Molecular analysis of enginereed nanomaterials in biomedical and regenerative medicine applications

Molecular mechanisms are inspiration source for effective nanomaterial synthesis through minimalist bottom-up approaches. Mimicking functional biophysicochemical properties of biomacromolecules can give new insights for design and synthesis of nanomaterials used in biomedical and regenerative medicine applications. In this thesis, rationally-designed nanomaterials and their biomedical applications as oral ketone delivery and biomineralization and long-term potential toxicities were investigated. In the first chapter, basic concepts of nanomaterial design, synthesis, characterization, and nano-bio interface were explained. In the second chapter, a novel long-term nanoparticle accumulation model was developed to understand active regulation of nanoparticle uptake, nanoparticle accumulation behavior and the impact of long-term exposure on cellular machineries (e.g. ER stress). In the third chapter, the role of ketone body betahydroxybutryrate (βOHB) generated by a metabolic enzyme, hydroxymethylglutaryl CoA synthase 2 (HMGCS2), on intestinal stem cell maintenance and regeneration after radiation injury was investigated. Consequences of βOHB depletion in intestine were rectified by oral delivery of PLGA-encapsulated and oligomer forms of βOHB. The last chapter, acidic epitopes of enamel proteins (e.g. amelogenin) were integrated into self-assembling peptides to remineralize eroded enamel. Overall these studies show potential of natureinspired engineered nanomaterials in vast range of biomedical and regenerative medicine applications.