Phd Degree / Doktora

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

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Department: search.filters.department.Thesis (Doctoral)--İzmir Institute of Technology, BioengineeringSubject: search.filters.subject.Tissue engineering

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Now showing 1 - 4 of 4
  • Doctoral Thesis
    Xylan Based Composite Nanoparticles and Biofoams for Drug Delivery and Tissue Engineering
    (01. Izmir Institute of Technology, 2022) Zeybek, Nüket; Büyükkileci, Ali Oğuz
    Xylan is a hemicellulosic polysaccharide, which can be obtained from forest and agricultural wastes. Similar to some other polysaccharides, xylan can find application in drug delivery and tissue engineering due to its availability, structural diversity, biocompatibility, biodegradability, and low cost. In the first part of the study, xylan-based nanoparticles were developed for colontargeted oral drug delivery. Xylan is resistant to digestion and absorption in the upper GIT and is degraded by hydrolysis of glycosidic bonds by the colon microbiota; this makes it prominent in targeted drug delivery to the colon. The drug carrier was combined with a polymeric micelles system to increase the bioavailability of hydrophobic bioactive molecules in the colon targeting. The model hydrophobic molecule, curcumin, was loaded in the core of the triblock copolymer P-123 micelles by the thin-film hydration method. Curcumin-loaded micelles were coated with xylan supported by chitosan and tripolyphosphate using the ionic gelation method. In another approach, xylan was also used to coat curcumin-loaded mesoporous silica nanoparticles to prevent premature drug release in the upper GIT in colon-targeted delivery. In both approaches, the drugcontaining structures were maintained up to the colon and the drug was released upon bacterial hydrolysis of xylan. In the second part, xylan-based biofoams were synthesized by the oil in water emulsion templated method. Several physicochemical and mechanical tests have shown that at the optimal conditions foams with promising properties could be synthesized. Besides, to develop a more effective tissue therapy by utilizing the synergistic effect of the drug delivery and scaffold system, a model drug was successfully loaded into biofoams. This study showed that xylan is a promising feedstock for the synthesis of stable and biocompatible materials in biomedical applications, which reveals its potential capability in drug carriers and scaffolds.
  • Doctoral Thesis
    Engineering Target Tissue in Lab-On Devices for Predicting Homing Choices of Metastatic Cancer
    (Izmir Institute of Technology, 2020) Batı Ayaz, Gizem; Pesen Okvur, Devrim; Yavuz, Oktay
    The metastatic cascade of cancer results in the extravasation of the tumor to other parts of the body. Metastasis is the leading cause of cancer related deaths. Breast cancer is the most common cancer in women, and lung is one of the organs with the most metastasis. For this reason, it is critical to engineer a tissue microenvironment that includes complex cell-cell interactions with co-culture of endothelial, epithelial and stromal cells, and the invasion and extravasation steps of metastasis can be observed for early diagnosis of metastasis. Vascularization is the critical step for engineering the tissues. The in vitro models used today are insufficient to create the tissue environment closest to in vivo conditions. Recently developed lab-on-a-chip platforms provide suitable environments for mimicking the in vivo structure in tissue engineering studies. In this research: -Different lab-on-a-chip devices fabricated to engineer breast and lung target tissues. -For the first time, epithelial, fibroblast and endothelial cells were tri-cultured and breast and lung tissue environments were engineering with microvasculature. -Different gel, media and cell numbers have been optimized for engineering of breast and lung tissue environments with microvascularization. -Different matrix environments have been optimized to observe invasion and/or extravasation steps separately or together.
  • 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
    Preparation and Characterization of Polymeric Scaffolds for Nerve Tissue Engineering Applications
    (Izmir Institute of Technology, 2014) Büyüköz, Melda; Alsoy Altınkaya, Sacide; Erdal, Şerife Esra
    The major goal in tissue engineering is to develop three-dimensional biomimetic scaffolds which can provide an optimal environment for cell adhesion, proliferation, differentiation and guide new tissue formation. In this study macroporous, nanofibrous gelatin scaffolds in the form of a disc and channeled conduit were prepared for nerve tissue engineering applications. Alginate microspheres have been integrated into the scaffolds to deliver nerve growth factor (NGF) to differentiate PC12 cells. Methods combining thermally induced phase separation technique with porogen leaching and injection molding were used to manifacture disc shaped and channeled nanofibrous scaffolds, respectively. Microcarriers loaded with NGF were fabricated by water-in-oil emulsification technique and attached in the scaffold by chemical crosslinking with carbodiimide reaction. The relationship among processing parameter, porosity, pore size, interpore connectivity and the mechanical properties were investigated. In addition release kinetics of NGF from the particles were determined and viability, proliferation and differentiation of PC12 cells in the scaffolds were evaluated. The fiber sizes of nanofibrous scaffolds were found similar to the size of natural collagen fiber bundles. In nanofibrous scaffolds, the dimensional stability and in vitro degredation rates improved when compared to solid walled scaffolds. The release rate of NGF from the particles was controlled by the alginate concentration and poly(L-lysine) coating. Integrating NGF into the nanofibrous gelatin scaffold in encapsulated form reduced amount of NGF and time required for the differentiation of PC12 compared to free NGF directly added to the cells.