Novel Superabsorbent Cellulose-Based Hydrogels: Present Status, Synthesis, Characterization, and Application Prospects
Over the past century, hydrogels have emerged as an effective material for an immense variety of applications. This contribution provides a brief overview of recent progress in cellulose-based superabsorbent hydrogels, fabrication approaches, materials, and promising applications. Firstly, hydrogels fabricated directly from various polymerization processes are presented. Secondly, we review on the stimuli-responsive hydrogels such as the role of temperature, electric potential, pH, and ionic strength to control the role of hydrogel in different applications. Also, the synthesis route and its formation mechanism for the production of smart superabsorbent, macro- and nano-hydrogels are addressed. In addition, several applications and future research in cellulose-based superabsorbent hydrogels are also discussed in this chapter.
KeywordsHydrogel Polymerization reaction Superabsorbent Stimuli-responsive Biopolymer
Hydrogels are known as the water-absorbing polymeric materials that are able to form a flexible three-dimensional structure with about 90% of water in the gel base and 10% of polymer chains. The presence of cross-linking interaction between water and hydrophilic characteristic of polymer chains facilitates the water-insoluble product with significant mechanical strength and physical integrity [1, 2]. Since hydrogels can absorb up to 1000 times of dry weight in water, thus this water-absorbing polymers are favorable for a variety of applications, especially for human usage. There is rising demand for hydrogels to be used for personal care and hygiene (baby diapers, sanitary pads, adult incontinence pads, and soft contact lenses), pharmaceuticals (drug carrier system), food (gelatin dessert), agriculture (plant water crystals), and health-care products (scaffolds in tissue engineering, wound care dressings) . In addition to the existing market demand toward the hydrogel, continuous R&D activities have created a new opportunity in the development of intelligent materials for the biomedical areas, such as therapeutics, sensors, microfluidic systems, nanoreactors, and interactive surfaces .
Among the various types of biomaterials (e.g., polymers, composites, ceramics, and metals), hydrogels have shown high biocompatibility, tunable biodegradability, improved water retention ability, controlled release (especially for medicine or nutrients), preservation of stored components, easy to modify due to the presence of polar hydrophilic surface, and so on . However, the feasibility of applying hydrogels is still limited due to poor mechanical strength and the fragile nature of hydrogel. In addition, majority of the hydrogels are produced from synthetic polymers (e.g., polyethylene glycol, polyamides, poly(acrylic acid), poly(methacrylamide), poly(N-isopropylacrylamide), poly(hydroxyethyl methacrylate)), which is limited particularly in the food industry, due to the likelihood of impurities in the final product that may cause toxicity and potential environmental hazards [6, 7]. Therefore, novel or natural hydrogels with improved characteristics are still needed and will continue to remain an important direction for research.
Natural hydrogels are mainly derived from natural resources, such as alginate, chitosan, carrageenan, collagen, protein/peptides, matrigel, fibrin, gelatin, hyaluronic acid, and cellulose fibers. These materials render long service life, high capacity of water absorption, biodegradable, high biocompatibility, and high gel strength, which are the green alternative for synthetic polymers . Cellulose fibers are nontoxic and low-cost organic polymers in the form of polysaccharide, which consists of hundreds to thousands of glucose units (C6H10O5)n. It is an abundant lignocellulosic biomass which is found mostly in forestry wood, agricultural residues, industrial wastes, and municipal solid waste . Cellulose consisted of active hydroxyl functional groups (–OH), which can easily develop desirable hydrogels with tailored properties and product structure by chemically modifying the functional groups or using various types of synthesis technologies. Thus, the utilization of green cellulose materials for hydrogels can overcome the limitation of synthetic hydrogels, with enhanced properties that satisfy the requirement particularly in food and biomedical industry .
In this chapter, different hydrogel preparation technologies for synthetic and natural hydrogels will be discussed. In addition, focus toward the cellulose-based superabsorbent hydrogel was highlighted with a closer discussion on different kinds of stimuli-responsive cellulose-based hydrogels. The relationship between cellulose structure with hydrogel characteristics (mechanical strength, viscoelasticity, stress-strain, and swelling ability) was covered in this study. Last but not least, application of cellulose-based hydrogels and cross-linking mechanism was also discussed herein.
