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      Is It Time to Start Transitioning From 2D to 3D Cell Culture?

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          Abstract

          Cell culture is an important and necessary process in drug discovery, cancer research, as well as stem cell study. Most cells are currently cultured using two-dimensional (2D) methods but new and improved methods that implement three-dimensional (3D) cell culturing techniques suggest compelling evidence that much more advanced experiments can be performed yielding valuable insights. When performing 3D cell culture experiments, the cell environment can be manipulated to mimic that of a cell in vivo and provide more accurate data about cell-to-cell interactions, tumor characteristics, drug discovery, metabolic profiling, stem cell research, and other types of diseases. Scaffold based techniques such as hydrogel-based support, polymeric hard material-based support, hydrophilic glass fiber, and organoids are employed, and each provide their own advantages and applications. Likewise, there are also scaffold free techniques used such as hanging drop microplates, magnetic levitation, and spheroid microplates with ultra-low attachment coating. 3D cell culture has the potential to provide alternative ways to study organ behavior via the use of organoids and is expected to eventually bridge the gap between 2D cell culture and animal models. The present review compares 2D cell culture to 3D cell culture, provides the details surrounding the different 3D culture techniques, as well as focuses on the present and future applications of 3D cell culture.

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          Most cited references70

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          Electrospinning and Electrospun Nanofibers: Methods, Materials, and Applications

          Electrospinning is a versatile and viable technique for generating ultrathin fibers. Remarkable progress has been made with regard to the development of electrospinning methods and engineering of electrospun nanofibers to suit or enable various applications. We aim to provide a comprehensive overview of electrospinning, including the principle, methods, materials, and applications. We begin with a brief introduction to the early history of electrospinning, followed by discussion of its principle and typical apparatus. We then discuss its renaissance over the past two decades as a powerful technology for the production of nanofibers with diversified compositions, structures, and properties. Afterward, we discuss the applications of electrospun nanofibers, including their use as “smart” mats, filtration membranes, catalytic supports, energy harvesting/conversion/storage components, and photonic and electronic devices, as well as biomedical scaffolds. We highlight the most relevant and recent advances related to the applications of electrospun nanofibers by focusing on the most representative examples. We also offer perspectives on the challenges, opportunities, and new directions for future development. At the end, we discuss approaches to the scale-up production of electrospun nanofibers and briefly discuss various types of commercial products based on electrospun nanofibers that have found widespread use in our everyday life.
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            Hydrogels in pharmaceutical formulations.

            N. Peppas (2000)
            The availability of large molecular weight protein- and peptide-based drugs due to the recent advances in the field of molecular biology has given us new ways to treat a number of diseases. Synthetic hydrogels offer a possibly effective and convenient way to administer these compounds. Hydrogels are hydrophilic, three-dimensional networks, which are able to imbibe large amounts of water or biological fluids, and thus resemble, to a large extent, a biological tissue. They are insoluble due to the presence of chemical (tie-points, junctions) and/or physical crosslinks such as entanglements and crystallites. These materials can be synthesized to respond to a number of physiological stimuli present in the body, such as pH, ionic strength and temperature. The aim of this article is to present a concise review on the applications of hydrogels in the pharmaceutical field, hydrogel characterization and analysis of drug release from such devices.
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              Recent advances in three-dimensional multicellular spheroid culture for biomedical research.

              Many types of mammalian cells can aggregate and differentiate into 3-D multicellular spheroids when cultured in suspension or a nonadhesive environment. Compared to conventional monolayer cultures, multicellular spheroids resemble real tissues better in terms of structural and functional properties. Multicellular spheroids formed by transformed cells are widely used as avascular tumor models for metastasis and invasion research and for therapeutic screening. Many primary or progenitor cells on the other hand, show significantly enhanced viability and functional performance when grown as spheroids. Multicellular spheroids in this aspect are ideal building units for tissue reconstruction. Here we review the current understanding of multicellular spheroid formation mechanisms, their biomedical applications, and recent advances in spheroid culture, manipulation, and analysis techniques.
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                Author and article information

                Contributors
                Journal
                Front Mol Biosci
                Front Mol Biosci
                Front. Mol. Biosci.
                Frontiers in Molecular Biosciences
                Frontiers Media S.A.
                2296-889X
                06 March 2020
                2020
                : 7
                : 33
                Affiliations
                [1] 1Department of Oral Biology and Diagnostic Sciences, Dental College of Georgia, Augusta University , Augusta, GA, United States
                [2] 2Department of Biology, College of Science and Mathematics, Augusta University , Augusta, GA, United States
                [3] 3Georgia Cancer Center, Medical College of Georgia, Augusta University , Augusta, GA, United States
                [4] 4Department of Medical Laboratory, Imaging and Radiologic Sciences, College of Allied Health, Augusta University , Augusta, GA, United States
                [5] 5Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University , Augusta, GA, United States
                Author notes

                Edited by: Megha Agrawal, University of Illinois at Chicago, United States

                Reviewed by: Sachin Kumar Deshmukh, University of South Alabama, United States; Deepak Gurbani, UT Southwestern Medical Center, United States

                *Correspondence: Yong Teng, yteng@ 123456augusta.edu

                This article was submitted to Molecular Diagnostics and Therapeutics, a section of the journal Frontiers in Molecular Biosciences

                Article
                10.3389/fmolb.2020.00033
                7067892
                32211418
                2692533c-ea46-4236-aeee-0873139adac5
                Copyright © 2020 Jensen and Teng.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 21 November 2019
                : 12 February 2020
                Page count
                Figures: 2, Tables: 2, Equations: 0, References: 99, Pages: 15, Words: 0
                Funding
                Funded by: National Institutes of Health 10.13039/100000002
                Award ID: R01DE028351-01A1
                Categories
                Molecular Biosciences
                Review

                3d cell culture,biomedical and drug research,advance and progress,methods and applications,techniques

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