This technology has been used in a broad range of applications including automotive, aerospace, model production for visualization, design verification, and biomedicine (Casavola et al., 2016). The details of 3D and 4D scaffold preparation techniques and the types of stimuli they respond to are presented in this review.įused deposition modeling (FDM) was developed and patented by Scott Crump in the late 1980s and is one of the most commonly used rapid prototyping techniques. The smart materials used to make the 4D scaffolds respond to a range of stimuli and adapt to the microenvironment by changing their conformation or other properties. Four-dimensional printing is an invasive and robust technique that enables users to design the modeled simple shapes to transform to complex designs over time through a programming phase which is distinctly different than 3D printing (Rastogi and Kandasubramanian, 2019). Thus, besides having the advantages of 3D printing, such as the production of scaffolds with well-defined internal organization, 4D printing benefits from the property of smart materials to closely imitate the dynamic responses of tissues against natural stimuli. Four-dimensional printing is an emerging field in tissue engineering, where the scaffolds are fabricated using smart materials that enable the scaffolds to mimic the dynamic nature of tissues to a very large extent. The main advantage of 3D printing is the production of patient-specific scaffolds. Three-dimensional printing technology overcomes these limitations of conventional scaffold fabrication techniques. In addition, cells are seeded onto these scaffolds after fabrication and may not penetrate the depths of the structure therefore, cells may not be homogeneously distributed within the scaffold. However, it is difficult to obtain pre-determined, well-defined architectures in a controlled manner using these techniques. The conventional production of scaffolds in a sponge or mesh form are achieved by lyophilization, salt leaching, wet spinning and electrospinning. These 3D constructs, with microporous structures, can be produced through a computer controlled, layer-by-layer process. Three-dimensional printing mainly involves the use of 3D software to establish a model the model is imported into slicing software, and a 3D printer is used to print the model (Bhushan and Caspers, 2017). Three-dimensional printing (additive manufacturing) is achieved by adding materials layer by layer to form the final shape and is a valuable tool in the fabrication of biomimetic scaffolds with desired properties and well-controlled spatial chemistry and architecture. The development of tissue specific scaffolds that possess the complex hierarchy of natural tissues remains deficient in tissue engineering applications. 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.
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