2 Synthesis and Properties of Hydrogel by Various Polymerization Reaction System
Examples of polymers, initiator, and cross-linkers for hydrogel production
Poly(hydroxyethyl methacrylate) (PHEMA)
Poly(vinyl alcohol) (PVA)
Poly(ethylene glycol) (PEG)
Poly(acrylic acid) (PAA)
Poly(methacrylic acid) (PMAA)
Alginate, fibrin, agarose, chitosan, gelatin, silk, carrageenan, hyaluronic acid, collagen, cellulose, protein/peptides, dextran, matrigel, starch
Ammonium persulfate-tetramethylethylenediamine (APS-TMEDA)
Ammonium persulfate-sodium sulfite-Mohr’s salt
1-[4-(2-hydroxyethoxy)-phenyl]-2-hydroxy-2-methyl-1-propane-1-one (Irgacure D-2959)
N,N′-methylenebisacrylamide (MBAm or MBAA)
Pentaerythritol tetraacrylate (PETRA)
Ethylene glycol dimethylacrylate (EGDMA)
Ethylene glycol diacrylate (EGDA)
Poly(ethylene glycol) diacrylate (PEGDA)
Ethylene glycol dimethacrylate (EGDMA)
2.1 Chemical Synthesis Methods
Chemically cross-linked hydrogels are known as permanent or chemical gels, where the polymeric network is formed via the covalently cross-linked of monomers precursors/polymer chains. The chemical gels reached an equilibrium swelling state under optimized polymer-water interaction parameter and the cross-link density. Thus, chemical gels are considered as ‘strong gels’ with good mechanical strength and durability .
Methods for different chemical cross-link hydrogels
Aqueous solution polymerization
Reaction between ionic and neutral monomers with multifunctional cross-linking agent
Polymerization is initiated thermally by UV irradiation or redox initiator system
Aqueous solvent serves as heat sink for polymerization process (e.g., water, ethanol, water-ethanol mixtures, and benzyl alcohol)
Known as chain-growth polymerization or anionic or cationic polymerization
The process involves initiation, propagation, and termination steps
Generation of free-radical activities induces the addition of monomers in polymer chains
Chemical reaction of functional groups
The cross-linking involves functional group (–OH, –COOH, –NH2) of hydrophilic polymers with polyfunctional cross-linking agents
Hydrophilic polymers having –OH groups form cross-link through cross-linking agents – aldehydes (e.g., glutaraldehyde)
Polyvinyl alcohol (PVA) cross-linked with glutaraldehyde hydrogels
(ii) Addition reaction
Bis or higher-functional cross-linkers may be used to react with functional groups of hydrophilic polymers through addition reactions
Cross-linking glycidyl methacrylate derivatized dextran (Dex-GMA) and dithiothreitol (DTT)
(iii) Condensation reaction
Reaction occurs between the functional group of –OH and –NH2 with carboxylic acids or derivatives to form polyesters and polyamides
Zinc phthalocyanine-PEG-alginate copolymer
Enzymes act as a catalyst in cross-linking by cleave or form a chemical bond with polymer chains without interference with other chemical functional groups in polymer molecules
For example, horseradish peroxidase, transglutaminase, tyrosinase, phosphopantetheinyl transferase, and lysyl oxidase
Enzymatic cross-linking of a nanofibrous multidomain peptide hydrogel
Inverse-phase suspension polymerization
Monomers and initiator are dispersed in the nonpolar solvent (e.g., n-hexane, toluene) as a homogeneous mixture (water in oil system)
Continuous stirring and utilization of low hydrophilic-lipophilic-balance (HLB) suspending agent/surfactant to maintain the dispersion of mixture
The final hydrogel products present in the form of powder or microspheres (beads) with desirable sizes
Polymerization of highly hydrophilic monomers, such as salts of acrylic and methacrylic acids, as well as acrylamide
For example, poly(methacrylic acid-co-partially neutralized acrylic acid) hydrogels prepared using SPAN 80 as the dispersant, heptane as the organic phase
High-energy electromagnetic irradiations (e.g., gamma, x-ray, and electron beams) are applied as an initiator/cross-linker to induce the formation of radicals from hydrophilic polymer chains for the cross-linking process
The process is initiator-free and render high purity of hydrogels
Gamma-radiation water-soluble polymer blends based on poly(vinyl alcohol) (PVA) and poly(ethylene glycol) (PEG)
Comparison between three polymerization approaches
Microwave irradiation polymerization
High efficiency, fast heat, and clean (mass shape products)
Inverse-phase suspension polymerization
Higher costs, complex, and unstable (particle products)
Aqueous solution polymerization
Lower cost, easy control, and stable (mass shape products)
2.2 Physical Synthesis Methods
Physically cross-linked hydrogels are known as reversible or physical gels. It is present in three-dimensional network via polymeric molecular entanglements and/or secondary interaction including ionic, hydrogen force or hydrophobic interactions. Physical gels are divided into two groups, which are strong physical gels and weak gels. The strong gels provide permanent physical interaction between polymer chains under certain experimental conditions. It shows similar characteristics as chemically cross-linked gels. Examples of strong physical bonds are lamellar microcrystals, glassy nodules, or double and triple helices. In contrast, physical gels with temporary connections between polymeric chains can lead to a reversible process. This cross-linkage leads to finite lifetimes of products and continuously restructuring ability. Examples of weak physical bonds are hydrogen bond, block copolymer micelles, and ionic associations [2, 6].
