**Abstract**

Hydrogels are a promising type of soft material featuring great similarity to biological tissues due to their inherent characteristics, such as high-water content, flexibility, softness, or low elastic modulus. Imparting multifunctionality to hydrogels to be triggered by external stimuli is considered to have a high potential for innovative application in the biomedical field by regulatory agencies, such as FDA and EMA. Thus, functional hybrid systems based on the combination of nanomaterials and hydrogels are a new class of materials offering new opportunities for living organisms-machine interfacing for application in a wide variety of fields ranging from biomedical engineering to soft robotics, soft electronics, environmental or energy science. The objective of this chapter is to review the latest advances in multifunctional hybrid hydrogels with responsiveness to electric and magnetic fields and with applications in the biomedical field.

**Keywords:** hydrogels, nanomaterials, hybrid composites, stimuli-responsive, electric and magnetic field

### **1. Introduction**

Human body is a complex system where multiple processes and reactions take place simultaneously to give an efficient system. A lot of functions in the body are regulated by chemical substances (e.g., proteins) but also by physical (e.g., electric fields, temperature, light, etc.) and mechanical stimuli, such as neuronal communication, embryo development, tissue repair after an injury, or heartbeat [1–3]. Scientists and engineers have been inspired by the natural world in general, but in the human body in particular, to develop materials with new functionalities and unique skills [4, 5]. Recently, hydrogels have been revealed as a promising new class of materials due to their intrinsic properties, such as high-water contents, high porosity, flexibility, or biocompatibility, showing great similarities to biological systems as a result of the 3D porous polymeric structure [6, 7]. Hydrogel flexibility and elasticity are important to diminish the mechanical mismatch with living systems; meanwhile, the high-water contents provide a humid environment rich in ions, such as biological media. Hydrogels also show some other interesting properties, such as self-healing

and self-adhesive capacity, biocompatibility, and biodegradability [8, 9]. For all those reasons, hydrogels have been suitable for different biomedical applications, such as wound healing [10], passive drug delivery [11], or contact lenses [12]. However, one of the main drawbacks of hydrogels is the lack of bioactivity.

To overcome hydrogel's inertness, hydrogels can be successfully modified with nanomaterials (e.g., metallic nanoparticles and carbon nanomaterials) to develop smart nanocomposite hydrogels with improved functionality [13–15]. Thus, nanomaterials can improve the mechanical properties of the nanocomposite hydrogels (e.g., stiffness, toughness, and ductility) but also confer physical properties (e.g., electrical conductivity, magnetism, thermal properties, etc.) to be able to respond to different stimuli, such as electric and magnetic fields, temperature, pH, light or biomolecules, among others. Hydrogel's response is based on phase changes, change in stiffness, or change in volume in response to those stimuli [16]. These nanocomposite hydrogels, named as smart, intelligent, or stimuli-responsive, are being applied in a wide range of applications including bioelectronic devices (e.g., biosensors) [17, 18], energy and environmental science [19, 20], soft robotics [21, 22], or regenerative medicine [23, 24], with promising advances in all those fields. Moreover, these stimuli-responsive hydrogels show the capacity to respond in a reversible and controllable way to different stimuli but also to adapt and conform onto curvilinear and dynamic surfaces improving their performance [25].

