Graduate Thesis Or Dissertation

 

Fundamental Characterization of Photodegradable Hydrogels: Spatiotemporal Control of the Cellular Microenvironment Public Deposited

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https://scholar.colorado.edu/concern/graduate_thesis_or_dissertations/q811kj78n
Abstract
  • Synthetic hydrogels are an attractive class of materials for the design of well-defined cell culture platforms to better understand how cells receive and integrate signals present in the extracellular environment. Within this class, responsive hydrogels have emerged to investigate questions as to how cells sense and respond to dynamic changes in the mechanical and biochemical nature of the cell niche. To complement this growing body of research, this thesis aimed to develop photoresponsive, synthetic hydrogels that enable experimenters to explore how spatiotemporally varying cues from the extracellular matric influence biological function in real time. Specifically, cytocompatible, chain and step polymerized hydrogels were fabricated from a photolabile, divinyl poly(ethylene glycol) monomer that enable user-defined modulation of gel properties with light in the presence of mammalian cells. A fundamental and quantifiable characterization of how light-induced property changes alter the structure and function of these photodegradable hydrogels was conducted through experimental and modeling approaches. Similarly, the chemically similar chain and step polymerized hydrogels were employed to better understand how network connectivity affects mechanical integrity and degradation in water-swollen polymer networks. Based on this thorough characterization of how light can be exploited to modulate the structure of photodegradable hydrogels, several experiments were conducted to study how dynamic alterations in the mechanics and biochemistry of the extracellular matrix influence and direct specific cell function. For this, cytocompatible gelation and irradiation conditions that enable light-induced material property changes in the presence of cells were determined. Gradients in gel density were photopatterned into three-dimensional hydrogels to explore how encapsulated cells respond to changes in the elasticity of the surrounding environment, while micron-scale regions of two-dimensional hydrogels were photoeroded to disrupt cell-material interactions on the subcellular length scale, inducing dynamic cell retraction. Photodegradable hydrogels were further processed into protein-laden microspheres to enable the spatially and temporally defined release of bioactive factors to cells during culture. Finally, unique photodegradable materials were engineered based on the principles developed in this thesis that enable the selective culture or capture of mammalian cells that can subsequently be liberated or released from the hydrogel material. Collectively, this thesis research developed a fundamental understanding of light-induced structure and function changes in photodegradable, poly(ethylene glycol) hydrogels through experimental characterization and modeling. This knowledge was then applied to modulate both the physical and chemical nature of the cellular microenvironment in real time and in the presence of cells with spatial and temporal control. The ability to modulate gel properties in a defined and predictable manner enabled unique studies of how cellular function is related to dynamic signals from the extracellular matrix. This approach and characterization should prove useful for those seeking to investigate complex biological questions that depend on dynamic signaling from the extracellular microenvironment and should further the development of responsive materials that enable precise and predictable user-defined changes in structure and function.
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  • 2012
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  • 2019-11-14
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