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      Innovative Human Three-Dimensional Tissue-Engineered Models as an Alternative to Animal Testing

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          Abstract

          Animal testing has long been used in science to study complex biological phenomena that cannot be investigated using two-dimensional cell cultures in plastic dishes. With time, it appeared that more differences could exist between animal models and even more when translated to human patients. Innovative models became essential to develop more accurate knowledge. Tissue engineering provides some of those models, but it mostly relies on the use of prefabricated scaffolds on which cells are seeded. The self-assembly protocol has recently produced organ-specific human-derived three-dimensional models without the need for exogenous material. This strategy will help to achieve the 3R principles.

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          Three-Dimensional in Vitro Cell Culture Models in Drug Discovery and Drug Repositioning

          Drug development is a lengthy and costly process that proceeds through several stages from target identification to lead discovery and optimization, preclinical validation and clinical trials culminating in approval for clinical use. An important step in this process is high-throughput screening (HTS) of small compound libraries for lead identification. Currently, the majority of cell-based HTS is being carried out on cultured cells propagated in two-dimensions (2D) on plastic surfaces optimized for tissue culture. At the same time, compelling evidence suggests that cells cultured in these non-physiological conditions are not representative of cells residing in the complex microenvironment of a tissue. This discrepancy is thought to be a significant contributor to the high failure rate in drug discovery, where only a low percentage of drugs investigated ever make it through the gamut of testing and approval to the market. Thus, three-dimensional (3D) cell culture technologies that more closely resemble in vivo cell environments are now being pursued with intensity as they are expected to accommodate better precision in drug discovery. Here we will review common approaches to 3D culture, discuss the significance of 3D cultures in drug resistance and drug repositioning and address some of the challenges of applying 3D cell cultures to high-throughput drug discovery.
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            Hydrogels as extracellular matrix mimics for 3D cell culture.

            Methods for culturing mammalian cells ex vivo are increasingly needed to study cell and tissue physiology and to grow replacement tissue for regenerative medicine. Two-dimensional culture has been the paradigm for typical in vitro cell culture; however, it has been demonstrated that cells behave more natively when cultured in three-dimensional environments. Permissive, synthetic hydrogels and promoting, natural hydrogels have become popular as three-dimensional cell culture platforms; yet, both of these systems possess limitations. In this perspective, we discuss the use of both synthetic and natural hydrogels as scaffolds for three-dimensional cell culture as well as synthetic hydrogels that incorporate sophisticated biochemical and mechanical cues as mimics of the native extracellular matrix. Ultimately, advances in synthetic-biologic hydrogel hybrids are needed to provide robust platforms for investigating cell physiology and fabricating tissue outside of the organism. (c) 2009 Wiley Periodicals, Inc.
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              Bone tissue engineering using 3D printing

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                Author and article information

                Journal
                Bioengineering (Basel)
                Bioengineering (Basel)
                bioengineering
                Bioengineering
                MDPI
                2306-5354
                17 September 2020
                September 2020
                : 7
                : 3
                : 115
                Affiliations
                [1 ]Faculté de Médecine, Sciences Biomédicales, Université Laval, Québec, QC G1V 0A6, Canada; patrick.bedard.2@ 123456ulaval.ca (P.B.); sara.gauvin.1@ 123456ulaval.ca (S.G.); karel.ferland.1@ 123456ulaval.ca (K.F.)
                [2 ]Centre de Recherche en Organogénèse Expérimentale de l’Université Laval/LOEX, Centre de Recherche du CHU de Québec-Université Laval, Axe Médecine Régénératrice, Québec, QC G1J 1Z4, Canada; christophe.caneparo.1@ 123456ulaval.ca (C.C.); eve.pellerin.1@ 123456ulaval.ca (È.P.); stephane.chabaud@ 123456crchudequebec.ulaval.ca (S.C.)
                [3 ]Département de Chirurgie, Faculté de Médecine, Université Laval, Québec, QC G1V 0A6, Canada
                Author notes
                Author information
                https://orcid.org/0000-0002-0389-667X
                Article
                bioengineering-07-00115
                10.3390/bioengineering7030115
                7552665
                32957528
                79fb523d-e331-462c-a807-0c464c9277ca
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 08 August 2020
                : 15 September 2020
                Categories
                Review

                tissue engineering,scaffold,extracellular matrix,epithelium

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