Development of peptide based materials as a synthetic scaffold to mimic extracellular matrix

dc.contributor.advisorTekinay, Ayşe Begüm
dc.contributor.authorSever, Melike
dc.departmentGraduate Program in Materials Science and Nanotechnologyen_US
dc.descriptionCataloged from PDF version of article.en_US
dc.descriptionThesis (Ph.D.): Bilkent University, Department of Materials Science and Nanotechnology, İhsan Doğramacı Bilkent University, 2017.en_US
dc.descriptionIncludes bibliographical references (leaves 121-146).en_US
dc.description.abstractBiomaterials obtained through self-assembling process of peptide amphiphile (PA) molecules provide great potential to introduce new therapeutic approaches in regenerative medicine through mimicking the natural environments of different types of tissues. The ability of self-assembled PA nanofibers to mimic natural extracellular matrix (ECM) renders them attractive for regenerative medicine applications. The materials-cell interactions can be modulated through the surface modification of the materials such as introducing the bioactivity via short bioactive peptide sequences derived from natural ECM proteins, which regulate cell behavior through controlling of cellular activities such as proliferation and differentiation. Herein, I described my studies on the development of PA nanofibers in order to mimic natural ECM with differentiation and regeneration purposes. Heparan sulfate mimetic and laminin mimetic PA nanofibers were used as a potential therapeutic approach in Parkinson's disease (PD). These bioactive PA nanofibers were found to reduce the progressive cell loss in SH-SY5Y cells caused by 6-hydroxydopamine treatment in vitro, and improve neurochemical and behavioral consequences of Parkinsonism in rats and provide a promising new strategy for treatment of PD. These nanofibers also proved to be effective in enhancing the viability of Schwann cells and increase nerve growth factor (NGF) release from these cells in vitro. Since NGF has a crucial role in nerve injury repair and myelination in the regenerating nerve, the bioactive epitopes used in this study present also a promising approach as guidance cues for regenerating axons. Tenascin-C is another multifunctional ECM glycoprotein common in both nerve and bone tissue. By decorating peptide nanofibers with tenascin-C derived epitope and using in three-dimensional (3D) system, this tenascin-C mimetic 3D cell culture system was found to provide both the biochemical and physical aspects of the native environment of neural cells, thereby filling the gap between 2D cell culture models and in vivo environments and contributing to more tissue-like structure and more predictive approaches to organogenesis and tissue morphology. Within the scope of this thesis, tenascin-C mimetic nanofibers were also used for osteogenic differentiation of mesenchymal stem cells (MSCs). They were found to significantly enhance the attachment, proliferation, and osteogenic differentiation of MSCs even in the absence of any external bioactive factors and regardless of the suitable stiff mechanical properties normally required for osteogenic differentiation.en_US
dc.description.statementofresponsibilityby Melike Sever.en_US
dc.format.extentxxi, 1476 pages : illustrations, charts (some color) ; 29 cmen_US
dc.publisherBilkent Universityen_US
dc.subjectPeptide nanofibersen_US
dc.subjectExtracellular matrixen_US
dc.subjectParkinson’s diseaseen_US
dc.subjectNeural differentiation and regenerationen_US
dc.subjectOsteogenic differentiationen_US
dc.titleDevelopment of peptide based materials as a synthetic scaffold to mimic extracellular matrixen_US
dc.title.alternativeHücreler arası matrisin taklit edilmesi için sentetik iskele olarak peptit tabanlı malzemelerin geliştirilmesien_US
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