## 3 Stimuli-Responsive Mechanisms: Avenues for 4D (Bio-)printing
### Humidity-Responsive Materials  
As water abundant in nature, humidity-sensitive polymers are receiving much consideration in the health and personal comfort domains, as well as for many industrial and technological applications [47]. In the TE field, the humidity-responsiveness is the property that refers to different levels of temporal/spatial swelling deformation that can be induced in a scaffold [24]. However, they are still practical challenges for extensive use of such materials due to their responsive times together with complicated control actuation, mostly provoked by the slow kinetics of water diffusion. Table 1 reports examples of 4D smart material in this field. One controversial material, due to carcinogenic properties, is based on poly(ethylene glycol) (PEG)--combining azobenzene derivative (PCAD) with agarose (AG), forming PCAD@AG [16; 48]. As azobenzene is classified as B2 (probable human carcinogen) according to the National Centre for Environmental Assessment, this material is likely not to be adequate for humans, even if there is no carcinogenicity data in humans [60]. Indeed, when studied in both genders of mice, azobenzene (dietary administration) had negative effects inducing invasive sarcomas in the spleen and in other abdominal organs afterward. In addition, it is genotoxic and under acidic conditions in the human stomach it may be converted to benzidine [32]. Either way, researchers have been studying its properties as agarose (fast water absorption material but low desorption) combined with PCAD can decrease the absorption rate and increase desorption, establishing a moisture responsive system [16]. When the PCAD@AG film is in contact with moisture, it quickly absorbs water and swells, folding up. This folding can be guided with a moisture gradient; PCAD@AG folds or coils according to the expansion on the contact \begin{table}
\begin{tabular}{c c c c} \hline \hline
**Material(s)** & **Mechanism(s)** & **Application(s)** & **Ref.** \\ \hline PEG–PCAD@AG & Humidity & For applications that require contactless actuation in response to the day–night rhythm of atmospheric humidity & [48] \\ \hline PEG–PCL–CNC & Humidity & Medical applications such as smart sutures, vascular stents, esophageal stents, tissue engineering scaffolds, and drug delivery & [49] \\ \hline Liquid–crystalline (LC) polymer networks activated with an alkaline solution & Humidity & Humidity–responsive actuators for application in smart textiles & [47; 50] \\ \hline Poly(ethylene glycol) diacrylate hydrogel & Humidity & Sensors, actuators, or construction of soft robots, artificial muscles, molecular motors, programmable origami, and energy generators & [51; 52] \\ \hline Polyethylene glycol & Humidity & Tissue engineering & [53] \\ \hline Combining polypyrrole and polyol-borate & Humidity & Actuator and generator & [54] \\ \hline Cellulose stearoyl esters (CSEs) & Humidity, temperature & Sensors, actuators, or construction of soft robots & [55] \\ \hline Poly(3,4-ethylenedioxythiophene): polystyrene sulfonate and poly(vinylidene fluoride) & Humidity & Actuator and generator & [56] \\ \hline PEDOT:PSS/PVDF composite & & & \\ \hline Printing a layer of hydrophilic material over a layer of rigid material & Humidity & Self-evolving structure & [57] \\ \hline Hydrogel composite ink composed of stiff cellulose fibrils embedded in a soft acrylamide matrix & Humidity & Tissue engineering, biomedical devices, soft robotics & [58] \\ \hline Poly(ionic liquid)s (PILs), poly(1-methyl azobenzene-3-vinylimidazolium bromide) ([PMAzoVIm]Br) and poly(acrylic acid) (PAA) & Humidity and light & Selective dye adsorption & [59] \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Overview of the experiments on 4D (bio-)printing and other manufacturing approaches using humidity as a predefined stimulus. side produced by the water absorption. In contrast, if placed on a wet filter paper, its membrane will rapidly coil and unwind in successive reverse directions, rapidly moving on the paper [48].