Samille Henriques Pereira
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Denise Soares de Moura Coutinho
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Ana Flávia de Oliveira Gonçalves de Matos
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Willer Ferreira da Silva Junior
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Daniela Leite Fabrino
Two-dimensional cell culture (2D) is the most used technique in studies of mass production of proteins and vaccines; however, this technique is quite limited, since cells lose their phenotypic characteristics when cultured in monolayer. As an alternative, three-dimensional cell culture (3D) allowed cells to be cultured within an environment closer to their natural one, keeping in that way, their physiologic characteristics. When grown in this kind of system, cells form structures called multicellular spheroids, which present in their cores: cellular heterogeneity, microenvironment formation, and different expositions to several factors, such as nutrients and oxygen. This technique has revolutionized researches on drug development and its mechanism of action, since the results obtained in 3D cell culture are more realistic than the ones arisen from 2D cell culture. Recently, there have been developed many 3D cell culture methodologies, however, it misses technology to scale up the biomass growth, which is a great challenge for bioprocess engineers (BE). Therefore, this review aimed to show the technical reality of 3D cell culture and how such professionals can apply their engineering and life science knowledge to improve and develop new technologies that make the use of 3D cell culture feasible and widely used by biotechnological industries.