Due to the different length scales and physicochemical properties of the two main components of the stimuli-responsive composites—hydrogels, nanomaterials-, hybrid hydrogels with variable and tunable designs are being possible. Hydrogels have similar mechanical properties to biological tissues and they also mimic several features of the extracellular matrix. They also have compliant and permeable structures that can be modified to suit the requirements to create not just a physical but also a chemically favorable environment [6, 7]. To obtain the characteristic three-dimensional hydrogel networks, with the abovementioned innate properties making them very interesting in comparison to other polymer groups, it is required to transform the liquid viscous precursor solution to the final gelled material by inducing crosslinking. The liquid-gel transition can be achieved either via physical (e.g., ionic crosslinking) or chemical (e.g., photo-crosslinking), leading to the formation of non-covalent and covalent hydrogels, respectively. Moreover, hydrogels can be classified as natural and synthetic depending on the source used to fabricate them [26]. Natural polymers have high interest due to their inherent biocompatibility, low toxicity, and biodegradability. There are two main types, polysaccharides and fibrous proteins that are both components of the extracellular matrix, such as alginate (Alg), chitosan (CS), or collagen (Col), among others. Synthetic polymers, such as poly(ethylene glycol) (PEG), poly-(N-isopropylacrylamide) (PNIPAAM), poly(vinyl alcohol) (PVA), or poly(hydroxyethyl methacrylate) (PHEMA), have controllable and good mechanical properties but they lack bioactivity to promote cell-material interaction, the reason why they are required to be modified. On the other hand, the nanometric size of nanomaterials (<100 nm at least in one dimension) confers them higher specific surface areas compared to their bulk counterparts and very unique physical properties as they are size-dependent, such as the electronic, magnetic, and optical properties, due to the quantum size effect [27]. Nanomaterials are very versatile since they can be synthesized using different materials (e.g., metals and metal oxides, carbons, polymers, etc.), sizes (e.g., 0–100 nm), and shapes (e.g., nanoparticles, nanowires, nanotubes, 2D layers, etc.) and can be modified by combining different materials (e.g., core-shell structures)

#### *Hybrid Hydrogels with Stimuli-Responsive Properties to Electric and Magnetic Fields DOI: http://dx.doi.org/10.5772/intechopen.102436*

or functionalized with biomolecules (e.g., peptides, enzymes) [28]. However, some requirements are needed for their application in the biomedical field, such as biocompatibility, non-cytotoxicity, and stability in biological media [29].

Stimuli-responsive hydrogels are able to respond to different stimuli that can be classified as endogenous—pH, enzymes, antigen—or exogenous—light, electric field, magnetic field—depending on if they are present at the implantation site or not, respectively. However, the most common form of classification is as chemical or physical stimuli if the changes in the hydrogels are induced by chemical entities (e.g., molecules and biomolecules) or physical variables (e.g., temperature, light, electricity, etc.). Chemical stimuli include molecules and biomolecules present in the environment where the hydrogel will be located. For example, reactive oxygen species (ROS) are generated in wounds, bacterial infections, or tumors creating a more oxidation environment. Or pH values are lower in cancerous cells than in normal cells due to abnormal metabolism. Thus, chemically responsive hydrogels must be designed to respond to changes in those (bio)molecules that sometimes are very low, making the development more difficult. Meanwhile, physical stimuli include magnetic and electric fields, temperature, light, or ultrasounds. Among them, electrically- and magnetic-responsive hydrogels have been widely researched as they have the advantage to be remotely and non-invasively operated even in narrow and small areas. Moreover, the use of adjustable electric (e.g., voltage) or magnetic (e.g., field intensity) signals as stimulation sources make them even more interesting to develop hydrogels with reversibility and controllability compared with, for example, pH or temperature-responsive hydrogels. Thus, stimuli-responsive scaffolds capable of responding to either electric or magnetic fields have emerged as a promising technology for biomedical applications, including drug delivery systems, tissue regeneration, or soft actuation. For this reason, in this chapter, the author will focus on electricallyand magnetic-responsive hydrogels.

