GCRIS

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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.
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.
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.

Phd Degree / Doktora

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