Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
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Review Citation - WoS: 23Citation - Scopus: 24Microfluidic-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 CumhurThe 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: 14Lamin A/C Is Dispensable To Mechanical Repression of Adipogenesis(MDPI, 2021) Goelzer, Matthew; Dudakovic, Amel; Olçum, Melis; Sen, Buer; Özçivici, Engin; Rubin, Janet; van Wijnen, Andre J.Mesenchymal stem cells (MSCs) maintain the musculoskeletal system by differentiating into multiple lineages, including osteoblasts and adipocytes. Mechanical signals, including strain and low-intensity vibration (LIV), are important regulators of MSC differentiation via control exerted through the cell structure. Lamin A/C is a protein vital to the nuclear architecture that supports chromatin organization and differentiation and contributes to the mechanical integrity of the nucleus. We investigated whether lamin A/C and mechanoresponsiveness are functionally coupled during adipogenesis in MSCs. siRNA depletion of lamin A/C increased the nuclear area, height, and volume and decreased the circularity and stiffness. Lamin A/C depletion significantly decreased markers of adipogenesis (adiponectin, cellular lipid content) as did LIV treatment despite depletion of lamin A/C. Phosphorylation of focal adhesions in response to mechanical challenge was also preserved during loss of lamin A/C. RNA-seq showed no major adipogenic transcriptome changes resulting from LIV treatment, suggesting that LIV regulation of adipogenesis may not occur at the transcriptional level. We observed that during both lamin A/C depletion and LIV, interferon signaling was downregulated, suggesting potentially shared regulatory mechanism elements that could regulate protein translation. We conclude that the mechanoregulation of adipogenesis and the mechanical activation of focal adhesions function independently from those of lamin A/C.Article Citation - WoS: 21Citation - Scopus: 22Daily Application of Low Magnitude Mechanical Stimulus Inhibits the Growth of Mda-Mb Breast Cancer Cells in Vitro(BioMed Central Ltd., 2014) Ölçüm, Melis; Özçivici, EnginIntroduction: Mechanical loads can regulate cell proliferation and differentiation at various stages of development and homeostasis. However, the extension of this regulatory effect of mechanical loads on cancer cells is largely unknown. Increased physical compliance is one of the key features of cancer cells, which may hamper the transmission of mechanical loads to these cells within tumor microenvironment. Here we tested whether brief daily application of an external low magnitude mechanical stimulus (LMMS), would impede the growth of MDA-MB-231 aggressive type breast cancer cells in vitro for 3 wks of growth. Methods: The signal was applied in oscillatory form at 90 Hz and 0.15 g, a regimen that would induce mechanical loads on MDA-MB-231 cells via inertial properties of cells rather than matrix deformations. Experimental cells were exposed to LMMS 15 min/day, 5 days/week in ambient conditions while control cells were sham loaded. Cell proliferation, viability, cycle, apoptosis, morphology and migration were tested via Trypan Blue dye exclusion, MTT, PI, Annexin V, Calcein-AM and phalloidin stains and scratch wound assays. Results: Compared to sham controls, daily application of LMMS reduced the number and viability of cancerous MDA-MB-231 cells significantly after first week in the culture, while non-cancerous MCF10A cells were found to be unaffected. Flow cytomety analyses suggested that the observed decrease for the cancer cells in the LMMS group was due to a cell cycle arrest rather than apoptosis. LMMS further reduced cancer cell circularity and increased cytoskeletal actin in MDA-MB-231 cells. Conclusion: Combined, results suggest that direct application of mechanical loads negatively regulate the proliferation of aggressive type cancer cells. If confirmed, this non-invasive approach may be integrated to the efforts for the prevention and/or treatment of cancer.Article Citation - WoS: 5Citation - Scopus: 5Low Magnitude High Frequency Vibrations Expedite the Osteogenesis of Bone Marrow Stem Cells on Paper Based 3d Scaffolds(Springer, 2020) Karadaş, Özge; Meşe, Gülistan; Özçivici, EnginAnabolic effects of low magnitude high frequency (LMHF) vibrations on bone tissue were consistently shown in the literature in vivo, however in vitro efforts to elucidate underlying mechanisms are generally limited to 2D cell culture studies. Three dimensional cell culture platforms better mimic the natural microenvironment and biological processes usually differ in 3D compared to 2D culture. In this study, we used laboratory grade filter paper as a scaffold material for studying the effects of LHMF vibrations on osteogenesis of bone marrow mesenchymal stem cells in a 3D system. LMHF vibrations were applied 15 min/day at 0.1 g acceleration and 90 Hz frequency for 21 days to residing cells under quiescent and osteogenic conditions. mRNA expression analysis was performed for alkaline phosphatase (ALP) and osteocalcin (OCN) genes, Alizarin red S staining was performed for mineral nodule formation and infrared spectroscopy was performed for determination of extracellular matrix composition. The highest osteocalcin expression, mineral nodule formation and the phosphate bands arising from the inorganic phase was observed for the cells incubated in osteogenic induction medium with vibration. Our results showed that filter paper can be used as a model scaffold system for studying the effects of mechanical loads on cells, and LMHF vibrations induced the osteogenic differentiation of stem cells.Article Citation - WoS: 28Citation - Scopus: 30Bone Marrow Stem Cells Adapt To Low-Magnitude Vibrations by Altering Their Cytoskeleton During Quiescence and Osteogenesis(TUBITAK, 2015) Demiray, Levent; Özçivici, EnginApplication of mechanical vibrations is anabolic to bone tissue, not only by guiding mature bone cells to increased formation, but also by increasing the osteogenic commitment of progenitor cells. However, the sensitivity and adaptive response of bone marrow stem cells to this loading regimen has not yet been identified. In this study, we subjected mouse bone marrow stem cell line D1-ORL-UVA to daily mechanical vibrations (0.15 g, 90 Hz, 15 min/day) for 7 days, both