Bioengineering / Biyomühendislik

Permanent URI for this collectionhttps://hdl.handle.net/11147/4529

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  • Review
    Citation - WoS: 23
    Citation - Scopus: 24
    Microfluidic-Based Technologies for Diagnosis, Prevention, and Treatment of Covid-19: Recent Advances and Future Directions
    (Springer, 2023) Tarım, Ergün Alperay; Anıl İnevi, Müge; Özkan, İlayda; Keçili, Seren; Bilgi, Eyüp; Başlar, Muhammet Semih; Özçivici, Engin; Öksel Karakuş, Ceyda; Tekin, Hüseyin Cumhur
    The COVID-19 pandemic has posed significant challenges to existing healthcare systems around the world. The urgent need for the development of diagnostic and therapeutic strategies for COVID-19 has boomed the demand for new technologies that can improve current healthcare approaches, moving towards more advanced, digitalized, personalized, and patient-oriented systems. Microfluidic-based technologies involve the miniaturization of large-scale devices and laboratory-based procedures, enabling complex chemical and biological operations that are conventionally performed at the macro-scale to be carried out on the microscale or less. The advantages microfluidic systems offer such as rapid, low-cost, accurate, and on-site solutions make these tools extremely useful and effective in the fight against COVID-19. In particular, microfluidic-assisted systems are of great interest in different COVID-19-related domains, varying from direct and indirect detection of COVID-19 infections to drug and vaccine discovery and their targeted delivery. Here, we review recent advances in the use of microfluidic platforms to diagnose, treat or prevent COVID-19. We start by summarizing recent microfluidic-based diagnostic solutions applicable to COVID-19. We then highlight the key roles microfluidics play in developing COVID-19 vaccines and testing how vaccine candidates perform, with a focus on RNA-delivery technologies and nano-carriers. Next, microfluidic-based efforts devoted to assessing the efficacy of potential COVID-19 drugs, either repurposed or new, and their targeted delivery to infected sites are summarized. We conclude by providing future perspectives and research directions that are critical to effectively prevent or respond to future pandemics.
  • Article
    Citation - WoS: 22
    Citation - Scopus: 24
    Scaffold-Free Biofabrication of Adipocyte Structures With Magnetic Levitation
    (John Wiley and Sons Inc., 2021) Sarıgil, Öykü; Yalçın Özuysal, Özden; Anıl İnevi, Müge; Meşe Özçivici, Gülistan; Fıratlıgil Yıldırır, Burcu; Fıratlıgil Yıldırır, Burcu; Ünal, Yağmur Ceren; Ünal, Yağmur Ceren; Yalçın Özuysal, Özden; Özçivici, Engin; Meşe, Gülistan; Sarıgil, Öykü; Özçivici, Engin; Anıl İnevi, Müge; Meşe Özçivici, Gülistan
    Tissue engineering research aims to repair the form and/or function of impaired tissues. Tissue engineering studies mostly rely on scaffold-based techniques. However, these techniques have certain challenges, such as the selection of proper scaffold material, including mechanical properties, sterilization, and fabrication processes. As an alternative, we propose a novel scaffold-free adipose tissue biofabrication technique based on magnetic levitation. In this study, a label-free magnetic levitation technique was used to form three-dimensional (3D) scaffold-free adipocyte structures with various fabrication strategies in a microcapillary-based setup. Adipogenic-differentiated 7F2 cells and growth D1 ORL UVA stem cells were used as model cells. The morphological properties of the 3D structures of single and cocultured cells were analyzed. The developed procedure leads to the formation of different patterns of single and cocultured adipocytes without a scaffold. Our results indicated that adipocytes formed loose structures while growth cells were tightly packed during 3D culture in the magnetic levitation platform. This system has potential for ex vivo modeling of adipose tissue for drug testing and transplantation applications for cell therapy in soft tissue damage. Also, it will be possible to extend this technique to other cell and tissue types.
  • Article
    Citation - WoS: 79
    Citation - Scopus: 93
    Magnetic Force-Based Micro Fluidic Techniques for Cellular and Tissue Bioengineering
    (Frontiers Media S.A., 2018) Yaman, Sena; Anıl İnevi, Müge; Özçivici, Engin; Tekin, Hüseyin Cumhur
    Live cell manipulation is an important biotechnological tool for cellular and tissue level bioengineering applications due to its capacity for guiding cells for separation, isolation, concentration, and patterning. Magnetic force-based cell manipulation methods offer several advantages, such as low adverse effects on cell viability and low interference with the cellular environment. Furthermore, magnetic-based operations can be readily combined with microfluidic principles by precisely allowing control over the spatiotemporal distribution of physical and chemical factors for cell manipulation. In this review, we present recent applications of magnetic force-based cell manipulation in cellular and tissue bioengineering with an emphasis on applications with microfluidic components. Following an introduction of the theoretical background of magnetic manipulation, components of magnetic force-based cell manipulation systems are described. Thereafter, different applications, including separation of certain cell fractions, enrichment of rare cells, and guidance of cells into specific macro- or micro-arrangements to mimic natural cell organization and function, are explained. Finally, we discuss the current challenges and limitations of magnetic cell manipulation technologies in microfluidic devices with an outlook on future developments in the field.
