Phd Degree / Doktora
Permanent URI for this collectionhttps://hdl.handle.net/11147/2869
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Doctoral Thesis Development of Computational Models To Predict the Toxicity of Advanced Materials(01. Izmir Institute of Technology, 2023) Bilgi, Eyüp; Karakuş, Ceyda Öksel; Bedir, ErdalThe aim of this study is to harness computational power to enhance existing knowledge on NM safety and to optimize the use of existing nanotoxicity data. The primary goal is to support the safe(r)-by-design concept, necessitating early integration of safety considerations into NM design through structural manipulation strategies. This thesis focuses on three case studies: zinc oxide, silver, and gold NP, using data manually collected from the literature. Analyses with zinc oxide and silver NP revealed a correlation between their toxicity and both internal (intrinsic properties, size, shape, surface charge) and external (cell and analysis-related properties) factors. For zinc oxide, it was found that coating had significant influence on cell viability, with a critical threshold identified at 20 µg/ml concentration and 10 nm size. Similarly, for silver NPs, concentration, size, and exposure time were significant factors. Coating with organic macromolecules increased cell viability, whereas green-synthesized NPs (using bacteria, plant extracts, algae) decreased it. The gold NP study highlighted that ensemble methods were more effective in elucidating complex relationships, with cellular uptake linked to particle size, zeta potential, concentration, and exposure time. Overall, this thesis contributes to safer-by-design strategies, crucial for developing commercially viable and safe NMs. The findings advocate for a broader toxicity evaluation approach, considering various physicochemical aspects and experimental procedures. The complex interactions observed suggest that advanced algorithms are necessary for accurate modeling, supporting the optimization of experimental parameters in NP engineering for biomedical applications.Doctoral Thesis Investigation of Hemostatic Biomaterials Containing Plant Extracts(Izmir Institute of Technology, 2014) Uslu, Mehmet Emin; Bayraktar, Oğuz; Başal Bayraktar, Güldemet; Akhisaroğlu, MustafaHaemostasis in other words a process which causes bleeding to stop is very important in injury. Recent researches were focused on discovery of haemostatic agents and developing biomaterials which transfer them to the injury side. Therefore plant extracts and three dimensional biomaterials were widely investigated. In this research the extract of Equisetum arvense was investigated as a coagulatory agent. Silk fibroin-hyaluronic acid mixture was used for the preparation of three dimensional sponge like biomaterials. The prepared sponge forms could also be used as scaffold for wound healing. In this research effect of extraction parameters on extract composition and bioactivity was investigated. Effect of extraction parameters were analyzed on 6 factors at 3 levels. It was seen that extraction parameters had high influence on both composition and bioactivity of the prepared extract. Although it was reported that the extract of equisetum arvense had anticoagulant activity, in this research it was shown that changing parameters caused variation of extract bioactivity from anticoagulant to coagulant as a result of changing extract composition. Addition of extract into silk fibroin-hyaluronic acid mixture caused proteins to precipitate as a result of interaction between protein and phenolic compounds. As a result of this precipitation significant decrease in the mechanical strength of biomaterial was observed. In order to minimize this interaction, plant extract was added into the silk fibroin after mixing with hyaluronic acid solution. As a result, mechanical strength and pore size of the biomaterial were increased and pore distribution became more regular. Also biomaterial gained tubular network on both vertical and horizontal dimensions. This would help the proliferation and migration of the fibroblast cells and moreover prevent the formation of scar tissue.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 EsraThe 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.