Dynamic photo-tunable hydrogels for temporal modulation of matrix mechanical properties




Stowers, Ryan Scott

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The extracellular matrix is highly influential in regulating cell fate and function in vivo. Biophysical cues from the microenvironment are involved in nearly every cellular phenomenon, from initial embryogenesis to diseases such as atherosclerosis and cancer. This dissertation seeks to develop 3D hydrogel models to more accurately recapitulate the in vivo microenvironment by allowing for temporal modulation of stiffness. A strategy is presented to spatially and temporally tune the mechanical properties of 3D alginate-based hydrogels using a light-triggered mechanism. This approach is demonstrated to be cytocompatible and highly tunable. The system is employed to elucidate the morphological response of fibroblasts to stiffening 3D environments. Additionally, the platform is translated to an in vivo application of transdermal gel modulation. Finally, the phototunable hydrogels are used to evaluate the effect of matrix stiffening on breast epithelial cells in a mechanical environment that mimics tumor stiffening. Changes in the mechanical properties of the gel induce phenotypic changes to MCF10A epithelial cells, including collective cell migration from the mammary acini. This system is broadly applicable to the biomaterials community and could shed light on a number of outstanding biological questions.


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