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In addition, ECM is a dynamic system that transmits biochemical and mechanical signals from the microenvironment into the cells and affects cell behavior. ECM structurally supports and helps the spatial organization of tissues and also serves as the site for cell anchorage. ECM, with various architectural forms and compositions in different tissues, is a complex 3D network consisting of mainly collagen and elastic fibers, which also contain proteoglycans, multiadhesive proteins (e.g., fibronectin, laminin), and glycosaminoglycans (e.g., hyaluronan). The extracellular matrix (ECM) is a crucial component of the cellular microenvironment and forms a complex three-dimensional network ( Marchand et al., 2018).

Tissues are dynamic structures constituted by multiple cell types, an extracellular matrix (ECM) and a variety of signaling molecules. This review presents a comprehensive survey of 3D and 4D printing methods, and the advantage of their use in tissue regeneration over other scaffold production approaches. Furthermore, physical and chemical guidance cues can be printed with these methods to improve the extent and rate of targeted tissue regeneration. 3D and 4D printing techniques have great potential in the production of scaffolds to be applied in tissue engineering, especially in constructing patient specific scaffolds. Use of intelligent materials which change shape or color, produce an electrical current, become bioactive, or perform an intended function in response to an external stimulus, paves the way for the production of dynamic 3D structures, which is now called 4D printing. Three-dimensional printing enables the fabrication of complex forms with high precision, through a layer-by-layer addition of different materials. Three-dimensional (3D) and Four-dimensional (4D) printing emerged as the next generation of fabrication techniques, spanning across various research areas, such as engineering, chemistry, biology, computer science, and materials science. 7Department of Medical Engineering, School of Engineering, Acıbadem Mehmet Ali Aydinlar University, Istanbul, Turkey.6Department of Chemistry, Middle East Technical University, Ankara, Turkey.5Department of Biomedical Engineering, Middle East Technical University, Ankara, Turkey.4Department of Histology and Embryology, School of Medicine, Acıbadem Mehmet Ali Aydinlar University, Istanbul, Turkey.3Department of Biological Sciences, Middle East Technical University, Ankara, Turkey.2Department of Biotechnology, Middle East Technical University, Ankara, Turkey.