Master Degree / Yüksek Lisans Tezleri
Permanent URI for this collectionhttps://hdl.handle.net/11147/3008
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Master Thesis Development of 3d Tumor Models for Investigating Drug Efficacy of Sapogenol Derivatives(01. Izmir Institute of Technology, 2024) Pişirici, Necmettin Arda; Yıldız, Ahu ArslanSon dönemin hastalığı olan kanser tedavisi çalışmalarında potansiyel ilaçların etkinliklerinin araştırılması için doku fizyolojisine yüksek benzerlik gösteren 3 boyutlu (3B) hücre kültürü modelleri dikkat çekmektedir. Bu modeller 2B hücre kültürü çalışmalarındaki birçok problemin aşılmasını sağlayarak ilaç geliştirme çalışmalarında tercih edilmektedir. Bu çalışmada yeni nesil manyetik levitasyon (MagLev) kullanılarak üretilmiş 3B tümör sferoid modelleri üzerinde sapogenol türevi potansiyel kanser ilaçları ve FDA onaylı antikanser ilacı Paklitaksel'in (Ptx) ilaç aktivite taramaları yapılmıştır. Manyetik levitasyon yöntemi doku iskelesinden bağımsız olup, iki mıknatıs tarafından yaratılmış manyetik alan içerisinde paramanyetik ajanların etkisiyle manyetize edilmiş hücrelerin yoğunlarına bağlı olarak kendilerine has bir yükseklikte (levitasyon yüksekliği) harici bir kuvvet gerektirmeden asılı kalmalarını sağlamaktadır. Bu yöntemle, levitasyon yükseklikleri aynı seviyede olan hücreler arası etkileşimler artarak 3B sferoid yapıları doku iskelesine ihtiyaç duyulmadan hızlıca elde edilebilmektedir. Tamamlanan çalışmada; tümör sferoid modelleri her hücre hattı için ayrı şekilde elde edilmiştir. MagLev yöntemine ek, kontrol amaçlı, aynı hücre hatlarıyla asılı damlacık yöntemi kullanılarak 3B sferoid modelleri elde edilmiştir. Oluşturulan sferoid modelleri üzerinde 2B hücre kültüründe ilaç etkinliği belirlenmiş sapogenol türevi ilaç moleküllerinin ve Ptx'in aktivitesi araştırılmıştır. Sferoid modelleri üzerinde beklenen toksik etki görülmüş, karşılaştırmalı sonuçlar paylaşılmıştır. Bu sonuçlarla birlikte, 2B hücre kültürü kullanılarak yapılan tümör fizyolojisi araştırmaları yerine bu modellerin dezavantajlarını geride bırakan, gerçek tümör fizyolojisini çok daha yakın seviyede taklit edebilen, klinik araştırmalar öncesinde ilaç taramalarında ve farklı moleküllerin etkilerinin araştırılmışında kolay, gerçekçi ve hızlı sonuçlar sağlayabilecek manyetik levitasyon temelli yeni bir ilaç aktivite tarama modeli geliştirilmiştirMaster Thesis Development and Characterization of Surface-Modified Emulsion Templated Scaffolds for Tissue Engineering Applications(01. Izmir Institute of Technology, 2024) Kocagöz, Mehmet; Dikici, Betül Aldemir; Zareıe, Esma Volga BulmuşEmülsiyon şablonlama, yüksek ve açık gözeneklilik sağlayan avantajlı bir iskele üretim yöntemidir. Bu yöntemde hidrofobik polimerlerin su ile karıştırılmasıyla yağ içerisinde su (w/o) emülsiyonları elde edilir. İç faz hacmi %74'ün üzerinde olan polimerize emülsiyonlar, yüksek iç fazlı emülsiyonlar (PolyHIPE'ler) olarak adlandırılır. Polikaprolakton, doku mühendisliğinde yaygın olarak kullanılan sentetik, biyolojik olarak bozunabilen ve biyouyumlu bir polimerdir, ancak malzemenin hidrofobik karakteri hücre-materyal etkileşimlerini sınırlamaktadır. Bu nedenle, bu çalışma kapsamında, emülsiyon şablonlama yöntemi ile üretilmiş, polikaprolakton tetrametakrilat (4PCLMA) esaslı iskelelerin biyolojik performanslarını artırmak için iskelelerin alkali muamelesi ve elde edilen iskelelerin karakterize edilmesi amaçlanmıştır. İlk olarak halka açma polimerizasyonu ile 4PCLMA pre-polimeri sentezlenmiş ve metakrilat grupları ile fonksiyon kazandırılmıştır. 