## 3 Stimuli-Responsive Mechanisms: Avenues for 4D (Bio-)printing
### Humidity-Responsive Materials
Polymers with shape memory induced by water have received relevant consideration. [PERSON] et al. [49] developed polymers presenting promising potential for biomedical actuation, such as self-tightening sutures, or self-retractable and removable stents. They developed a synthetic network of polymer nanocomposites capable of responding to water stimulation through the chemical crosslinking of cellulose nanocrystals (CNC) with poly(\(\epsilon\)-caprolactone) (PCL) and (PEG). In particular, the PEG [60]-PCL [40]-CNC [10] nanocomposite was found to have excellent water-induced shape-memory effects at 37 \({}^{\circ}\)C (Figure 3a). Both PCL and PEG can be applied in medicine since they are biocompatible and biodegradable materials making them good candidates for applications as biomaterials, as already mentioned in the literature and approved by the U.S. Food and Drug Administration [61]. Less is known on CNC biocompatibility, as their use for biomedical purposes is recent. However, cytotoxicity tests have confirmed that nanocomposites have very good cytocompatibility, suggesting that they can be used in biomedical applications such as vascular stents, esophageal stents, smart sutures, tissue engineering scaffolds, and drug delivery [49]. PEG and PEG-diacrylate hydrogel are also able to respond to water stimulation and have been used as sensors and actuators, or in the construction of soft robots, artificial muscles, programmable origami, energy generators, and scaffolds for TE applications [51; 52; 53; 62]. Figure 3b shows the effects of different exposure times on the humidity response sensitivity of the PEG-DA hydrogel films. By increasing the variation of relative humidity (\(\Delta\)RH), the bending curvature  
Figure 3: Humidity-responsive of smart materials: (**a**) Water-responsive shape-memory process of the PEG–PCL–CNC nanocomposites in water at 37 \({}^{\circ}\)C. Reprinted with permission [49] © 2020 American Chemical Society. (**b**) Dependent curve of bending curvature on the variation of relative humidity (\(\Delta\)RH) for PEG-DA hydrogel films with different exposure time. Reprinted with permission [52] © 2020 John Wiley and Sons. (**c**) Locomotion of a PEE-PPy film on a moist substrate. One flipping cycle refers to a motion process starting from stage I through stage V and back to stage I. Reprinted with permission [54] © 2020 The American Association for the Advancement of Science. (**d**) Biomimetic dragonflies with moisture response fabricated by PEDOT: PSS/PVDF composite film. Reprinted with permission [56] © 2020 Elsevier. of the three films increased. Longer exposure time also led to an increased crosslinking density of the polymer networks, therefore under the same \(\Delta\)RH, the film with longer exposure time had a smaller bending curvature [52]. Active origami are self-actuating structures, which are capable of folding and unfolding. By designing structures that can fold and occupy small spaces, origami can potentially provide suitable solutions for minimally invasive surgery. Another type of moisture-sensitive actuators is based on liquid-crystalline (LC) polymer networks. These have the ability to provide intricate anisotropic deformations, such as spiral ribbons, helicoids, and conic and anticonic forms. Usually, the control of the aimed deformations is based on the alignment and molecular order of the LC units, throughout the three dimensions of the polymer network [47]. Likewise, these networks activated with an alkaline solution can be used as humidity-responsive actuators for application in smart textiles. As a recent example, elastomeric, soft, water-swelling, shape-memory liquid-crystalline anisotropic hydrogels have been proposed as a novel biomaterial [50]. Some other compositions have been used as humidity-sensitive materials for different applications [54; 56; 57; 58; 59; 63]; for example, the pentaerythritol ethoxylate-polypyrrole (PEE-PPy) film folded into a roll and remained static in a closed chamber saturated by water vapor.