**2. Magnetic hydrogels (Ferrogels) and their physical properties**

has been an interesting biomaterial used commonly for biotechnological applications [1–3] and drug delivery systems [4–6]. The physically cross-linked hydrogels can be constructed by hydrogen bonds, crystallization, and ionic and protein interactions, whereas the chemically cross-linked hydrogels can be built by complex chemical reaction (aldehydes), high energy radiation, polymerization, and enzymes [1, 7–9]. There is a disadvantage for the hydrogels prepared by the chemically cross-linked agent and gamma irradiation, namely a toxic residue that might be harmful to biological tissue. Therefore, the physically cross-linked hydrogels are more preferable to be applied for biomedical purposes [8]. Basically, hydrogels are sensitive to some environmental variables, such as acidity level (pH), temperature, electromagnetic signal, light, pressure, and other stimuli, so that they can be applied based on the proper environmental condition [10, 11]. A review of a particular number of synthetic hydrogels for

Polyvinyl alcohol (PVA) is a biocompatible, water-soluble, and nontoxic synthetic polymer, which can be prepared to be a flexible material called PVA hydrogel. A physically crosslinked PVA hydrogel can be achieved by freezing-thawing (F-T) cyclic process [14, 15]. The networking gel structure, crystallinity, stability, and viscoelastic properties of the PVA hydrogels have been investigated [16–19]. The properties of PVA hydrogels prepared by F-T process depend on the molecular weight and concentration of the aqueous PVA solution, temperature, time duration, and number of F-T cycle processes [20]. For instance, Li and coworkers have successfully produced a reversible gel using poly(N-isopropyl acrylamide) (PNIPA) and polyacrylamide (PAM), which can be controlled by external stimuli such as

It has been found that cross-linking density and crystallinity of PVA hydrogel influence the overall mechanical properties of a hydrogel. Gupta et al. [22] had studied the effect of PVA concentration on both modulus elasticity and tensile strength of PVA hydrogel. They found that both mechanical properties increased with increasing PVA concentration up to 16% due to a higher degree of crystallinity and developing hydrogen bond interaction in the PVA hydrogel. In contrast, it has also been shown that higher crystallinity of the hydrogel (obtained by increasing PVA concentration) may cause the increase of optical contact angle, indicating the decrease of water affinity [23]. This is one parameter that should be concerned for producing a stable PVA hydrogel. Moreover, it is revealed that the number of cyclic processes in the F-T method affects the degree of cross-linking density. A higher number of repeated cycle results in the decrease in the amount of not incorporated PVA in the networking structure of hydrogel meaning that the polymer chains of PVA are dispersed and unrelated each other [24].

In the tissue engineering, a transparent PVA hydrogel has been successfully developed as soft tissue substitution due to the similar microstructure and mechanical properties to that of the biological cells and organs [25]. PVA-based composite gels have been also intensively studied for wound healing, tissue replacement, and magnetic-controlled drug delivery devices [26–28]. Liu et al. [29] have demonstrated PVA hydrogel produced by the F-T process as one of the potential materials for an artificial blood vessel. Furthermore, the F-T process can be used widely for preparing and storing cell-laden hydrogels with adjustable mechanical

biomedical applications and tissue engineering has been discussed [4, 12, 13].

temperature [21].

160 Hydrogels

properties [30].

The magnetic hydrogel, or so-called ferrogel, is one of the "smart" polymeric composite gels containing micro- or nano-sized magnetic particles as filler in its polymeric matrix. There are some magnetite hydrogels (ferrogels) that have been successfully developed recently, namely PVA-Fe3 O4 -based hydrogel [34], Fe3 O4 -polyacrylamide (PAM) hydrogels [35], and Fe3 O4 -polymethylmethacrylate (PMMA) hydrogels [36]. They have found that those magnetic nanocomposites forming magnetic hydrogels have superparamagnetic behavior due to the presence of dispersed magnetic nanoparticles in the polymeric matrix. The properties of superparamagnetic of magnetic iron oxide nanoparticles itself have been investigated intensively [37]. A simulation study of deformation, elasticity, and magnetic response of magnetic nanoparticles cross-linked in a gel (polymeric matrix) has been conducted [38]. They have found that the degree of networking chains plays an important role in determining the stiffness and magnetosensitivity of the magnetic hydrogels. The sensitivity of magnetic response in the external magnetic field depends strongly on the volume fraction of both magnetic nanoparticles and polymeric base matrix influencing the interacting energy in the ferrogel [28]. They found an optimum magnetosensitivity with Fe<sup>3</sup> O4 and PVA concentration in the range of 17–34% and 10–12.5%, respectively.