4PCLMA ~%97 metakrilasyon derecesi ile başarıyla sentezlenmiş, 4PCLMA esaslı PolyHIPE'ler emülsiyon şablonlama yöntemi ile üretilmiş, üç farklı konsantrasyonda ve inkübasyon süresinde sodyum hidroksit (NaOH) ile muamele edilmiştir. NaOH işleminin iskelelerin morfolojileri, kütle kaybı, su tutma kapasitesi, mekanik özellikleri, yüzey alanı, hidrofilisitesi ve biyolojik performansı üzerindeki etkileri araştırılmıştır. NaOH uygulamasının iskelelerin ağırlığını ve mekanik mukavemetini azalttığı ancak aynı zamanda iskelelerin su tutma kapasitesini, hidrofilisitesini, yüzey alanını ve protein adsorpsiyon kapasitesini artırdığı görülmüştür. NaOH işleminden sonra PolyHIPE'lerdeki kimyasal değişiklikler spektroskopi ile doğrulanmıştır. In vitro sonuçlar, NaOH uygulamasının L929 hücreleri üzerinde sitotoksisiteye neden olmadığını ve Saos-2 hücrelerinin tutunma ve çoğalma davranışını olumlu yönde etkilediğini göstermiştir. Bu çalışma sonucunda NaOH muamelesinin, emülsiyon şablonlama ile üretilmiş doku iskelelerinin hidrofilisitesini ve biyolojik performansını artırmak adına alternatif bir yüzey modifikasyon yöntemi olarak kullanılabileceği gösterilmiştir.Master Thesis Green Synthesis of Nanostructured Bioactive Glass for Dental Applications(01. Izmir Institute of Technology, 2023) Tüncer, Melisa; Yücesoy, Deniz Tanıl; Öksel Karakuş, CeydaBioactive glass is a biomaterial commonly used in dental care products and bone tissue engineering applications due to its biocompatibility, bone-forming ability, and remineralization capability. Bioactive glasses form a hydroxyapatite-like layer on dentinal tubules by releasing calcium and phosphorus ions after interaction with saliva. Bioactive 45S5 glass traditionally synthesized by wet chemical methods which require high-temperature heating and the use of a strong acid catalyst, bringing into question of the possibility of introducing toxic acid residues into the final product. Therefore, there is a need to develop environmental-friendly bioactive glass synthesis methods or to modify existing ones in a way to uplift their environmental friendliness. To satisfy this need, we greenized the traditional sol-gel method by replacing the acid catalyst with an environment-friendly alternative and successfully used it for the synthesis of nanostructured 45S5 bioactive glass. First, physicochemical characterization of the synthesized bioactive glasses was performed. Then, the apatite formation capability of bioglasses were investigated in saliva. Next, the mineralization kinetics of bioglasses were tested in Ca/P buffer. In vitro toxicity tests were performed to assess the cytotoxic potential of the synthesized bioactive glass. All analyses were repeated for the traditional synthesis method for comparison purposes. The results confirmed that green synthesis is more advantageous in terms of bioactivity and functionality required for dental applications. Increasing the safety and functionality of bioglass at the same time during the production phase has critical importance for ensuring the sustainability of current applications as well as creating new uses in the biomedical fieldMaster Thesis Development of a Natural Tubular Scaffold From Decellularized Parsley Stems To Be Used in Vascular Tissue Engineering Applications(01. Izmir Institute of Technology, 2024) Çevik, Merve; Dikici, Serkan; Özçivici, EnginCardiovascular diseases (CVD) are usually associated with narrowing or blockage of blood vessels and are the leading cause of death globally. By 2030, the annual incidence of CVD-related deaths is estimated to increase 23.3 million. Considering the advancements in endovascular surgery, the use of vascular grafts in cardiovascular surgery is becoming increasingly common. Autografts are the gold standard but have limitations, including limited tissue availability and complications from vessel isolation. Recently, synthetic grafts have emerged as alternatives, though they often fail due to thrombosis, atherosclerosis, intimal hyperplasia, or infection. Thrombosis, the main cause of post-implantation failure, is associated with damage or absence of the endothelial cell lining on the luminal surface of the vascular graft. To overcome the limitations mentioned so far, tissue-engineered vascular grafts (TEVG) have come into prominence. The use of decellularized plant tissues in tissue engineering applications has recently gained great importance. Accordingly, in this study, we fabricated tubular scaffolds from decellularized parsley stems and evaluated them in vitro as potential TEVGs. Our results demonstrated that native plant DNA was successfully removed, and biocompatible tubular biomaterials were successfully fabricated via chemical decellularization of parsley stems. The decellularized parsley stems showed suitable mechanical and biological