Molecular analysis of enginereed nanomaterials in biomedical and regenerative medicine applications
Author(s)
Advisor
Elbüken, ÇağlarDate
2019-04Publisher
Bilkent University
Language
English
Type
ThesisItem Usage Stats
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Abstract
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.
Keywords
Nanoparticle; toxicityCell-nanomaterial interactions
Gold nanoparticles; nanoparticle accumulation
Organoid
HMGCS2
Beta hydroxybutyrate
Small intestine
Oral ketone delivery
Mineralization
Enamel
Self-assembling peptide