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3D biomimetic breast cancer invasion model for testing new therapies

Funded by TUBITAK (120N422) bilateral collaboration with NCBR Poland (2021-2024)

In the frame of the current project, the combined experience of Warsaw University of Technology (WUT) and Ege University (EGE) to develop cancer intravasation-on-a-chip system, will help to understand the underlying mechanism of invasion and intravasation of cancer cells into vascular lumen. Additionally, the engineered platform might be used to establish innovative approaches in order to match patient specific cancer treatment strategies.
Development of in vitro three dimensional cerebral organoid culture based Rett Syndrome-on-a-chip model.
Funded by TUBITAK (119M578) (2019 - 2022)
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In vitro three-dimensional (3D) cell culture studies that mimic in vivo physiology and tissue microenvironment for pre-clinical evaluation of the efficacy and safety of potential new drugs have become imperative for modelling various diseases, mainly hereditary, infectious, neurodegenerative, neurodevelopmental and cancer. 3D cell culture techniques that overcome the inadequacy of traditional two-dimensional models are not only new tools in drug discovery, but also potential models for the treatment of diseases. The proposed project will be based on development of organoid cultures and adapted to organ-on-chip systems. Organoids are 3D multicellular tissue structures that can be widely self-organized by pluripotent stem cell-derived cells and mimic the in vivo conditions in a physiological and functional manner. Organ-on-a-chip platforms can recapitulate the mechano-transduction effect on the cells, provide control over physiological stress, chemical signaling, and cell-cell interactions, while reducing the consumption of nutrients and ensuring cells are studied under physiological fluid flow conditions. The focus of the project is on developing a microphysiologically relevant in vitro model for Rett syndrome, which is a dominant inherited X-linked neurodevelopmental disorder in the group of genetic rare diseases (1/10,000-15,000) that almost exclusively affect girls. The project led by Dr. Yesil-Celiktas at Bioengineering Department of Ege University is truly interdisciplinary, with collaborators from Faculty of Medicine and Izmir Biomedicine and Genome Center.
In vitro 3D model development for the assessment of immune response towards implantable biomaterials in cartilage defects.
Funded by TUBITAK (219M057) (2020 - 2021)
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Biomaterials are natural or synthetic materials designed to interact with biological systems for a medical purpose and used to replace, renew, repair or strengthen any body part, tissue or organ in terms of structure and / or function. The global implantable biomaterials market is expected to reach $ 195.47 billion in 2026. Immune cells in the system react sensitively against all foreign materials entering the body, including biomaterials. These immune cells develop an immune response against biomaterials implanted in the body for purposes such as destroying all factors that are foreign and pathogenic to the body, trying to keep them separate from the body by limiting indestructible factors, and providing the necessary stimulation for wound healing. The aim of the project is to produce a three-dimensional cell microenvironment that can mimic the in vivo foreign body response. A hydrogel-based model containing different cell types that allow in vitro testing of cytoskeleton produced for cartilage damage is developed and foreign body response to various biomaterials developed for cartilage repair are investigated.

Synthesis of a novel stiff hydrogel for cartilage tissue engineering functionalized with nanoparticles fabricated by using a microfluidic platform along with in vivo studies. 

Funded by TUBITAK (117M843), bilateral collaboration with NRF-South Korea, (2018-2020)

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Degeneration in the cartilage occurs in the joints when the articular cartilage begins to degrade. While this type of degeneration is often related to aging, a variety of other factors are effective as well such as obesity, lack of exercise, genetic predisposition, bone density, occupational injury, trauma and gender. The severe cases result in bones rubbing together and creating stiffness, pain, and impaired movement. According to the United Nations report, 130 million people will suffer from osteoarthritis worldwide by 2050, of whom 40 million will be severely disabled by the disease. Costs associated with this pathology include costs for adaptive aids and devices, medicines, surgery, and time off at work. While protective factors such as exercise, healthy diet, and occupational injuries can all be addressed, many risk factors such as gender, age, and genetics are not modifiable. The physical disability arising from pain and loss of functional capacity reduces quality of life and increases the risk of further morbidity. Although there is a wide range of devices and palliative medicines available that can relieve pain and improve quality of life, there is a need for novel and stiff biocompatible materials that can replace cartilage. Based on this requirement, the formulation of a stiff hydrogel functionalized with TGF-β3 encapsulated nanoparticles to serve as a cartilage implant with improved mechanical and biological properties is proposed. PLGA nanoparticles was fabricated using a microfluidic platform in a continues mode. Subsequent to the formation of the functionalized hydrogel, biocompatibility testing was applied in order to investigate the interaction between the hydrogel and the cells. Besides, in vivo experiments with an osteochondral defect model was utilized to gain more insight based on histological cartilage assessment to evaluate new cartilage formation and healing.
Enzymatic reactions in micro devices with a focus on sol-gel technology: experimental study and model development. 
Funded by TUBITAK (113M050), bilateral collaboration with BMBF Germany, (2014-2017)
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Main goal of the  this project was to develop and model microfludic systems to perform enzymatic hydrolysis of saponin glycosides. Organic, inorganic and hybrid based gel formulations have been studied for immobilizing b-glucoosidase and b-glucuronidase enzymes. Formulated gels were well characterized by aging, shrinkage, surface area, Scaning Electron Microscopy (SEM) and FTIR measurements. Additionally enzyme kinetics for 4-nitrophenyl β-D-glucopyranoside and 4-nitrophenyl β-D-glucopuronide, which are used as model substrates, were determined. Optimized gels have been loaded into 4 different microchannel reactors (1 PDMS and 3 glass-silicone) and enzymatic reaction was performed.   Enzymatic conversion of selected saponins; ginsenoside Rb1 and Rg1, glycyrrhizic acid soyasaponin Aa and  Bb, baicalin, Ruscus saponin extract were conducted in the microsytems. As result of the enzymatic conversions various intermediate product and aglycone of baicalin obtained. However in conventional acidic and basic reactions many by-products and artefacts, which are unwanted, have been detected. Comparing to    reactions with free enzymes, conversion yield of immobilized enzymes in microchannels were found higher. The results show that the enzymatic raction s are more spesific than conventional chemical reactions. On the other hand, due to better diffusion effects in microsytems, reaction in microchannel was more advantagous.  Besides mathematical models for diiffusion of substrate molecules inside loaded microchannels and the enzymatic reaction was developed. As a conclusion comprehensive knowledge about preparing different gel formulations for enzyme immobilization, design and fabrication of microfluidic systems and enzymtaic reacion in microchannel reactor have been achieved during this project. 
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Sustainable Polymers from Algae Sugars and Hydrocarbons (SPLASH)
Funded by EU FP7, Contact for Turkish partner, (2012-2017)

Ege University
Department of Bioengineering

35040 Bornova-Izmir/TURKEY

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