Ferrogel is a new type of polymeric matrix composites, in which they are physically (or chemically) cross-linked polymer network containing dispersed magnetic particles. Zrínyi et al. [39] have synthesized ferrogel as a new promising material for magnetic-responsive applications. Ramanujan and Lao [40] and Reséndiz-Hernández et al. [41] have developed composite gels based on PVA and magnetite (Fe3 O4 ) particles by conventional F-T process. Moreover, Hernández et al. [19] have reported the viscoelastic properties of PVA hydrogel and ferrogel prepared by F-T cyclic process. It has been revealed that the reinforcement effect from the magnetic particles, as well as the mechanical properties, of the PVA-Fe3 O4 ferrogels depends on the size, possible agglomeration, and concentration (volume fraction) of the magnetic particles [42]. It has been noted that the concentration of Fe<sup>3</sup> O4 nanoparticles affects the thermal stability of the ferrogels [43]. As for the mechanical properties of the PVA-Fe<sup>3</sup> O4 ferrogels, it has been shown that the deflection and elongation parameters are dependent on the Fe<sup>3</sup> O4 concentration and external magnetic field strength [40] and the deformation is independent on the shape of ferrogels [44]. Experimentally, the magnetodeformation of the ferrogels with highly concentrated particles (approximately above 30%) is due to the effect of short range order and magnetic interaction among the particles [45, 46]. Furthermore, the structural and magnetic behavior of ferrogels has been intensively studied with the dispersed magnetic particle having average size less than 10 nm [47, 48].

was set under gravity force for 5 s, and the depth of penetration was measured in tenths of millimeters. The depth of penetration depended on the kinetic energy applied to the penetrometer and the sample resistance. The resistance data were collected to obtain the consistency value describing the required mechanical force to decelerate from its initial velocity to

 **nanoparticles from iron sand**

 nanoparticles were prepared by coprecipitation method employing natural iron sand as a raw material. The preparation was the same as explained in the former papers [48, 52]. First, iron sand was extracted by permanent magnet several times to obtain microsized Fe<sup>3</sup>

nanoparticles produced by the coprecipitation method were based on the following

Both reactions were maintained at room temperature. A complete reaction was indicated by the color change of the solution and the formation of black precipitation. Finally, the precipitated powders were rinsed several times using distilled water and then dried at 100°C for 1 h

paste solution, and then, they were stirred to obtain a uniform gel. Furthermore, the mixture gel was placed into a cylindrical mold to perform the similar F-T cyclic process as in the PVA hydrogels fabrication. The ferrogel samples were prepared by varying the concentration of

Basic characterizations using X-ray diffractometer (XRD) and transmission electron microscopy (TEM) were conducted to analyze the crystal structure and particle morphology of

nanoparticles in the PVA hydrogels were analyzed using small-angle X-ray scattering (SAXS)

 nanoparticles and ferrogels, respectively. Vibrating sample magnetometer (VSM) and superconducting quantum interference device (SQUID) measurements were taken to investigate the magnetic properties of the PVA ferrogels. Particle size and the distribution of Fe<sup>3</sup>

nanoparticles, as well as the number of F-T cycles.

OH were used as dissolving and precipitating agents, respectively.

Development of PVA/Fe3O4 as Smart Magnetic Hydrogels for Biomedical Applications

O4 + 8HCl → 2 FeCl<sup>3</sup> + FeCl<sup>2</sup> + 4H2 O (1)

**O4**

O4

O4 + 8NH4 Cl + 4H2 O (2)

http://dx.doi.org/10.5772/intechopen.71964

 **hydrogel (Ferrogel)** 

nanoparticles in the PVA hydrogel

O4

163

O4

zero velocity.

Fe3 O4

Fe3 O4

**4. Preparation of Fe3**

powders. HCl and NH<sup>4</sup>

chemical reaction [52, 53].

for ferrogel fabrication.

**based on iron sand**

O4

instrument as in the reported paper [48].

PVA and Fe3

Fe3 O4

Fe3

**O4**

2 FeCl<sup>3</sup> + FeCl<sup>2</sup> + 8NH4 OH → Fe3

**5. Fabrication and characterization of PVA/Fe3**

Ferrogel was fabricated by distributing the prepared Fe3

Sunaryono et al. have shown that the hydrogels owing the threshold PVA concentration of 23% in water content have the best mechanical properties [49]. Moreover, the lower Fe<sup>3</sup> O4 concentration has been found to be responsible for a weak magnetic response due to the increase of particle free volume and the decrease of interaction energy between magnetic nanoparticles and the cross-linked PVA hydrogel [48]. However, Sunaryono et al. [48, 49] stated a crucial problem is related to the durability of the PVA hydrogels and ferrogels prepared by F-T cyclic process.

In this chapter, at first, we provide a study of PVA hydrogel application in tissue engineering. Then, it is continued by investigation of the durability of ferrogels prepared by F-T cyclic process. Finally, the structural and magnetic properties of ferrogels are discussed briefly.
