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Development of glucose releasing biomaterials for applications in cell therapies

Rizzo, Sebastiano 2023. Development of glucose releasing biomaterials for applications in cell therapies. PhD Thesis, Cardiff University.
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Cell therapies hold the potential to halt or reverse several pathologies, including Parkinson’s Disease. Despite showing promise, cell death post transplantation remains a limitation and recent findings have suggested that a paucity of glucose is playing a crucial role in graft death. To improve graft survival, this work aimed to formulate glucose releasing materials, which can sustain cell metabolism during hypoxic period, when cells are facing a condition of oxygen-glucose deprivation (OGD). To assay the glucose released from the various formulations tested, an enzymatic assay based on glucose oxidase/horseradish peroxidase tandem reaction was optimised for glucose detection in the 0.2-2 mg/mL range, relevant to cell culture techniques. By encapsulating glucose into a variety of photocrosslinkable acrylate-containing monomers, it was possible to produce macroscale version (1.5 x 2.0 mm) of the glucose releasing materials. These materials allowed for an easy screening of several formulations, which were used to understand the principles underlaying glucose release and how to obtain sustained glucose delivery. Although it was possible to formulate injectable version of these materials, the glucose release rate from the microparticles was mostly brief and inadequate to the time course required. Nonetheless, one of the formulations suggested that sustained glucose release could be obtained also from microparticles. To mimic the prolonged graft ischemia, and assess glucose impact on hypoxic neurons, iPSCs derived neurons (dopaminergic, medium spiny and cortical), foetal ventral mesencephalon tissue and SH-SY5Y cells were cultured up to 96 hours either at 21% or 0.1% pO2 at different glucose concentrations. iv This work shows that: 1) glucose paucity, rather than oxygen deprivation, negatively affects neurons viability; 2) glucose can be released in a sustained manner (7-16 days) and, although showing a brief release, 3) in vitro, the microparticles were able to rescue cell viability from OGD-induced death.

Item Type: Thesis (PhD)
Date Type: Completion
Status: Unpublished
Schools: Pharmacy
Subjects: Q Science > Q Science (General)
Date of First Compliant Deposit: 19 June 2023
Last Modified: 19 Jun 2023 08:55

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