**5. Water sorption and diffusion**

cells cultured on these materials demonstrated higher maturation compared with cells cul-

**Figure 3.** Fabrication process of rGO–PAA composites: (a) the GO nanosheets/PAA homogeneous solution was filtered by vacuum-assisted filtration into GO–PAA composites. Then after hydroiodic acid (HI) reduction, the rGO–PAA composites were obtained. (b) a digital photograph of rGO–PAA composites (c) and (d) cross-section surface morphology

Even though hydrogels do not need to endure temperatures higher than that of the human body, the improvement of thermal properties can increase its long-term operation. Thus, for example, the incorporation of polyurethane into polyacrylamide network in the form of an interpenetrating polymer network enhanced the thermal properties due to higher crosslinking density imparted by the hard segment content [22]. Though silica can improve the mechanical properties of hydrogels, the differential scanning calorimetry results of

[77]. However, composite hydrogels with functionalized graphene sheets (FGNS) showed an unprecedented shift in Tg of up to 40 and 30°C in poly(acrylonitrile) with 1 wt. % of

Another strategy to improve the thermal properties of hydrogels is by nanoparticle filling. Thus, crosslinking metal nanoparticles added into the polymer backbone of PHEMA

hybrids are complicated, showing two glass transition temperatures (Tg)

tured on pristine and randomly distributed CNTs in GelMA hydrogels.

with different magnifications of rGO–PAA composites. *Reprinted with permission from Ref.* [73].

**4. Thermal properties**

PHEMA/SiO<sup>2</sup>

98 Hydrogels

this nanomaterial [78].

Water sorption and diffusion of hydrogels are also very important in biomedical applications because these properties play a very important role in cell survival, especially in tissue engineering [5]. Thus, synthetic hydrogels such as PHEMA or PHEA are very important hydrophilic materials as these polymers were able to absorb and swell retaining large amounts of water within their structure [83–86]. The excellent water sorption property has made these kind of biomaterials very promising in a wide range of biomedical applications such as controlled drug delivery, tissue engineering, wound healing, etc. [6, 87]. The ability of hydrogels to absorb water arises from hydrophilic functional groups attached to the polymeric backbone, while their resistance to dissolution arises from cross-links between network chains [88]. However, these single-network hydrogels have weak mechanical properties in the swollen state and slow response at swelling. Therefore, although reinforcement of hydrogels is absolutely necessary, as already mentioned, the improvement of mechanical properties can significantly affect water sorption. For example, water sorption can be dramatically reduced by the reinforcement produced by the combination of hydrophilic and hydrophobic functional groups of polymers as multicomponent polymeric systems (**Figure 1**).

Reinforcement of hydrogels by GO loading can enhance significantly water sorption and diffusion. Thus, the swelling rates of graphene oxide / poly(acrylic acid-co-acrylamide) nanocomposite hydrogels increased with increase in the GO loadings to 0.30 wt. % and then decreased with further increasing GO loadings. It is worth noting that the hydrogel with only 0.10 wt. % GO exhibited significant improvement of swelling capacity in neutral medium, and could also retain relatively higher swelling rates to a certain degree in acidic and basic solutions. Furthermore, it has been reported very recently that a very low filling of GO can produce a very significant increase of water diffusion (almost 6 times faster) in crosslinked alginate (**Figure 4**) [48]. Therefore, these GO-based super-absorbent hydrogels have very potential applications in many fields such as biomedical engineering and hygienic products [50].

The mechanism of water diffusion [89] can also be altered by the reinforcement of hydrogels through any of the methods shown in Section 2. Thus, very promising biomaterials

for drug-releasing such as poly(acrylic acid)-GO composite hydrogels exhibit non-Fickian anomalous diffusion and their deswelling ratio decreases with increasing GO content [51]. Superabsorbent polymers of sodium lignosulfonate-grafted poly(acrylic acid-co-acrylamide), prepared by a new ultrasound synthetic method, shows also a non-Fickian water diffusion transport with a maximum water absorbency of 1350 g·g−1 [90]. PHEA hydrogels exhibit also a non-Fickian diffusion behavior s [83, 86]. However, other polymer chemically very similar, PHEMA, which is a very important water-swellable biomedical polymer, is controlled by Fickian diffusion [91]. Thus, copolymerized hydrogels based on 2-hydroxyethyl methacrylate (HEMA) and epoxy methacrylate (EMA) synthesized by bulk polymerizations showed that the swelling process of these polymers is also Fickian and the equilibrium water content

