Development of peptide nanomaterials for neural regeneration

buir.advisorTekinay, Ayşe Begüm
dc.contributor.authorMammadov, Büşra
dc.departmentGraduate Program in Materials Science and Nanotechnologyen_US
dc.descriptionCataloged from PDF version of thesis.en_US
dc.descriptionIncludes bibliographical references (leaves 132-148).en_US
dc.descriptionThesis (Ph. D.): Bilkent University, Materials Science and Nanotechnology Program, İhsan Doğramacı Bilkent University, 2015.en_US
dc.description.abstractNervous system consists of a dense network of cells and their connections and exhibits a high level of complexity. This complexity arises from the high variety of cell types with very specific functions, the high number of cells along with the abundance of connections between these cells. When combined with the nonproliferative nature of neural cells and inhibitory nature of the pathological extracellular matrix (ECM), this complexity leads to a very limited regenerative potential. Thus neurodegenerative disorders and traumatic injuries of neural tissues lead to lifelong disabilities due to the poor success of current therapies. Novel therapeutic approaches which can overcome barriers that impede neural regeneration are therefore required to be developed. Smartly designed nanomaterials that can direct cells towards desired functions can improve the regeneration of neural tissues. Herein, I have described my work on development of peptide nanofibers for neuroregeneration and biological applications of these nanomaterials. To achieve the regeneration of the nervous system, the composition of the neural ECM under healthy conditions and during early development was mimicked through structural resemblance and bioactive epitope presentation using nanofibers. Laminin derived IKVAV peptide sequence and glycosaminoglycan mimicking, growth factor-binding sulfonated peptide sequence were presented on peptide nanofiber scaffolds. Differentiation of PC-12 cells, a model cell system for neuroregenerative studies, was found to be improved on these nanofiber scaffolds when compared to the cells on epitope free control scaffolds. Cells could even extend neurites on these scaffolds in the presence of inhibitory chondroitin sulfate proteoglycans. These nanofibers also proved to be efficient in sciatic nerve regeneration after injury. When injected into the lumen of polymeric nerve guidance channels, this bioactive nanofiber system provided guidance to the elongating axons and resulted in better axonal regeneration that was evident both from histological analysis and electromyography results. Results of in vitro and in vivo experiments were correlated and indicated the neuroregenerative potential of these peptide nanofibers. In addition, semiconductive oligothiophene was encapsulated in peptide nanofibers without compromising the biocompatibility. These hybrid nanofiber scaffolds can potentially be used for electrical stimulation of neurons that can further boost regeneration.en_US
dc.description.statementofresponsibilityby Büşra Mammadoven_US
dc.format.extentxiv, 148 leaves : charts.en_US
dc.publisherBilkent Universityen_US
dc.subjectPeptide nanofibersen_US
dc.subjectNeural regenerationen_US
dc.subjectSciatic nerveen_US
dc.titleDevelopment of peptide nanomaterials for neural regenerationen_US
dc.title.alternativeSinirsel rejenerasyon amaçlı peptit nanomalzemelerin geliştirilmesien_US
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