Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection

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  • Article
    Citation - WoS: 51
    Citation - Scopus: 60
    Biosilica Incorporated 3d Porous Scaffolds for Bone Tissue Engineering Applications
    (Elsevier Ltd., 2018) Tamburacı, Sedef; Tıhmınlıoğlu, Funda; Tıhmınlıoğlu, Funda; 03.02. Department of Chemical Engineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
    As a natural and abundant silica mineral, diatomite particles (SiO2-nH2O) have been used in several areas such as filtration, photonics, sound and heat insulation, filler material and drug delivery due to its abundance, inexpensive cost, unique morphology and porous structure. But up to date, diatomite incorporated silica based scaffolds have not been used for bone tissue engineering applications. In the present study, the goal was to combine the useful biomaterial properties of both chitosan and diatomite as biocomposite organic/inorganic biomaterial for bone tissue engineering applications and optimize the silica content of the composites in order to obtain optimum morphological structure, high mechanical properties, enlarged surface area and enhanced cell proliferation. The effect of silica loading on the mechanical, morphological, chemical, and surface properties, wettability and biocompatibility of composite scaffolds were investigated. In addition, in vitro cytotoxicity and cellular activities including cell proliferation, ALP activity and biomineralization were investigated in order to determine biological activity of the composite scaffolds. Diatomite particles lead to enhancement in the water uptake capacity of scaffolds. Chitosan-silica composites exhibited 82–90% porosity. Wet chitosan-silica composite scaffolds exhibited higher compression moduli when compared to pure chitosan scaffold in the range of 67.3–90.1 kPa. Average pore size range of chitosan-diatomite composite scaffolds was obtained as 218-319 μm. In vitro results indicated that chitosan-diatomite composites did not show any cytotoxic effect on 3T3, MG-63 and Saos-2 cell lines. Scaffolds were found to be favorable for osteoblast proliferation. Diatomite incorporation showed promising effects on enhancing ALP activity as well as mineral formation on scaffold surface. Thus, the prepared scaffolds in this study can be considered prospective material for bone tissue engineering applications.
  • 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; Anıl İnevi, Müge; Ayyıldız Tamiş, Duygu; Kisbet, Nazlı; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
    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.