physiological temperatures. A modified porogen-leaching approached was employed to fabricate highly porous, interconnected SMP scaffolds with tunable properties. The potential of SMP foams for use as synthetic bone substitutes was demonstrated in a mouse segmental defect model, where expanding foams were deployed intraoperatively to fill and conform to a critical size defect. Stiff SMP foams were able to maintain defect stability in a load-bearing application and integrated with the native bone after 12 weeks. Furthermore, deployable SMP foams showed potential for use as deployable cell-based therapies to facilitate bone repair, as expanding foams were able to support osteogenic differentiation of attached stem cells.

This work demonstrates the potential of SMPs to be employed as dynamic materials to study cell-material interactions in dynamic environments and to aid in the development of functional tissue engineered constructs.

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Open Access

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