Phd Degree / Doktora

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

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Author: search.filters.author.Tıhmınlıoğlu, Funda

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  • Doctoral Thesis
    Development and Characterization of Novel Bioink by Using Decellularized Extracellular Matrix for Bone Tissue Engineering Applications
    (01. Izmir Institute of Technology, 2023) Kara Özenler, Aylin; Tıhmınlıoğlu, Funda; Havıtçıoğlu, Hasan
    Bone tissue engineering has focused on the development of functional scaffolds that can organize bone regeneration with appropriate structures and properties. Three-dimensional (3D) printing technology enables the development of personalized scaffolds. In addition, biological scaffolds obtained by decellularization have various advantages for developing natural-based scaffolds. The development of printable, patient-specific bioinks derived from decellularized extracellular matrix could provide 3D fabrication of tissues and organs with high potential to mimic native tissues. The presented thesis study demonstrates the development of various bioink compositions for bone tissue engineering applications. In this regard, bone tissues were decellularized with a novel method and then characterized in order to verify the removal of whole cellular components for eliminating immunological reactions. After the pulverization of tissues, decellularized bone (DB) particles were used as an additive within various ink combinations (alginate-, gelatin- and alginate-gelatin-based). Thus, various bioink formulations were developed containing DB particles, biopolymers and mesenchymal stem cells (MSC). All prepared bioinks were bioprinted, then the viability, proliferation and differentiation capacity of the cells inside the structures as well as the physical, rheological, and printability properties of the inks were assessed. The results revealed that all bioink combinations were suitable for bioprinting and the addition of DB particles improved cell proliferation and osteogenic differentiation in all bioink formulations. Alginate-based bioinks exhibited the greatest printability and shape fidelity, gelatin-based bioinks showed the highest cell proliferation and attachment, also, gelatin incorporation into alginate-based bioinks improved the biological activity of cells. In conclusion, cytocompatible, functional composite bioinks developed in this thesis study are of value for bone tissue engineering research in future to explore their functions in the living system and show complete bone regeneration while maintaining their stability for a long time.
  • Doctoral Thesis
    Macromolecular Design of Hydroxyl Functional Linear and Star-Shaped L-Lactide and ?-Caprolactone Biodegradable Polyesters Utilizing Biosafe Catalysts for Biomedical Applications
    (Izmir Institute of Technology, 2017) Başalp, Dildare; Tıhmınlıoğlu, Funda
    In the present study, macromolecular design of homo and copolymers of lactide (LA) and ε-caprolactone (CL) in different structures by the use of biocompatible catalysts and co-initiators were performed to satisfy a need of tailor-made bioassimilable polymeric structures without any hazardous metal contaminants for various medical applications. Linear and star shaped (di, tetra and hexa functional) poly(L-lactide) (PLLA) and poly(ε-caprolactone) (PCL) homo/copolymers were synthesized by using bismuth(III)acetate (Bi(III)Ac) and creatinine as biosafe catalysts and ethylene glycol, pentaerythritol and myo-inositol as co-initiators. The effect of catalyst type on polymer properties was observed by differences in crystalline structure. Crystalline and amorphous linear and star shaped PLLAs were obtained by using Bi(III)Ac and creatinine as catalysts, respectively. The activity of creatinine was very low comparing to Bi(III)Ac and SnOct2 catalysts. The reactivity of LA monomer was found to be higher than that of CL monomer. The high molecular weight polymers having low PDI values were obtained by using Bi(III)Ac catalyst contary to creatinine catalyst. The decrease in glass transition temperatures and molecular weights of synthesized PLLA and PCL homo/copolymers were observed with the increase in amount of co-initiators due to the decrease in chain length and disruption of crystal formation. The cytotoxicity properties of the catalysts and synthesized linear and functional homo/co PLLAs and PCLs were carried out according to MTT assay. Cytotoxicity of Bi(III)Ac was found as lower than that of SnOct2. Creatinine and the synthesized polymers did not show any cytotoxic properties. The observation of no cytotoxic effect of creatinine catalyst results in the biosafe usage of creatinine catalyst instead of toxic SnOct2 for the synthesis of moderate or low molecular weight homo/co PLLAs and PCLs in bioapplications.
  • Doctoral Thesis
    Development of Novel Chitosan Nanocomposites as a Controlled Drug Release System for Helicobacter Pylori Treatment
    (İzmir Institute of Technology, 2016) Güneş, Suna Seda; Tıhmınlıoğlu, Funda; Yılmaz, Özlem