  • Article
    Citation - WoS: 34
    Citation - Scopus: 43
    Label-Free Density-Based Detection of Adipocytes of Bone Marrow Origin Using Magnetic Levitation
    (Royal Society of Chemistry, 2019) Sarıgil, Öykü; Anıl İnevi, Müge; Yılmaz, Esra; Meşe, Gülistan; Tekin, Hüseyin Cumhur; Özçivici, Engin
    Adipocyte hypertrophy and hyperplasia are important parameters in describing abnormalities in adipogenesis that are concomitant to diseases such as obesity, diabetes, anorexia nervosa and osteoporosis. Therefore, technical developments in the detection of adipocytes become an important driving factor in adipogenesis research. Current techniques such as optical microscopy and flow cytometry are available in detection and examination of adipocytes, driving cell- and molecular-based research of adipogenesis. Even though microscopy techniques are common and straightforward, they are restricted in terms of manipulation and separation of the cells. Flow cytometry is an alternative, but mature adipocytes are fragile and cannot withstand the flow process. Other separation methods usually require labeling of the cells or usage of microfluidic platforms that utilize fluids with different densities. Magnetic levitation is a novel label-free technology with the principle of movement of cells towards the lower magnetic field in a paramagnetic medium depending on their individual densities. In this study, we used a magnetic levitation device for density-based single cell detection of differentiated adipogenic cells in heterogeneous populations. Results showed that the magnetic levitation platform was sensitive to changes in the lipid content of mesenchymal stem cells committed to adipogenesis and it could be successfully used to detect the adipogenic differentiation of the cells.
  • Article
    Citation - WoS: 6
    Citation - Scopus: 7
    A Biodesign Approach To Obtain High Yields of Biosimilars by Anti-Apoptotic Cell Engineering: A Case Study To Increase the Production Yield of Anti-Tnf Alpha Producing Recombinant Cho Cells
    (Humana Press, 2018) Gülce İz, Sultan; Anıl İnevi, Müge; Sağlam Metiner, Pelin; Ayyıldız Tamiş, Duygu; Kisbet, Nazlı
    Recent developments in medical biotechnology have facilitated to enhance the production of monoclonal antibodies (mAbs) and recombinant proteins in mammalian cells. Human mAbs for clinical applications have focused on three areas, particularly cancer, immunological disorders, and infectious diseases. Tumor necrosis factor alpha (TNF-α), which has both proinflammatory and immunoregulatory functions, is an important target in biopharmaceutical industry. In this study, a humanized anti-TNF-α mAb producing stable CHO cell line which produces a biosimilar of Humira (adalimumab) was used. Adalimumab is a fully human anti-TNF mAb among the top-selling mAb products in recent years as a biosimilar. Products from mammalian cell bioprocesses are a derivative of cell viability and metabolism, which is mainly disrupted by cell death in bioreactors. Thus, different strategies are used to increase the product yield. Suppression of apoptosis, also called anti-apoptotic cell engineering, is the most remarkable strategy to enhance lifetime of cells for a longer production period. In fact, using anti-apoptotic cell engineering as a BioDesign approach was inspired by nature; nature gives prolonged life span to some cells like stem cells, tumor cells, and memory B and T cells, and researchers have been using this strategy for different purposes. In this study, as a biomimicry approach, anti-apoptotic cell engineering was used to increase the anti-TNF-α mAb production from the humanized anti-TNF-α mAb producing stable CHO cell line by Bcl-xL anti-apoptotic protein. It was shown that transient transfection of CHO cells by the Bcl-xL anti-apoptotic protein expressing plasmid prolonged the cell survival rate and protected cells from apoptosis. The transient expression of Bcl-xL using CHO cells enhanced the anti-TNF-α production. The production of anti-TNF-α in CHO cells was increased up to 215 mg/L with an increase of 160% after cells were transfected with Bcl-xL expressing plasmid with polyethylenimine (PEI) reagent at the ratio of 1:6 (DNA:PEI). In conclusion, the anti-apoptotic efficacy of the Bcl-xL expressing plasmid in humanized anti-TNF-α MAb producing stable CHO cells is compatible with curative effect for high efficiency recombinant protein production. Thus, this model can be used for large-scale production of biosimilars through transient Bcl-xL gene expression as a cost-effective method.