properties for use as TEVG material. Finally, they were found to provide a convenient environment to form a pseudo-endothelium by recellularization with human endothelial cells prior to implantation. This study is the pioneer in the literature that reports on the potential of parsley stems to be used as a potential TEVG biomaterial.Master Thesis The Effect of Surface Modification of Biomaterials on the Cellular Interactions(Izmir Institute of Technology, 2008) Özgür, Melek; Çiftçioğlu, MuhsinThe preparation and characterization of chitosan-hydroxyapatite composite scaffolds and protein adsorption chracteristics of these scaffolds have been investigated in this study. The effects of different chitosan/hydroxyapatite contents of the low density composites on the protein adsorption behaviour were experimentally examined.Bradford method at 595 nm and 280 nm UV protein absorption methods were used for the determination of adsorbed amount of bovine serum albumin (BSA) and human serum protein (HSP). In this study low molecular weight chitosan and hydroxyapatite have been used for the preparation of the scaffold composites by freeze drying and SEM was used for microstructural analysis. The thermal behaviour of the composites was investigated by DSC and TGA. Composite scaffolds were prepared by using different amounts of chitosan and hydroxyapatite (HA) and six different scaffolds were prepared and coded as C100H0, C80H20, C70H30, C50H50, C30H70, and C20H80. The porous low density scaffolds had 93.5-96.3% porosity with a slight increase in density with increasing HA content. The interconnected pore network was formed from 50-250 .m relatively uniform size pores with thin pore walls. The HA particles were fully embedded in the polymer matrix in the pore walls. The TGA curves have shown that the freeze dried phase seperation induced biopolymer sturucture degrates at lower temperatures faster than the original raw polymer. The adsorptions of BSA and HSP onto composites have been studied as a function of time, protein concentration and pH. Adsorption experiments were also conducted with commercial HA powder. The adsorption kinetics experiments have indicated that protein adsorption was almost completely achieved in the first 2-3 hours with relatively high uptake values of up to 45-60 mg/g and 40-60 mg/g for 595 nm Bradford and 280 nm methods. The adsorption behaviour did not fit to the commonly known Langmuir and Freundlich isotherms. This was attributed to the swelling/degradation tendency of the freeze-dried chitosan containing scaffolds. The HSP uptake of 30 and 50 wt% HA containing composites were in the 50-60 mg/g range which was higher than other composites and the raw unprocessed chitosan.Master Thesis Preparation and Characterization of Sintered Ti-6a1 Powder Compacts(Izmir Institute of Technology, 2004) Çelik, Emrah; Güden, MustafaSintered Ti6Al4V powder compacts were prepared using atomized spherical and angular powders in the porosity range of 29-63%. Cylindrical green powder compacts cold compacted at various compaction pressures and then sintered at 1200 C for 2 h. The final porosities and average pore sizes were determined as functions of the applied compaction pressure and powder type. The compression deformation behavior of Ti6Al4V powder compacts was also investigated at quasi-static (1.6x10-3-1.6x10-1s-1) and high strain rate (300 and 900 s-1) conditions using conventional mechanical testing and Split Hopkinson Pressure Bar techniques, respectively. The mean pore size of the compacts varied between 29 and 171 Um depending on the particle size range of the powders used and the compaction pressure applied. Microscopic studies of as-received powders and sintered powder compacts showed that sintering at high temperature (1200oC) and subsequent relatively slow-rate cooling in the furnace transformed the microstructure of spherical powder from the acicular alpha to the Widmanstatten microstructure and angular powder from bimodal to equiaxed+ Widmanstatten microstructure.In compression testing, at both quasi-static and high strain rate conditions, the compacts failed primarily by shear band formation along the diagonal axis 45 C to