    Helicobacter pylori is one of the most common bacterial infection and responsible for gastroduodenal diseases in humans. Due to increasing failure rate of currently used antibiotic therapies, newer drugs and therapeutic approaches are needed. Therefore the use of encapsulated cinnamon bark oil is a promising approach for H. pylori eradication. The main objective of this dissertation was to develop a novel drug delivery system using chitosan and nanoclay containing cinnamon bark oil to be released in a controlled manner in gastrointestinal system for H. pylori eradication as an alternative or complementary to conventional antibiotic treatment. Minimum inhibition concentration (MIC) value of cinnamon bark oil was determined. Cinnamon bark oil loaded chitosan nanocomposite microspheres were produced by spray drying. The prepared microspheres were characterized for particle size & morphology, encapsulation efficiency, surface charge, mucoadhesion, degradation, swelling and drug release. Antimicrobial activity of the microspheres against H. pylori were investigated. In vitro cell viability of fibroblast and gastric epithelial cells were evaluated. In vitro cellular uptake and binding studies of microspheres were investigated by using gastric epithelial cells. MIC value of cinnamon bark oil was found as 8 μg/mL. Nanoclay incorporation decreased the biodegradation of nanocomposite microspheres and improved the release of cinnamon bark oil. Drug release mechanism was anomalous diffusion which refers to combination of diffusion and erosion controlled. The prepared microspheres showed strong mucoadhesive property. Oil released from prepared microspheres inhibited H. pylori growth. Although cinnamon oil showed cytotoxic effect above 31 μg/mL, the oil encapsulated chitosan microspheres did not show any cytotoxic effect on NIH3T3 and MKN45 cells. The prepared microspheres were able to get internalized into MKN45 cells and had great incorporation activity. The results of this study demonstrated that cinnamon bark oil loaded chitosan nanocomposites may serve as biocompatible and effective gastroretentive drug carrier for the treatment of H. pylori infection.
  • Doctoral Thesis
    Natural and Synthetic Silica Incorporated Chitosan Composite Scaffolds for Bone Tissue Engineering Applications
    (İzmir Institute of Technology, 2016) Tamburacı, Sedef; Tıhmınlıoğlu, Funda; Tıhmınlıoğlu, Funda; Havıtçıoğlu, Hasan
    Recently bone tissue engineering studies have focused on the development of 3D scaffolds that can organize the tissue regeneration in natural way with appropriate porosity and reinforced the structure. Natural polymer-based composites have been focused with more attention than synthetic polymer composites for bone tissue engineering applications because of their biocompatibility and biodegradability. In this work, the goal was to combine the useful biomaterial properties of both chitosan and silica to design biocomposite organic/inorganic biomaterials for bone tissue engineering applications. The composite scaffolds were fabricated by freeze drying method bu using two different silicas; natural silica; Diatomite and synthetic silica, octa (tetramethylammonium) polyhedral oligomeric silsesquioxanes (OctaTMA-POSS). The effects of silica type and loading on the mechanical, morphological, chemical, surface properties, wettability and biocompatibility of composite scaffolds were investigated and characterized by using SEM, AFM, contact angle analysis, swelling study, protein adsorption assay, biodegradation and biomineralization tests. WST-1 cytotoxicity, cell proliferation with rezasurin and alkaline phosphatase activity assays were performed to determine biological activity of the composite scaffolds. In vitro biomineralization on scaffolds was determined by Von Kossa and Alizarin red staining. POSS and diatomite incorporation increased the surface roughness. Chitosansilica composites exhibited 82-90% porosity. Wet chitosan-silica composite scaffolds exhibited higher compression moduli compared to pure chitosan scaffold in 67.3- 81.4kPa and 78.1 to 107.6kPa range respectively. Average pore size range of chitosandiatomite and chitosan-POSS composite scaffolds was obtained as 15-180μm and 220- 300μm, respectively. Results indicated that chitosan-silica composites did not show any cytotoxic effect on 3T3, MG-63 and Saos-2 cell lines. Chitosan-silica composites were found to be favorable for osteoblast proliferation. Diatomite and POSS incorporation showed promising effects with enhancing ALP activity on hFob cells. Therefore, these composite scaffolds could be used for bone tissue engineering applications.
  • Doctoral Thesis
    Preparation and Evaluation of Chitosan Microspheres for Eradication of Helicobacter Pylori
    (Izmir Institute of Technology, 2011) Altıok, Duygu; Tıhmınlıoğlu, Funda
    The main focus of this dissertation is to develop chitosan based microspheres loaded with antibiotic and essential oil to eradicate Helicobacter pylori by maintaining the constant drug level and prolonged gastric retention. The primary objective was to show that novel essential oil loaded microspheres are promising in the treatment of H. pylori infection as an alternative to conventional antibiotic therapy. In this context, firstly, the minimum inhibitory concentration of clarithromycin and five essential oils namely lemongrass oil, thyme oil, clove leaf oil, lemon oil and cinnamon bark oil on H. pylori was investigated. Among five essential oils, cinnamon bark oil showed the strongest anti-H. pylori activity. After choosing the most effective essential oil on H. pylori, we focused on the preparation of clarithromycin and cinnamon bark oil loaded microspheres by spray drying technique. Spray drying conditions were optimized by reponse surface methodology. Genipin, a natural crosslinker, was used as a crosslinking agent to achieve controlled drug release. Finally, it was aimed to investigate the clarithromycin and essential oil release in buffer solution and their antibacterial activity on H. pylori when released from microspheres. Higuchi equation well described the release characteristics. Drug release from microspheres was diffusion controlled. Cinnamon bark oil and clarithromycin released from the microspheres inhibited the growth of H. pylori resulting that the antibacterial activity of cinnamon bark oil and clarithromycin was maintained during the microsphere manufacturing. In conclusion, clarithromycin and cinnamon bark oil loaded chitosan microspheres have a great potential to be used as a control release system in treatment of H. pylori infection.