Molecular Analysıs of Engınereed Nanomaterıals in Bıomedıcal and Regeneratıve Medıcıne Applıcatıons
Molecular mechanisms are inspiration source for effective nanomaterial synthesis through minimalist bottom-up approaches. Mimicking functional bio-physicochemical properties of biomacromolecules can give new insights for design and synthesis of nanomaterials used in biomedical and regenerative medicine applications.
In this thesis, I describe two different biomedical applications of engineered nanomaterials (ENMs) and potential toxicity of ENMs in long-term exposure at cellular level. First application is oral ketone delivery to intestine: Lack of ketone body betahydroxybutryrate (βOHB) generated by a metabolic enzyme, hydroxymethylglutaryl CoA synthase 2 (HMGCS2), compromises intestinal stem cell maintenance in intestine and intestinal regeneration capacity after radiation injury. PLGA-encapsulated and oligomer forms of βOHB are used to rectify consequences of βOHB depletion in intestine. Second application is amelogenin-mimicking self-assembling peptides driven mineralization in eroded enamel. These are just two examples of ENMs in biomedical and regenerative medicine applications. Increasing number of ENMs bring an issue with self: nanotoxicity and safety. In this thesis, I also describe a novel long-term nanoparticle accumulation model to understand active regulation of nanoparticle uptake, nanoparticle accumulation behavior and the impact of long-term exposure on cellular machineries. Overall these studies show potential of engineered nanomaterials in vast range of biomedical and regenerative medicine applications and their long-term toxicity in organisms at a cellular level.