### **2. Electrically-responsive hydrogels**

Electroresponsive hydrogels have been the most studied among the physically stimuli-responsive hydrogels due to their broad applicability in many fields, such as bioelectronics (e.g., sensors), bioengineering (e.g., drug delivery systems and actuators), tissue engineering (e.g., bone regeneration), or soft robotics applications. They are able to undergo changes in their shape and size when swell/deswell under the application of an electric field. Very briefly, the deformation generated by the electric field can be explained by a combination of Coulombic, electrophoretic, and electroosmotic interactions. As a result of the migration of mobile ions from the electrolyte under the applied field, the generated osmotic pressure increases or decreases causing hydrogel swelling or deswelling, respectively [30, 31]. Electrical conductivity has been conferred to the hydrogel mainly following two approaches—(i) The incorporation of conductive nanofillers, and (ii) the preparation of intrinsic conductive hydrogel networks. Multiple electroconductive fillers have been tested, such as metallic nanomaterials (e.g., nanoparticles (NP), nanorods (NR), and nanowires (NW)), made of noble metals, such as Au, Ag or Pt, carbon nanomaterials (e.g., carbon nanotubes (CNT) and graphene) or conducting polymers (CP) (e.g., polypyrrole (PPy), polyaniline (PANI), poly(3,4-ethylenedioxyhiophene) (PEDOT)) [32, 33]. Any of those materials can confer, apart from electrical conductivity, many other properties to develop multifunctional hydrogels. More recently, preparing inherently

conductive hydrogels using pure CP or blends with other synthetic/natural polymers has been outstanding [34, 35].

Regarding the first strategy, electrically conductive nanomaterials have been successfully employed to develop electrically-responsive hydrogels. Different hydrogel matrices either natural, Alg, CS, and Col, or synthetic, PVA, PEG, and PNIPAAM, have been used to incorporate the conductive fillers [32, 33]. These conductive nanomaterials that are nanometer-sized particles show different properties (e.g., electrical, optical, etc.) depending on the size, shape, and type of material that make them very useful to tailor hydrogel properties. Among the conductive fillers, metal nanomaterials in general, but Au and Ag in particular, have been by far the most employed. Gold shows excellent electrical, optical, and catalytic properties together with biocompatibility, ease of functionalization, and resistance to oxidation; meanwhile, silver has a unique electrical, optical, chemical, and antibacterial properties to develop multifunctional hydrogels. On the other hand, carbon nanomaterials, especially CNT and graphene, are also excellent conductive materials to incorporate into non-conductive hydrogels. Properties, such as high electrical conductivity, high strength, high specific surface area, or low density, have conferred them very interesting applicability within the biomedical field.

Regarding the second strategy, CP have been essential in the development of intrinsic conductive hydrogels. CP are conjugated polymer materials showing electronic conductivity due to the free motion of the delocalized π-electrons throughout the double bonds and aromatic rings present in the polymeric chain originating electrical pathways for charge carriers' motion. The π-orbitals of these conjugated systems are overlapped along the chain that allows the delocalization of the electrons throughout the macromolecule's backbone [36]. The most employed CP for conductive hydrogels has been PANI, PPy, and PEDOT due to properties, such as high conductivity, high stability, biocompatibility, or water dispersibility [37]. However, their main drawback is their fragility and low mechanical strength. For this reason, CP have been mixed with other non-conductive natural and/or synthetic polymers to form interpenetrated (IPN) or semi-interpenetrated hydrogels (s-IPN) to improve the mechanical properties [38]. The addition of electrically conductive nanomaterials into the blended hydrogels has also been done to overcome the decrease in electrical conductivity attributed to the presence of the non-conductive polymer.

