Things Fall Apart: Designing Materials that Break Down with Specific Chemical Agents

PROJECT NUMBER: 27

AUTHOR: Cameron Fitzgerald, Chemical and Biological Engineering

MENTOR: Dylan Domaille, Chemistry | MENTOR: Gun Su Han, Chemistry

ABSTRACT

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The kidneys filter and remove waste, minerals, and fluid from the body by producing urine. Kidney transplantation is the most common transplant procedure, and it is used to replace a failing kidney with a healthy one. Because kidneys play a vital role in the human body, clinicians closely monitor the transplant health post-surgery. Current diagnostic methods including Doppler ultrasonography, renal scintigraphy, and fine-needle aspiration (FNA) biopsy have proven to be useful diagnostic tools yet remain invasive and expensive. To address these problems, we are developing injectable hydrogels that release a fluorescent “flare” in response to transplant rejection. In this design, the fluorescent flare is simultaneously activated and released upon increases in reactive oxygen species (ROS), the concentration of which rise when the immune system attacks the transplant. The fluorescent molecule is secreted in the patient’s urine, which provides a non-invasive signal to the patient that their transplant is undergoing stress.
Dynamic crosslinked hydrogel networks are a key component of our design. These bonds have the ability to break and reform, allowing the gel to display injectability and reassembly due to the presence and absence of a shear force, respectively. With the inclusion of crosslinks that degrade in the presence of ROS, hydrogel networks also degrade in the presence of oxidative stress. Here, we present 3´,6´-bis(pinacolatoboron)fluoran (PeroxyFluor-1, PF-1) a boron-functionalized fluorescein molecule that is attached to the hydrogel and serves as the essential signaling component of our solution. In this design, the molecule is simultaneously non-fluorescent and crosslinks the hydrogel. Upon exposure to ROS, the oxidation of PF-1 simultaneously removes it from the hydrogel and makes it fluorescent, where it is subsequently secreted in the patient’s urine.
To date, we have accomplished the synthesis of PF-1 and are currently exploring its ability to simultaneously crosslink a hydrogel while also retaining its ability to become fluorescent in the presence of reactive oxygen species (ROS). Our future efforts are focused on tuning the reactivity of the signaling molecule to various ROS and determining the most effective means by which to attach the signaling molecule to the hydrogel.

VISUAL PRESENTATION

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AUTHOR BIOGRAPHY

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Cameron Fitzgerald is a Junior at the Colorado School of Mines. He is majoring in chemical engineering and minoring in data science. Cameron is currently working with the Domaille laboratory, in the Chemistry Department, to develop patient-monitored hydrogels to detect organ transplant rejection.

Sponsored by Phillips 66