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Date of Award
Master of Science (MS)
Ischemic diseases, including myocardial infarction, stroke and limb ischemia, are life-threatening vascular diseases with high mortality. Under ischemic condition, less blood supply causes insufficient oxygen and nutrients transported to the affected tissues, which leads to cell death. To support cell survival under ischemia, oxygen and nutrients (especially glucose) are needed for aerobic respiration to generate energy. Therefore, directly supplying oxygen and glucose to the ischemic tissues is a promising therapy for ischemic diseases. In this work, we aim to design biomaterials to deliver oxygen and glucose to enhance cell survival under ischemia. In the first project, we fabricated oxygen releasing nanoparticles with Polyvinylpyrrolidone peroxide complex encapsuled in a pH-responsive polymer shell. The polymer shell had a Schiff base structure that serves as crosslinks at pH=7.4, and will decrosslink at pH=6, leading to adjustable oxygen release in response to the environment. We find that the oxygen release rate was faster at low pH, and slower at high pH. With oxygen releasing nanoparticles, cell survival was significantly enhanced after incubation under hypoxia. We also confirmed that the nanoparticles were stable at physiological condition and non-toxic to cells. In the second project, we fabricated pH-responsive glucose releasing microspheres. Boronic acid group was introduced to the polymer chain, which can grab glucose at high pH and release it at low pH. We find the glucose releasing microspheres have a burst glucose release at pH=6.0, and low release rate at pH=7.4. In the future, we will verify whether the released glucose can stimulate the cellular metabolism and increase cell survival under ischemic condition.
Jessica Wagenseil; Jie Shen
Available for download on Wednesday, April 26, 2023