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Phototunable Click-based Hydrogels for 3D Cell
Culture: Dynamic Tailorability of the Stem Cell Niche
A growing concept in organic synthesis is the
development of extremely selective and orthogonal
reactions that proceed with high efficiency and under a
variety of mild conditions.
The goal is to develop independently modular
reactions that enable the facile synthesis of functional
molecules, and ultimately materials with highly defined
properties.
Such reactions have been grouped under the term “click
chemistry,” with the most common example being the
copper(I)-catalyzed reaction of azides with alkynes to
form triazoles.
While the versatility of click reactions has been
broadly exploited, a major limitation, especially in
natural systems, is the intrinsic toxicity of the
synthetic schemes and the inability to translate these
approaches to biological applications.
My project seeks to develop synthetic strategies
where macromolecular precursors react via a copper-free
click chemistry, allowing for the direct encapsulation
of cells within click hydrogels.
Gels formed via this step-growth polymerization
mechanism have minimal local material heterogeneities,
thereby presenting encapsulated cells with an
initially-uniform mechanical environment.
Subsequently, an orthogonal thiol-ene
photocoupling chemistry enables patterning of biological
functionalities within the gel in real-time and with
micron-scale resolution, allowing one to tailor the
physical and chemical properties of the cell culture
niche in situ.
These local manipulations of the gel
microenvironment provide an avenue to introduce chemical
cues that direct cell function (such as migration,
proliferation, or differentiation) and/or assay cell
behavior (viability, metabolic activity, or motility)
throughout specific regions of interest within the
material.
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