its innate properties, or in response to external stimuli. Specifically, the SME can be seen in hybrid structures composed of a smart material and static material due to their inhomogeneity and different properties. [9,10] On the other hand, various stimuli, such as light, temperature, and humidity, can cause SMEs when a smart material converts the stimulus/energy into dynamic movement. With a detailed understanding of the properties of smart materials and their responses to stimuli, 4D printing can be utilized to precisely fabricate a "programmed" dimension that transforms and/or recovers its shape in response to stimuli. Many such smart materials have been developed, thus confirming the feasibility of 4D printing (Figure 1a).In this review, the concept of 4D bioprinting and smart materials will be defined by 4D mechanisms of SMEs and stimulus-responsive mechanisms. Then, 4D bioprinting will be categorized according to the types and cases of biomedical smart materials and applications. The current limitations and future aspects will also be discussed.
Four-dimensional Mechanisms: Shape-Morphing EffectsFour-dimensional printing is essentially a 3D printing technique combined with one more dimension, that is, the SME by pre-set stimuli. The SME in 4D printing occurs after printing of the 3D structure, which is printer-independent but still predictable as the effect is programmed beforehand. [11] The types of SME-inducing stimuli will be discussed in the following section. In this section, SMEs will be classified according to the shape recovery ability of the 4D-printed structure. The SME of 4D structures with no shape recovery ability can be classified as one-way SME, while SMEs with shape recovery ability is classified as two-or multi-way SME.
One-Way Shape MorphingOne-way SME refers to a 4D structure that is designed to change its structure once and is not able to recover its original shape by itself. This irreversibility of one-way SME is shown in Figure 1b. [12] One-way SME is distinguished from normal deformations, such as degradation, contraction, and swelling, as the deformation can be designed and predicted, that is, artificially programmed. One-way SME is a relatively simple mechanism compared to two-or multi-way SME.
BioprintingThe development of the three-dimensional (3D) printer has resulted in significant advances in a number of fields, including rapid prototyping and biomedical devices. For 3D structures, the inclusion of dynamic responses to stimuli is added to develop the concept of four-dimensional (4D) printing. Typically, 4D printing is useful for biofabrication by reproducing a stimulus-responsive dynamic environment corresponding to physiological activities. Such a dynamic environment can be precisely designed with an understanding of shape-morphing effects (SMEs), which enables mimicking the functionality or intricate geometry of tissues. Here, 4D bioprinting is investigated for clinical use, for example, in drug delivery systems, tissue engineering, and surgery in vivo. This review presents ...