## 3 Stimuli-Responsive Mechanisms: Avenues for 4D (Bio-)printing
### Magnetically Responsive Materials  
Polymers that respond to the presence or absence of magnetic fields may exist as free strands in solution, or may be framed on surfaces or be crosslinked inside polymer networks. Typically, inorganic magnetic particles called \"nancos\" are covalently immobilized on 3D lattices, causing the materials to have a change in shape and size, the latter occurring instantaneously in the presence of a nonuniform magnetic field, which makes the process reversible. In this case, the stimulation imparted to the polymers results in a magnetic susceptibility, leading to a great interest in such materials for their use as soft biomimetic actuators, sensors, cancer therapy agents, artificial muscles, separation media, membranes, and drug delivery systems [41, 105, 106]. During the printing process, a magnetic field is applied to control the orientation of printed anisotropic particles containing rigid magnetized plates. The composition of biomaterials can be controlled by using only a two-component unit or more materials to form a single geometry, thereby adding an extra dimension to the available design space, and ultimately allowing the fabrication of functional constructs that can mimic the intricate biological constructs in nature [24]. Magnetic hydrogels are a combination of hydrogel systems with magnetic nanoparticles (MNP). MNPs, such as cobalt ferrite (CoFe\({}_{2}\)O\({}_{4}\)), iron platinum (FePt), iron (III) oxide (Fe\({}_{2}\)O\({}_{3}\)), and iron (II, III) oxide (Fe\({}_{3}\)O\({}_{4}\)), respond to magnetic stimuli, ultimately leading to hydrogel deformations [29, 40, 107, 108]. Some reports describe a combination of magnetic Fe\({}_{3}\)O\({}_{4}\) particles with different polymers as semiconductors or active scaffolds used for on-demand drug and cell delivery [105, 106, 109, 110, 111, 112]. In another attempt, iron nanoparticles/[11-(2-bromo-2-methyl)-propionyloxy]undecyltrichlorosilane (Fenp-PS gel) was used for cancer therapy [113]. The toxicity of cobalt ferrite is dose dependent; i.e.,  
Figure 5: Immunofluorescence images of anti-Tuj1 (red) and anti-GFAP (green) followed by DAPI (blue) staining for the nuclei of the fetal NSCs on crosslinked PEDOT:PSS. NSCs differentiation occurred on crosslinked PEDOT:PSS substrates without (**a**) and with (**b**) electric stimulation. (**c**) Quantification of aspect ratio of neurons. More than 30 cells were analyzed. (**d**) Quantification of percentage Tuj1 positive. \({}^{*}\)\(p<0.05\). Reprinted with permission [101] © 2020 Elsevier. low quantities induce no interference with cell viability, whereas high quantities lead to a significant decrease of the viability [96]. There are several studies that indicate the level of toxicity of FePt but it highly depends on the surface coating, the concentration, the Fe precursor, and the cell lines used. In some cases, it has been shown that the level of toxicity is low with no relevant effect on cell viability [96]. To detect the toxicity of iron oxide, several studies have been carried out, which, however, have brought discordant results. They indicate that the size of the particle and the surface coatings are crucial for the effects induced by iron oxide since they determine the intensity of the effects and the potential mechanisms of cellular toxicity [114]. Magnetism is widely used in the biomedical field, for instance, to control the release of drugs [24], as ferrogels respond to magnetic stimuli. These ferrogels lie in the nanometer scale, which may limit the transport of large molecules and cells through the gels. To create greater cell adhesion and to produce the release of large molecules, magnetic scaffolds have been produced with larger pores connected three-dimensionally and coupled with magnetic nanoparticles and cell-binding peptides (Figure 6) [112].