Researchers have employed different methodologies to develop electrically conductive hydrogels—(i) blending, (ii) in situ formation, and (iii) covalent bonding (**Figure 1**). Blending has been one of the most used approaches to develop such hybrid hydrogels due to its simplicity and the wide range of nanomaterials that can be incorporated into the hydrogel. This method consists of mixing the hydrogel precursors with the colloidal NP suspension followed by crosslinking to entrap the NP within the hydrogel network. For example, Baei and collaborators fabricated a AuNP-chitosan (AuNP-CS) hydrogel for cardiac tissue engineering. Gold NP with a diameter of 7 nm were embedded in the hydrogel precursor solution by chemically reducing the tetrachloroauric acid (HAuCl4) with sodium citrate followed by chitosan crosslinking with β-glycerophosphate. The presence of the NP slightly increases the compressive modulus from 6.1 kPa for the bare chitosan to 6.9 kPa for the AuNP-CS hydrogel. Moreover, they observed that the presence of the NP conferred electrical conductivity to CS in a value close to the native myocardium (0.13 S/m). The sole presence of the NP allowed detecting an increase in the cardiac differentiation-related markers (e.g., Nkx-2.5 and α-MHC) of the mesenchymal stem cells (MSC) seeded on the scaffold [43]. Navaei et al. successfully incorporated Au NRs into gelatine-methacrylate solution that after

*Hybrid Hydrogels with Stimuli-Responsive Properties to Electric and Magnetic Fields DOI: http://dx.doi.org/10.5772/intechopen.102436*

#### **Figure 1.**

*(a) (I) Photograph of PVA/PEG hydrogel (top) and PVA/PEG/GO (bottom). (II) SEM image of the PVA/PEG/ GO hydrogel cross-section. Reproduced with permission from Ref. [39]. (b) (I) SEM image of the PEDOT/Alg hydrogel cross-section. (II) Transmission electron microscopy (TEM) micrographs with different magnifications (from low at the left to high at the right and bottom) of a stained PEDOT/Alg hydrogel. Adapted with permission from Ref. [40]. Copyright (2020) American Chemical Society. (c) (I) SEM image of the PPy/PAM/ CS hydrogel and (II) magnified SEM image showing the PPY NR embedded in the hydrogel. (III) Variation of the tensile modulus of PPy/PAM/CS hydrogels with various contents of CS. Adapted with permission from Ref. [41]. Copyright (2018) American Chemical Society. (d) (I) Scheme of the hydrogel showing the covalent crosslinking between the CS and PEG. SEM images of hydrogels (II) before and (III) after swelling. Scale bar: 300 μm. Adapted with permission from Ref. [42]. Copyright (2016) American Chemical Society.*

UV-crosslinking led to hydrogels with improved properties for cardiac regeneration. The incorporation of Au NRs (16 ± 2 nm width and 53 ± 4 nm length) led to an increase in the mechanical and electrical properties compared to the pure hydrogel. This hydrogel induced excellent cell retention and proliferation resulting in the formation of cardiac tissue layers with beating behavior [44]. Carbon nanomaterials—CNT, graphene oxide (GO)—have also been widely explored in electrically conductive hybrid

hydrogels. Xiao and collaborators prepared a PVA/PEG/GO hybrid hydrogel with high electrical conductivity and mechanical strength (**Figure 1A**). First, PVA and PEG were dissolved in water at 90°C and cooled to room temperature. After that, GO was dispersed in water, subsequently added to the PVA-PEG solution and mixed until obtaining a homogeneous distribution of GO. Finally, the crosslinking was obtained by the cyclic freezing-thawing method [39]. The blending method has also been employed to develop hybrid hydrogels between CP and insulating polymers either natural or synthetic to confer mechanical properties to the blended hydrogel. It is important to highlight that the electrical performance is normally directly proportional to the content of CP. For example, A. Puiggalí-Jou et al. fabricated an electrochemically active blended hydrogel between PEDOT and alginate biopolymer by an easy one-step process. After thoroughly mixing an aqueous PEDOT:PSS (poly(styrene sulfonate)) dispersion with a fixed amount of an Alg solution, the mixture was placed in a mold and immersed in a CaCl2 solution to crosslink Alg. As observed by the authors, both polymers showed high porosity and they were organized as segregated PEDOT- and Alg-rich regions (**Figure 1B**). The incorporation of curcumin as a model hydrophobic drug allowed demonstrating that the application of a negative potential allowed controlling its release [40]. Gan et al. prepared an IPN based on CS and polyacrylamide (PAM) by UV photopolymerization [41]. First, CS was dissolved in deionized water followed by the addition of given amounts of the monomer (acrylamide (AM)), the crosslinking agent (e.g., N,N′-methylene bisacrylamide) (MBAM), and the initiator (e.g., ammonium persulfate (APS)). The mixture was crosslinked under UV irradiation for 5 min. The resultant hydrogel also showed high porosity to allow its further modification with PPy NWs. Generally, two main drawbacks have been found with the blending methodology—(i) aggregation of the conductive nanomaterials or phase separation between insulating and CP leading to heterogeneous properties across the hydrogel limiting its electrical conductivity and weakening its mechanical strength and (ii) weak nanomaterial-polymer or CP-insulating polymer interaction hindering the full exploitation of nanomaterials or CP. Therefore, the surfactants, polymer-stabilized dispersions, or functionalized nanomaterials are required to properly disperse, and therefore, process them into homogeneous hybrid hydrogels hindering, in most cases, their electrical properties [45].