the loading direction. Increasing strain rate was found to increase both the flow stress and the compressive strength of spherical powder compacts while it did not affect the critical strain for shear localization. The mechanical properties of angular powder compacts were further shown to be a function of powder size; larger the particle size higher the percentage of equiaxed structure while in compacts of particles <100 um relatively large voids resulted in reduced strength and ductility. Microscopic analyses of deformed but not failed and failed spherical powder compact samples further showed that fracture occurred in a ductile (dimpled) mode consisting of void initiation and growth in alpha phase and/or at the alpha/beta interface and macrocraking by void coalescence in the interparticle bond region. In angular powder compacts, the failure was granular brittle type at the interparticle bond region while the compact samples of particles <100 um fractured transgranularly through the voids. The strength of the sintered compacts was further shown to satisfy the strength requirements for cancellous bone replacement. The strength of the compacts having porosity level of 40% and/or lower was comparable with that of human cortical bone.Compared to Ti powder compacts of previous studies, Ti6Al4V powder compacts provided higher strength and increased porosity level of the compacts suitable for cortical bone replacement.Master Thesis Preparation and Characterization of Hydroxyopatite and Polymer Composite Biomaterials(Izmir Institute of Technology, 2002) Gültekin, Naz; Tıhmınlıoğlu, FundaIn the thesis, the preparation and characterization of polylactide-Hydroxyapatite(HA) composite films for biomaterial applications have been studied. The effects of number of parameters such as polymer type, HA loading, surface modification and its concentration on the mechanical, thermal microstructural and hydrolytic degradation properties of the composites were investigated. Four different types of polymers, Poly (L-lactide)(PLA1), 96/4 L-lactide,D-Lactide Copolymer (PDLA1), Poly (L-Lactide)(PLA2), and 67/23 Poly (L-Lactide-co-D,L-Lactide)(PDLA2), have been used. In this study, PolyLactide-HA composite films have been prepared by solvent-casting technique. The HA powder was synthesized by precipitation technique. Interfacial interactions between HA and polylactide polymer were modified to improve filler compatibility and mechanical properties of the composites by surface treatment of the HA with two different silane coupling agents; 3-aminopropyltriethoxysilane (AMPTES) and 3-mercaptopropyltrimethoxysilane (MPTMS) at three different concentration. Silane treatment indicated better dispersion of HA particles in the polymer matrix and improvements in the mechanical properties of the composites compared to the untreated HA loaded polylactide composites. Tensile test results showed that the maximum improvement in the mechanical properties of the composites was obtained for the PLA composites containing 1 wt % aminofunctional silane treated HA and 0.5 wt % mercaptopropyltrimethoxy silane treated HA for PDLA composites. Scanning electron microscopy studies also revealed better dispersion of silane treated HA particles in the polymer matrix. Thermal degradation kinetics of the composites was investigated and it was found that addition of HA into polymer matrix decreased the thermal degradation temperature and also slowed down the degradation rate. In this study, the hydrolytic degradation of poly (L-Lactide)(PLA), poly (L-Lactide-co-D-Lactide) (PDLA) and their hydroxyapatite (HA) loaded composites (10-50-w/w %) were investigated in simulated body fluid (SBF) at 37 0C and at pH 7.4 by in vitro static testing. Using different techniques, namely weighting to quantify water absorption monitored the hydrolytic degradation and weight loss, scanning electron microscopy (SEM) to observe morphological changes occurred at the surface of the films over time. At the end of the 150 days, only 12.5 wt % and 9.5 wt % of weight PLA1 and PLA2 were lost respectively. Degradation of the copolymers was faster than PLA1 and PLA2 and weight loss data of PDLA1 and PDLA2 were found to