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It is remarkable that pH has a big influence in the swelling properties and diffusion mechanism of hydrogels. Thus, the swelling properties of semi-interpenetrating polymer networks of acrylamide-based polyurethanes decreased in acidic pH while a reverse trend was observed in basic pH. Nevertheless, these semi-IPNs were found to be hydrolytically stable in phosphate buffer solution, which render them potential materials for biomedical applications [22]. PAA is a pH-sensitive and biocompatible polymer that is being used in many biomedical fields [30] and has attracted considerable interest because of its therapeutic use, due to its ability to swell reversibly with changes in pH. Thus, GO functionalized with PAA (GO-PAA) by *in situ* atom transfer radical polymerization (ATRP) showed potential use as an intracellular protein carrier using bovine serum albumin (BSA) as a model protein [93]. This application is very important because proteins participate in all vital body processes and these perform an essential function inside cells as enzymes, transduction signals, and gene regulation. Another pH-sensitive terpolymer hydrogel, poly(acryl amide-co-2-acrylamido-2-methyl-1-propanesulfonic acid-co-acrylamido glycolic acid), with applications in drug release showed a quasi-Fickian diffusion mechanism with partly chain relaxation controlled diffusion. These hydrogels demonstrated a sharp change in its water absorbency and molecular weight between crosslinks of the network with a change

The effect of temperature on swelling properties of hydrogels is also very important [92]. Thus, hydrogels can be modified to exhibit fast temperature sensitivity, and improved oscillating swelling-deswelling properties as for example the thermosensitive poly(N-isopropyl

Microbial infections can lead to implant failure, which may cause major economic losses and suffering among patients despite the use of preoperative antibiotic prophylaxis and the aseptic processing of materials. Therefore, novel antimicrobial materials are urgently in need for medical uses [96]. For that reason, much effort is being done in the development of advanced hydrogels with inherent antimicrobial properties. Thus, syringe-injectable bioadhesive hydrogels prepared from mixing polydextran aldehyde and branched polyethylenimine, able

(EWC) decreased with increasing EMA content due to its hydrophobicity [92].

in the swelling media pH [94].

acrylamide-co-acrylic acid) hydrogels [95].

**6. Antimicrobial and antifouling activity**

**Figure 4.** Cryo-scanning electron micrograph of crosslinked alginate synthesized with a minuscule amount of GO and 18 wt.% of calcium chloride (with respect to the mass of sodium alginate) in the swollen state after 2 minutes of immersion in water at 24 ± 0.5°C (a). Apparent diffusion coefficients of liquid water (mean ± standard deviation) in calcium alginate hydrogels with different crosslinker contents with (black columns) and without (gray columns) 0.1 wt.% of GO (b). *Reprinted with permission from Ref* [48].

for drug-releasing such as poly(acrylic acid)-GO composite hydrogels exhibit non-Fickian anomalous diffusion and their deswelling ratio decreases with increasing GO content [51]. Superabsorbent polymers of sodium lignosulfonate-grafted poly(acrylic acid-co-acrylamide), prepared by a new ultrasound synthetic method, shows also a non-Fickian water diffusion transport with a maximum water absorbency of 1350 g·g−1 [90]. PHEA hydrogels exhibit also a non-Fickian diffusion behavior s [83, 86]. However, other polymer chemically very similar, PHEMA, which is a very important water-swellable biomedical polymer, is controlled by Fickian diffusion [91]. Thus, copolymerized hydrogels based on 2-hydroxyethyl methacrylate (HEMA) and epoxy methacrylate (EMA) synthesized by bulk polymerizations showed that the swelling process of these polymers is also Fickian and the equilibrium water content (EWC) decreased with increasing EMA content due to its hydrophobicity [92].

It is remarkable that pH has a big influence in the swelling properties and diffusion mechanism of hydrogels. Thus, the swelling properties of semi-interpenetrating polymer networks of acrylamide-based polyurethanes decreased in acidic pH while a reverse trend was observed in basic pH. Nevertheless, these semi-IPNs were found to be hydrolytically stable in phosphate buffer solution, which render them potential materials for biomedical applications [22]. PAA is a pH-sensitive and biocompatible polymer that is being used in many biomedical fields [30] and has attracted considerable interest because of its therapeutic use, due to its ability to swell reversibly with changes in pH. Thus, GO functionalized with PAA (GO-PAA) by *in situ* atom transfer radical polymerization (ATRP) showed potential use as an intracellular protein carrier using bovine serum albumin (BSA) as a model protein [93]. This application is very important because proteins participate in all vital body processes and these perform an essential function inside cells as enzymes, transduction signals, and gene regulation. Another pH-sensitive terpolymer hydrogel, poly(acryl amide-co-2-acrylamido-2-methyl-1-propanesulfonic acid-co-acrylamido glycolic acid), with applications in drug release showed a quasi-Fickian diffusion mechanism with partly chain relaxation controlled diffusion. These hydrogels demonstrated a sharp change in its water absorbency and molecular weight between crosslinks of the network with a change in the swelling media pH [94].

The effect of temperature on swelling properties of hydrogels is also very important [92]. Thus, hydrogels can be modified to exhibit fast temperature sensitivity, and improved oscillating swelling-deswelling properties as for example the thermosensitive poly(N-isopropyl acrylamide-co-acrylic acid) hydrogels [95].