An alternative methodology to synthesize the conductive hybrid hydrogels avoiding aggregation is the in situ formation of the conductive material within the hydrogel to improve their interaction and therefore integration. Although this approach is dependent on the type of conductive material, generally is based on homogeneously mixing both the conductive (nano)material and the hydrogel precursors followed by the formation of the (nano)materials and crosslinking of the hydrogel. More specifically, metallic nanomaterials can be incorporated by in situ process by mixing the metal ions with the hydrogel precursors. One important point is achieving a homogeneous dispersion of ions before the metallic NPs are grown in the hydrogel. For example, Dolya and colleagues have reported the in situ formation of Au NP within PAM hydrogels following a one-step process. This step consisted of dissolving AM, MBAAM, and APS involved in the hydrogel formation together with HAuCl4, poly(ethyleneimine) (PEI), and the ionic liquid (IL) ethyl-3-methylimidazolium ethylsulfate as a gold precursor, reducing and stabilizing agent, respectively. The formation of the hydrogel and Au NP took place simultaneously by heating the solution at 80°C for 30 min. Results show that hydrogels have high porosity and Au NP are better dispersed and stabilized within the hydrogel when PEI and IL form a shell around the NP preventing their aggregation. While the lack of aggregation was

#### *Hybrid Hydrogels with Stimuli-Responsive Properties to Electric and Magnetic Fields DOI: http://dx.doi.org/10.5772/intechopen.102436*

observed by UV-Vis spectroscopy, better immobilization was detected through kinetic studies of the release of unbound charged compounds [46]. Au NP have been successfully synthesized within many natural (e.g., pectin and κ-carrageenan) and synthetic (e.g., poly(N-vinylpyrrolidone) (PVP), PEG, etc.) hydrogels following the in situ method [47]. Incorporation of CP inside a hydrogel can also be achieved by in situ polymerization. First, CP monomers are incorporated either with hydrogel precursors or after crosslinking by immersing it into the monomer solution and followed by introducing the oxidative reagents (e.g., APS, ferric ions, etc.) to initiate the polymerization. Thus, Gan et al. incorporated PPy NW inside a PAM/CS hydrogel by first immersing the template hydrogel into a pyrrole (Py) solution and second adding the ferric chloride as oxidation agent. The PPy NW, clearly observed by scanning electron microscopy (SEM), enhanced the mechanical properties of the PAM/CS hydrogel (**Figure 1C**) [41]. Or Hur and coworkers reported the fabrication of an interpenetrated network of agarose and PPy by pyrrole polymerization within the agarose gel. First, the authors mixed an agarose aqueous solution with CuCl2 as an oxidizing agent at 40°C. After that, they added a pyrrole monomer to initiate polymerization within the solution. The temperature was decreased down to room temperature to induce agarose gelation, while PPy formation still took place. The addition of the monomer helped to get a homogeneous distribution between agarose and PPy. They developed an electrically conductive hydrogel with self-healing and stretchability [48]. Wu et al. showed the preparation of a conductive hydrogel composed of gelatin methacrylate (GelMA) and PANI. First, GelMA was prepared by UV photopolymerization using irgacure 2959 as initiator. After that, the hydrogel was immersed first in an HCl and APS solution for 4 h followed by immersion in a hexane solution containing the aniline monomer for another 4 h for the polymerization to take place. No significant differences in terms of mechanical properties, swelling, and cell adhesion were observed between the bare GelMA and the GelMA/PANI hydrogel except for an increase in the electrical conductivity of the latter [49]. In situ polymerization can also be achieved by electropolymerization in which an electrical potential or current plays the role of an oxidative reagent inducing polymerization within the template hydrogel [50].

