![]() 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. This work was supported in part by NSF EAGER grant award #1152550 "Bio-Beams: Functionally Graded Rapid Design & Fabrication", VA contract # VA118-12-C-0040, and the Media Lab Consortium.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. ![]() This work presents and evaluates a series of enabling explorations into the material, time and information dimensions of additive manufacturing: a variable elasticity rapid prototyping platform and an approach towards Digital Anisotropy, a variable impedance prosthetic socket (VTS) as a case study of interfaces between nature and manufacture, CNSilk as an example of on-demand material generation in freeform tensile fabrication, and Material DNA as an exploration into embedded spatio-temporal content variation. Inspired by Nature's ability to generate complex structures and responses to external constraints through adaptation, "4D printing" addresses additive fabrication of artifacts with one or more additional design dimension, such as material variation over distance or direction and response or adaptation over time. In human manufacturing where design must be preconceived and deliberate, static artifacts with no variation of function across directions, distances or time fail to capture many of these dimensions. Inherent across all scales in Nature's material systems are multiple design dimensions, the existences of which are products of both evolution and environment.
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