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Chemically tunable biocompatible hydrogels as a novel approach to combatting disease
Mann, Katie
Mann, Katie
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2024-12
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Abstract
Macrophages are immune cells that play diverse roles, from killing invading pathogens to coordinating the wound healing process. Unlike many cell types, macrophages are 'plastic', able to transition from their ‘killing’ role to their 'rebuilding' role in response to chemical cues. Remarkably, emerging evidence has shown that macrophage plasticity can also be activated in response to mechanical signals. In general, stiff environments promote a killing phenotype, while softer environments promote a wound-healing phenotype. We aim to design a biocompatible, chemically responsive implantable hydrogel which would provide a means to influence macrophage phenotype via mechanical cues. This material would present a novel approach to combatting complex diseases such as cancer. Polyethylene glycol (PEG) hydrogel matrices are promising springboards for designing implantable materials due to their established biocompatibility and chemical versatility. To implement controllable mechanical properties into the PEG hydrogel, we utilize dynamic covalent hydrazone/oxime bonds as the crosslinking bonds between the polymers of the material. We will form the tunable hydrogel matrix from the appropriately functionalized 4-Arm PEG molecules. We will then use rheology to quantify the viscoelastic behavior of the hydrogel to confirm that it exhibits the desired mechanical dynamics. In particular, we anticipate that the material will exhibit rapid dynamics and thus remain more fluid/soft under physiological pH. Conversely, we hypothesize that the hydrogel will undergo oxidation upon exposure to inflammatory oxidative metabolites (e.g., those generated by tumor cells), causing the material to rapidly stiffen. Finally, we will analyze the efficacy of our hydrogel in triggering the transition of the macrophages from the ‘healing’ to the ‘killing’ phenotype by performing macrophage studies under varying mechanical conditions of the tunable hydrogel. Successful design of this manipulable hydrogel would identify a novel way of reprogramming the immune system to combat disease using mechanical cues.
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Creative Commons CC-BY License or the Creative Commons CC-BY-NC License.
Copyright of the original work is retained by the author.
Copyright of the original work is retained by the author.