be nearly same with 17.5 wt % and 17 wt %, respectively. The changes of pH on all polymer were stable at 7.4, because of simulated body fluid indicates buffer solution properties. Degradation rate of PLA and PDLA composites containing 10 wt % HA decreased, and also water absorption of these samples increased. Weight loss decreased approximately from 12 wt % to 5 wt % and water absorption increased from 10 wt % to 13 wt % for PLA composites containing 10 wt % HA. The change of microstructural properties of obtained composites has been determined in simulated body fluid as a function of time. It was found that the surface of polymer composite films was coated with the calcium phosphate layer. This coating was increased with HA loading and ageing time.Master Thesis Preparation and Characterization of Chitosan/Calcium Phosphate Based Composite Biomaterials(Izmir Institute of Technology, 2004) Yıldırım, Oktay; Çiftçioğlu, MuhsinIn this study the preparation and characterization of three-dimensional chitosan-calcium phosphate composite structures and porous hydroxyapatite bodies for biomaterial applications have been studied. The effects of chitosan calcium phosphate amount on density, porosity, microstructure, chemical composition and mechanical properties on the composites and effects of porosifier contents, hydroxyapatite content of the slurry and sintering temperature on density, porosity and microstructure of the porous ceramic samples were investigated. SEM was used for microstructural analysis, XRD and FTIR were used for chemical analysis, Archimedes method was used for investigating physical properties and compression test for investigating mechanical properties. In this study low molecular weight chitosan, -tricalciumphosphate, hydroxyapatite and hydroxyapatite whisker have been used. For composites freeze drying technique and for the porous bodies dry pressing, polymer sponge method and dough method have been used.The densities of the composites prepared by using chitosan as the matrix and hydroxyapatite, hydroxyapatite whisker, and B-tricalciumphosphate as reinforcement increased and the porosities decreased with the increase in the ceramic content. The modulus of elasticity and the yield stress generally increased with the increasing ceramic content except for the chitosan/-tricalciumphosphate composites. The densities and porosities of the composite structures varied in the range of 0.059-0.29 g/cm3 and 96-88% respectively. The elastic moduli of the composites varied in a range of 4.45-10.09 MPa and yield stress varied in a range of 0.14-0.34 Mpa due to the change in the ceramic weight%. Changing the ceramic weight% also had influence on the microstructure. Generally with increasing ceramic content the pore sizes decreased.The pore sizes varied in a range between 100-250, 100-400 and 100-200 for chitosan/hydroxapatite, Chitosan/-TCP/Hydroxyapatite and chitosan/HA whisker composites respectively. FTIR and XRD analysis showed that the composite structures contained original constituents, no new chemical compounds were formed the production process had not affected crystallinity of ceramic phases. The densities of the porous ceramic bodies decreased and the porosities increased with the increasing porosifier content at the porous ceramics prepared by dough method and dry pressing method. The porosity and density values of porous hydroxyapatite samples changed in range of 34-72% and 2.03 to 0.87 g/cm3. Pore sizes of polymeric sponge samples were found to be around 300-400 and dry pressing and dough method samples were found to be 10u.Master Thesis Synthesis and Characterization of Hydroxyapatite-Alumina Biocomposites(Izmir Institute of Technology, 2006) Şahin, Erdem; Çiftçioğlu, MuhsinThree component hydroxyapatite-alumina-zirconia composite presents a promising candidate material for bone replacement implants. Two methods were employed to synthesize the composite that is expected to have high bioactivity, high strength and high chemical stability in physiologic environment. Wet mixing and heterogeneous precipitation methods were used for the synthesis. Commercial hydroxyapatite, alum ina and yttria stabilized zirconia were mixed in