Phd Degree / Doktora

Permanent URI for this collectionhttps://hdl.handle.net/11147/2869

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Access type: Open accessAuthor: search.filters.author.Özçivici, Engin

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  • Doctoral Thesis
    Magnetic Manipulation of Cells for Tissue Engineering and Diagnostic Applications
    (01. Izmir Institute of Technology, 2025) Özkan, İlayda; Özçivici, Engin
    Bu tez kapsamında, negatif magnetoferez prensibine dayalı manyetik levitasyon tekniği, iki farklı yaklaşım için kullanılmıştır. İlk olarak, manyetik levitasyon sistemi, doku iskelesiz üç boyutlu doku modelleri oluşturmak için bir biyofabrikasyon yöntemi olarak kullanılmıştır. İlk yaklaşımda, in vivo dokuyu daha iyi taklit edebilen, üç boyutlu heterojen küresel modeller geliştirmek ve iyileştirmek amaçlanmıştır. Tek halka mıknatıs tabanlı levitasyon sisteminde çeşitli konfigürasyonlarda heterojen meme kanseri küreleri elde edilmiştir. İki farklı hücre tipinin lokalizasyonunda sferoid yapı içerisindeki farklı hücre yükleme parametrelerinin etkisi incelenmiştir. Ek olarak, hücre dışı matriks birikimini artırarak, manyetik levitasyon ile oluşturulan doku iskelesiz sferoid modellerin in vivo yapıyı taklit edebilme kapasitesini artırmak için makromoleküler kalabalıklaştırma yöntemi entegre edilmiştir. İkinci olarak, nörogelişimsel bozukluklarda teşhis amaçlı olarak manyetik levitasyonun kullanımı araştırılmıştır. Araştırmada, sağlıklı bireylerden ve nörogelişimsel bozukluğu olan bireylerden elde edilen fibroblastlar, sinir progenitör hücreleri ve indüklenmiş pluripotent kök hücreler arasındaki farkı belirlemek amacıyla hücrelerin özkütle profilleri analiz edilmiştir. Ayrıca, farklı tipte lizozomal depo hastalıklarının hücre özkütlesi üzerindeki etkisi fare modellerinden izole edilen primer nöroglial hücreler kullanılarak incelenmiştir. Bu tezde, hem doku mühendisliği uygulamaları hem de hücre bazlı tanı çalışmalarında hızlı, maliyet etkin ve güvenli bir yöntem olarak manyetik levitasyon tekniğinin potansiyeli gösterilmiştir.
  • Doctoral Thesis
    Magnetic Levitation of Cells From Bone Marrow Origin
    (Izmir Institute of Technology, 2021) Anıl İnevi, Müge; Özçivici, Engin; Güven, Sinan
    Magnetic levitation via negative magnetophoresis is a new label-free technology that is important in cell- and tissue-level bioengineering applications. Biofabrication applications of the technology is an area that still needs to be developed. In this doctoral thesis, 3D cellular structures with contrable size and cellular arrangement were formed and cultured with magnetic levitation using bone marrow-derived stem cells in both a miniature system that provides levitation between two magnets and a ring magnet-based large-scale system. First, a miniaturized magnetic levitation system that allows real-time imaging was produced and comprehensive protocols were described for its use for both single-cell level analysis and cell culture. With this setup, complex in situ 3D cellular aggregates were formed and their culture was maintained by levitation. Then, a new system that provides levitation on a single ring magnet was produced and used for biofabrication for the first time to overcome the reservoir volume constraint in the existing system and thus to create larger and symmetrical 3D cellular clusters. With the elimination of the upper limit in the system, the volume of the chamber was increased and the medium and biological structure transfer became easily applicable. It has been shown that this ring magnet-based magnetic levitation setup is suitable for cell culture, formation of millimeter-sized cellular structures with various cell types, and that pre- formed cellular structures can be combined by levitation. The low-cost and easy-to-use systems presented in this thesis have the potential to be applied in many areas such as tissue engineering and drug testing.
  • Doctoral Thesis
    Molecular and Cellular Level Adaptations of Bone Marrow Mesenchymal Progenitor Cells To Chemical and Physical Signals
    (Izmir Institute of Technology, 2020) Baskan Erbilgiç, Öznur; Özçivici, Engin; Atabey, Safiye Neşe
