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Development of novel citric-based biomaterials for treatment of diabetes and its complications

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Diabetes mellitus is a metabolic disease characterized by the abnormal high blood glucose of patients. The defects in the hormonal regulation, including impaired insulin secretion, insulin action, or the combination of the two are usually the causes of such a disease. The elevated blood glucose also leads to a wide range of metabolic, microvascular, and macrovascular complications, which have resulted in a sizeable impact on the global burden of morbidity and mortality.', 'In this dissertation, I investigated the application of poly(polyethyleneglycol citrate-co-N-isopropylacrylamide (PPCN), a citric-based, degradable, thermoresponsive, antioxidant material, for developing a targeted treatment plan for the diabetic foot ulcers that is one of the severe type of complications of diabetes mellitus. PPCN undergoes a thermo-reversible transition that does not denature the incorporated angiogenic chemokine and can be readily modified with cell adhesion peptides to stimulate cell proliferation and promote cell ingrowth, it can also be applied over the irregular shaped chronic wound bed, stimulating angiogenesis and native dermal tissue regeneration. ', 'This dissertation also exploited the use of PPCN as a biomaterial scaffold to support the transplantation of islets of Langerhans for the treatment of type I diabetes, or chronic pancreatitis. I have demonstrated that PPCN can protect islet from oxidative stress damage whiling preserving its function both in vitro and in vivo. Long-term euglycemia was achieved in rodents with the marginal number of islets (at a one donor per recipient level). Non-human primate safety test demonstrated a good biocompatibility of PPCN for the great omentum location. These results supported the use of an injectable anti-oxidant scaffold to improve islet isolation yield and islet performance after the transplantation.', 'Lastly, this dissertation laid the groundwork for developing a nanoparticle-based donor specific tolerization therapy for the transplant rejection problem. Made of an amphiphilic block co-polymer poly (ethylene glycol)-bl-poly(propylene sulfide) (PEG17-bl-PPS30), the bilayer polymersome nanoparticles can deliver both hydrophobic and hydrophilic donor antigens in a spleen and liver-targeted manner.

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  • 10/21/2019
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