Finally, another strategy to improve even more the interaction between the hybrid hydrogel components (e.g., nanomaterials and polymers), which is normally weak if the previous strategies are used, is through covalent bonding. Here, a covalent bond is formed between the different materials to, for example, stabilize the NP inside the hydrogel but also to boost the chemical and biological properties of the hybrid hydrogel. Skardal et al. synthesize hyaluronic acid (HA), gelatin, and Au NP hydrogels using non-functionalized and thiol-functionalized NP. What they observed is a significant increase in the hydrogel stiffness when the functionalized NP were used, which they attributed to the covalent bond formed with the hydrogel matrix [51]. This methodology has also been explored with carbon nanomaterials. For example, poly(acrylic acid) (PAA) has been grafted onto CNT surface for the promotion of neuron differentiation. First, the authors treated CNT with 4 M nitric acid by reflux to increase surface hydrophilicity. After that, those CNT were dispersed by sonication for 30 min in an acrylic acid-acetone solution followed by the addition of 2′-azobisisobutyronitrile (AIBN) to obtain the PAA. They successfully induced selective differentiation of MSC into neurons [52]. Dong et al. created a covalent bond between a chitosan-graft-aniline tetramer (CS/AT) and a dibenzaldehyde-terminated poly(ethylene glycol) (PEG/DA) to obtain a covalent IPN that they used as drug delivery for cardiac regeneration (**Figure 1D**) [42].

#### **2.1 Biomedical applications**

One of the main applications of hybrid hydrogels with electrical conductivity is in the tissue engineering field where hydrogels aim to restore the electrical/electrochemical intercommunication between cells and tissues. These hybrid hydrogel scaffolds have been developing for many tissues especially electroactive ones, such as cardiac, nerve, skeletal muscle, bone, or cartilage. Baei et al. developed a Au NP/CS hydrogel for cardiac tissue engineering. The authors seeded MSC onto the hydrogels, and although they did not observe any significant difference in cell density, morphology, and distribution between bare chitosan and Au NP/CS hydrogels they did observe higher levels of cardiac markers, such as alpha myosin heavy chain (α-MHC) and homeobox protein Nkx-2.5, indicating that the presence of Au NPs electrically stimulating the differentiation of MSC into cardiac cells (**Figure 2A**) [43]. Gan et al. also developed an electrically conductive hydrogel based on PAM, CS, and different amounts of PPy NR as previously explained for skin regeneration. After seeding the scaffolds with muscle myoblasts, the authors analyzed their morphology, adhesion, and proliferation under different electrostimulation voltages (0–900 mV). They found out that not only the incorporation of PPy NR had a clear effect on proliferation and elongation (e.g., 20 v/v% PPy NR led to the highest cell aspect ratio) but also the application of an electric voltage promoted cell activity and elongation (e.g., 300 mV showed the highest elongation) (**Figure 2A**) [41].