during quiescence and osteogenic commitment, to identify corresponding ultrastructural adaptations on cellular and molecular levels. During quiescence, mechanical vibrations significantly increased total actin content and actin fiber thickness, as measured by phalloidin staining and fluorescent microscopy. Cellular height also increased, as measured by atomic force microscopy, along with the expression of focal adhesion kinase (PTK2) mRNA levels. During osteogenesis, mechanical vibrations increased the total actin content, actin fiber thickness, and cytoplasmic membrane roughness, with significant increase in Runx2 mRNA levels. These results show that bone marrow stem cells demonstrate similar cytoskeletal adaptations to low-magnitude high-frequency mechanical loads both during quiescence and osteogenesis, potentially becoming more sensitive to additional loads by increased structural stiffness.Book Part Citation - Scopus: 15Stem Cell Culture Under Simulated Microgravity(Springer, 2020) Anıl İnevi, Müge; Sarıgil, Öykü; Kızılkaya, Melike; Meşe, Gülistan; Tekin, Hüseyin Cumhur; Özçivici, EnginChallenging environment of space causes several pivotal alterations in living systems, especially due to microgravity. The possibility of simulating microgravity by ground-based systems provides research opportunities that may lead to the understanding of in vitro biological effects of microgravity by eliminating the challenges inherent to spaceflight experiments. Stem cells are one of the most prominent cell types, due to their self-renewal and differentiation capabilities. Research on stem cells under simulated microgravity has generated many important findings, enlightening the impact of microgravity on molecular and cellular processes of stem cells with varying potencies. Simulation techniques including clinostat, random positioning machine, rotating wall vessel and magnetic levitation-based systems have improved our knowledge on the effects of microgravity on morphology, migration, proliferation and differentiation of stem cells. Clarification of the mechanisms underlying such changes offers exciting potential for various applications such as identification of putative therapeutic targets to modulate stem cell function and stem cell based regenerative medicine. © Springer Nature Switzerland AG 2020.Article Citation - WoS: 8Citation - Scopus: 11Application of Low Intensity Mechanical Vibrations for Bone Tissue Maintenance and Regeneration(TÜBİTAK, 2016) Ölçüm, Melis; Baskan, Öznur; Karadaş, Özge; Özçivici, EnginPhysical exercise is beneficial for bone tissue health, yet its usage is limited for preventing osteoporosis. Even though natural for the bone tissue from development to homeostasis, mechanical loads present with a multitude of physical parameters, including amplitude, duration, frequency, and distribution. Utilizing the most beneficial parameters of mechanical loads may potentiate a nonpharmaceutical tool for biotechnology to prevent and treat bone loss related to aging, bedrest, sedentary lifestyles, weightlessness, and other diseases. Low intensity vibrations (LIVs) consist of mechanical loads with amplitudes smaller than loads prescribed by habitual activity, with a higher frequency. In this review, literature covering LIV signal application on bone tissue and cellular and molecular level is presented. Studies indicate that LIV signals are safe, anabolic, and anticatabolic for skeletal tissue and are of great significance in regenerative medicine applications.Article Citation - WoS: 79Citation - Scopus: 93Magnetic Force-Based Micro Fluidic Techniques for Cellular and Tissue Bioengineering(Frontiers Media S.A., 2018) Yaman, Sena; Anıl İnevi, Müge; Özçivici, Engin; Tekin, Hüseyin CumhurLive 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.Conference Object Genetic Determinants of Musculoskeletal Adaptations To Unloading and Reloading(Institute of Electrical and Electronics Engineers Inc., 2019) Özçivici, Engin; Judex, StefanLack of weight bearing is one of the most critical limitations for long term health of bone tissue in space missions. In this study, we performed a series of Quantitative Trait Locus (QTL) analysis of musculoskeletal traits to define genomic modulators adaptations to mechanical unloading and subsequent reloading using a genetically heterogeneous (F2 BALBxC3H) female mouse population. The identified regions on genome contain genes that regulate musculoskeletal adaptations to weightlessness and further studies may help to categorize individuals that are at risk for greater tissue loss during weightlessness and/or low tissue recovery during reambulation.Conference Object Citation - WoS: 5Citation - Scopus: 8Lensless Digital In-Line Holographic Microscopy for Space Biotechnology Applications(Institute of Electrical and Electronics Engineers Inc., 2019) Delikoyun, Kerem; Çine, Ersin; Anıl İnevi, Müge; Özuysal, Mustafa; Özçivici, Engin; Tekin, Hüseyin CumhurBiomechanical changes at cellular level can dramatically affect living organisms in both aviation and space applications. Weightlessness induces morphological alteration of cells, which leads to tissue loss. Therefore, scientists have been studying the effect of weightlessness using cell culture based biological experiments using conventional microscopes. However, strict requirements regarding cost, weight and functionality limit the use of conventional microscopes in space environment. Lensless digital in-line holographic microscopy enables to use low-weight, low-cost and robust elements, such as a light emitting diode (LED), an aperture and an imaging sensor, instead of bulky, expensive and fragile optical elements, such as lenses, mirrors and filters. This technology offers a high field of view compared to conventional microscopes without affecting the resolution and it is also suitable for remote sensing applications with automated imaging capabilities. Here, we present a portable digital in-line holographic microscopy platform that allows to visualize cells and to analyze their viability in a microfluidic chip. The platform offers microscopic imaging with 1.55 mu m spatial resolution, 21.7 mm(2) field of view and image coloring capability. This platform could potentially play an important role in space biotechnology applications by enabling low-cost, high-resolution and portable monitoring of cells.
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