varying proportions and obtained powders were sintered upto 1300 °C subsequent to dry pressing at 160MPa. An optimum composition of 10-20-70 volume percent zirconia, alumina and hydroxyapatite respectively was found to present the most suitable proportion in terms of sinterability and phase purity. -tricalcium phosphate formation at temperatures higher than 1150 °C was found to be the only source of impurity phase in the material.Heterogeneous precipitation method was applied to synthesize a composite material with a functionally graded structure. The three components were aimed to be coated on one another, zirconia (TZ-3Y) being the core, alumina being the intermediate layer and hydroxyapatite being the outer shell. The bulk composite was expected to have both enhanced mechanical properties and enhanced phase purity due to separation of two reactive phases, hydroxyapatite and zirconia by the alumina layer. The coating was done in two steps using urea as the precipitant, aluminum sulfate as the Al3+ source, calcium nitrate as the Ca2+ source and ammonium phosphate as the P source.Precipitation of aluminum hydroxides on TZ-3Y particulates and precipitation of calcium hydroxides as a nucleation point for hydroxyapatite on cores were facilitated through decomposition of urea above 85 °C in aqueous media. Particle size, distribution and morphology were monitored for alumina coated zirconia samples prepared with varying Al2(SO4)/Zirconia and urea/Al2(SO4) molar ratios. The sample prepared with stoichiometric Al2(SO4)/Zirconia ratio and urea/Al2(SO4) ratio 10 exhibited the most suitable composition and morphology for hydroxyapatite coating. Samples synthesized in the first step were used as cores for hydroxyapatite coating.Master Thesis The Densification and Sintering Behaviour of Molten Salt Synthesized Ha Whisker/Ha Composites(Izmir Institute of Technology, 2005) Bozkurt, Suat Bahar; Çiftçioğlu, Muhsin; Çiftçioğlu, MuhsinThe hydroxyapatite (HA) whiskers were used as reinforcements in the HA powder/HA whisker (HAp/HAw) composites. The HAw was synthesized with molten salt synthesis method (MSS). NaCl, K2SO4 and NaCl-K2SO4 fluxes and HA powders were used for the synthesis of HA whiskers. The effects of various salt/HA ratios, heat treatment temperatures and time were investigated. In order to enhance the dispersibility and the elimination of the powder agglomerates ultrasonic treatment was applied to the HA-salt powder mixtures before heat treatment. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) techniques were used for the examination of the whiskers. The synthesized whiskers by using NaCl had a broad particle size range (0.25 to 40 mm in length and 0.2 to 20 mm in diameter) and similar morphologies. They had relatively larger diameters than those suitable for use as reinforcements in the HAp/HAw composites. The use of K2SO4 resulted in the formation of relatively uniform and thinner HA whiskers. The length and diameter of the whiskers varied from 5 to 90 mm and 0.5 to 10 mm, respectively. The whiskers prepared from NaCl-K2SO4 salt mixture were 12 to 110 mm in length and 0.5 to 25 mm in diameter. The HA whiskers, synthesized from NaCl-K2SO4 salt mixture and HA powder at 850°C, were selected as reinforcements for the composites because of their uniform morphology and dimensional properties. For the preparation of HAp/HAw composites, HA powder was ball milled and mixed with HAw in aqueous medium with the application of 2 h ultrasonic treatment. Sintering was carried out at 1200-1350°C range for 2 h. Pure HA powder shrunk more than the composites at all sintering temperatures and attained to 98.5% theoretical density at 1350°C. Although the density increases with sintering temperature, the density increase relative to the green structures decreases with whisker content at each sintering temperature. This may be attributed to the low shrinkage rate due to the presence of whiskers at high temperatures. The HA whiskers could be observed as embedded in the fine HA matrix for both slip cast and dry pressed samples from the SEM images. It was observed that the whiskers generally aligned in one direction except the 50% HAw-50% HAp composites.