Drug delivery has also been widely studied due to the possibility to control the release of the drug out of the conductive hydrogels by the application of different electrical signals (e.g, voltage). A. Puiggalí-Jou et al. fabricated Alg/PEDOT hydrogels incorporating curcumin (CUR) as a hydrophobic model drug during the hydrogel fabrication process. Interestingly, the authors showed a different release profile depending on the applied voltage (0, +1 V, −1 V). Thus, they observed a higher release when −1 V was applied during 2 h to the hydrogel (e.g., ~25%) compared to the 0 V (e.g., ~3%) or + 1 V (e.g., ~8%), indicating a controlled release of curcumin (**Figure 2B**) [40]. Cho et al. also developed a collagen-CNT hydrogel containing a nerve growth factor (NGF). First, a solution containing the collagen and the NGF was prepared followed by mixing with a COOH-functionalized CNT suspension. Then, the mixture was poured into a mold and heated to induce crosslinking. The hydrogels were electrically stimulated immersing them in PBS solution at 37°C and by applying a voltage of 0.5 V for 2 h per day. The application of the voltage led to an increase in the NGF release during the same period of time. Thus, the 5% collagen hydrogel led to a 10-fold increase compared to the non-stimulated one. Moreover, collagen content in the hydrogel had an effect on the drug release observing a higher release in the order 5% > 1% > 0.5% > 20% collagen. The authors attributed the lower release of the 20% collagen hydrogel to the presence of electrical insulating regions limiting the electrical stimulation [54].

Although less studied, these electrically-responsive hydrogels have been also applied for wound healing or as actuators. For example, the hydrogel PAM/CS/PPy was observed to induce skin reparation in *in vivo* experiments with rats. The authors observed that the wound closed with new epithelial tissue and hair in lesser days than with PAM/CS hydrogels. The good results were attributed to the electroactivity of PPy promoting the electrical communication between cells that at the end controls tissue growth (**Figure 2C**) [41]. On the other hand, Yang et al. developed electrically active hydrogels by incorporating GO into a poly(2-acrylamido-2-methylpropanesulfonic acid-co-acrylamide) (AMPS-co-AM) hydrogel to be used as actuator under an

*Hybrid Hydrogels with Stimuli-Responsive Properties to Electric and Magnetic Fields DOI: http://dx.doi.org/10.5772/intechopen.102436*

#### **Figure 2.**

*(a) (I) Fluorescence micrographs of C2C12 cells seeded on PPy/PAM/CS hydrogels and electrostimulated at different electric potentials. (II) Proliferation of cells evaluated by MTT analysis and (III) cell aspect ratio as a function of hydrogel composition and applied voltage. Adapted with permission from Ref. [41]. Copyright (2018) American Chemical Society. (b) Release profile of curcumin from Alg/PEDOT/CUR and Alg/CUR hydrogels by (I) passive diffusion (0 V) and (II) by applying a voltage of −1 V. Adapted with permission from Ref. [40]. Copyright (2020) American Chemical Society. (c) (I) Scheme showing the implantation of hydrogels onto skin defects on rats. (II) Photos of the defects treated with PAM/CS, PAM/CS/PPy, and PAM/CS/PPy loaded with EGF at different time periods. (III) Graph showing the wound closure percentage. Adapted with permission from Ref. [41]. Copyright (2018) American Chemical Society. (d) (I) Optical photographs of the electro-responsive bending behaviors of (I) poly(AMPS-co-AAm) (blank) and (II) rGO/poly(AMPS-co-AAm) hydrogels. Adapted with permission from Ref. [53]. Copyright (2017) American Chemical Society.*

electric field. The preparation of the composite hydrogel, which was performed in a two-step process, allowed a good dispersion of the GO leading to a hybrid hydrogel with improved electrical and mechanical properties. An electric field originated the deformation (e.g., bending) of the hydrogel that was reversible and repeatable when a cyclic electric field was applied showing great potential as a remotely controlled electro-responsive actuator (**Figure 2D**). The authors explained the actuation based on the different osmotic pressure between hydrogel's inside and outside as a consequence of ionic flux created during the application of the electric field [53].