    Mechanical forces are the integral determinants in cell and tissue homeostasis and regeneration, and they can affect numerous biological process from proliferation to fate determination. Mechanical forces that possess low magnitude and high frequency characteristics are also known as low intensity vibrations (LIVs). These signals were studied widely on many cell types for regenerative purposes, however most of these studies select components of LIV signals (e.g. magnitude, frequency, duration, etc.) arbitrarily. Here, we addressed the effect of LIV applied frequency, LIV daily exposure time and fate induction on the viability of preadipocyte 3T3-L1 cells. For this, we performed a frequency sweep that was ranging from 30 to 120 Hz with 15 Hz increments applied for 5, 10 or 20 minutes during quiescent growth or adipogenesis for up to 10 days. Results suggest that the applied frequency and fate induction was an important determinant of cell viability, lipid droplet physiology, triglyceride concentration, cell density and adipogenic-specific gene expression while daily exposure time had no effect. These findings contribute to the effort of optimizing a relevant mechanical stimulus that can inhibit adipogenesis. On the other hand, random and aligned PAN/PPy nanofibers were investigated as a scaffold material for osteogenic differentiation of D1 ORL UVA mouse bone marrow mesenchymal stem cells. Cells were able to attach and grow on nanofibers confirmed by cell viability results. Stem cells that were cultured with osteogenic induction were able to mineralize on electrospun nanofibers based on alizarin red and Von Kossa dye staining. For aligned PPy nanofibers, mineralization occurred in the fiber alignment direction. Consequently, PAN/PPy nanofibrous mats in both random and aligned forms would be potential candidates for bone tissue engineering.
  • Doctoral Thesis
    Biochemical and Mechanical Cues for Osteogenic Induction of Stem Cells on Paper Based Scaffolds
    (Izmir Institute of Technology, 2019) Karadaş, Özge; Özçivici, Engin; Özhan Baykan, Hatice Güneş
    Tissue engineering aims to produce functional constructs with living cells that can fully integrate with the tissue when inserted into the body. Design of the scaffold and the choice of cell type that will be used for production of the tissue engineering construct are very important for the success of the application. For bone tissue engineering, incorporation of substances with antimicrobial properties can supply additional benefits. This dissertation seeks answers for two discrete questions in different chapters: Do carnosol and carnosic acid, phenolic antimicrobial compounds extracted from plants have cytotoxic effect on bone tissue derived cells and do the culture conditions (monolayer or 3D) effect the response of cells (Chapter 2); and how do application of a single type of mechanical force (vibration) and a combination of two forces (vibration plus fluid shear) affect the osteogenesis of tissue engineering constructs (Chapters 3 and 4)? The results of this research demonstrated that carnosol and carnosic acid had bacteriostatic effect at 60 µg/mL but this concentration value was highly cytotoxic for bone tissue derived cells. Nevertheless, when the same cells were incubated under 3D culture conditions their cytotoxic tolerance was higher. The supportive role of mechanical forces on osteogenic differentiation of stem cells on 3D scaffolds prepared by using filter paper, on the other hand, was demonstrated with the increase in osteoblastic gene expression, immunocytochemical staining and detection of mineralization by Alizarin red S staining and quantification. In conclusion this research showed the importance of biochemical and biomechanical cues on osteogenesis.
  • Doctoral Thesis
    Invetigation of Mechanical Vibration Effects on Breast Cancer Cells
    (Izmir Institute of Technology, 2018) Olçum Uzan, Melis; Özçivici, Engin; Erdal Bağrıyanık, Şerife Esra
    In this doctoral dissertation, low magnitude mechanical signals (LMMS, <1g in magnitude) were used to test the stress shielding model hypothesized on breast cancer cells. The hypothesis was that the breast cancer cells will be sensitive to mechanical vibrations and will respond to these vibrations. It was similarly used to test the adipogenic differentiation of Lamin A/C knockdown (by siRNA) bone marrow-derived mesenchymal stem cells. It is known that Lamin A/C plays a role in the nucleus and intracellular organization in these cells and affects gene expression by chromatin regulation. The hypothesis was that if these cells are deprived of the organization for the nucleus, they will be sensitive to mechanical vibrations, but that the mechanical vibrations cannot restore the effect of lamin A/C on gene regulation. We investigated the effects of high-frequency low-density mechanical signals (LMMS) on cell proliferation, apoptosis, cell cycle, protein expression, differentiation, cytoskeleton and phenotypic change processes. According to findings, LMMS caused cell cycle arrest in the aggressive type of breast cancer cells and slowed proliferation. Non-aggressive breast cancer has not responded to LMMS. In mammary epithelial cells, LMMS has not shown an effect that triggers proliferation. In the mesenchymal stem cell model, Lamin A/C knockdown accelerated adipogenic differentiation. Although LMMS in these cells decreased the rate of adipogenic differentiation, it was not sufficient to restore the baseline.