Methods for different physically cross-linking hydrogels
The gelation process involves the formation of microcrystals in the polymer structure due to the cycle of freeze-thawing
By homopolymer systems: Polyvinyl alcohol and calcium alginate gel rendered touch and elastic behavior after repeated freeze-thaw process
By stereocomplex: The presence of stereoisomers with opposite chirality (e.g., l-lactic acid and d-lactic acid) with high molecular weight
Polymers with ionic groups formed cross-linking with the presence of di- or trivalent counterions (metallic ions)
Cross-linking occur under mild condition: physiological pH and room temperature
Polyelectrolyte solution (e.g., Na+ alginate−) with a multivalent ion of opposite charges (e.g., Ca2+ and 2Cl−)
Block and amphiphilic graft copolymers
Self-assemble characteristic for amphiphilic (both hydrophilic and hydrophobic) graft and block polymers
The copolymers may consist of hydrophobic chains with hydrophilic grafts (or water-soluble polymer backbone)
Poly(lactide-co-glycolide) (PLGA) and polyethylene glycol (PEG) copolymers favor for drug delivery system
PEG and polybutylene terephthalate (PBT) copolymers
Hydrophobized polysaccharides (e.g., dextran, chitosan, carboxymethyl-curdlan, and pullulan)
Formation of hydrogen bonding occurs between polymers carrying carboxyl groups (–COOH)
Protonation favorable in low-pH condition
Hydrogen-bounded carboxymethyl cellulose (CMC)
Carboxymethylated chitosan (CMC) hydrogels
Poly(acrylic acid)- and poly(ethylene oxide)-based hydrogel
Poly(acrylic acid) (PAA) and poly(methacrylic acid) (PMAA) with polyethylene glycol (PEG)-based hydrogel
The presence of the mixture of polyanion-polycation will form complex coacervate gels
Polymers with opposite charges will tend to attract each other to form soluble and insoluble complexes under different concentrations and pH of respective polymer solutions
Polyanionic xanthan with polycationic chitosan
Proteins below its isoelectric point are positively charged and likely to associate with anionic hydrocolloids and form polyion complex hydrogel
Protein interaction involves block copolymers of Prolastin (consisted repetition of silk-like and elastin-like blocks)
Prolastin is fluid solutions in water and form the gel under physiological conditions as the crystallization of the silk-like domains occurs
Genetically engineered proteins interaction
2.3 Newly Emerging Approaches
Methods for different novel technologies
Solid-liquid interface technology
Polymerization occurs by immersed agarose gel rod loaded with acetic acid in the cellulose solution, to form onion-like and multilayered tubular cellulose-based hydrogels
Controllable size, layer thickness, and interlayer space of the multilayered hydrogels
Hydrogels render good architectural stability, solvent resistance, high compressive strength, and excellent biocompatibility
Multilayered tubular cellulose hydrogels
Well-aligned, highly ordered, and covalently cross-linked polyacrylamide (PAM) hydrogel microfiber produced by using electrospinning techniques
This technique is able to generate ordered structures from nanoscale to microscale fibers for biological muscle application
Highly aligned and covalently cross-linked polyacrylamide hydrogel microfibers
Cross-linking approach assisted by microwave led to strong irradiation penetrating ability, faster heating, and a cleaner process
Poly(vinyl alcohol) with either poly(acrylic acid) or poly(methyl vinyl ether-alt-maleic anhydride) forms cross-linking without the use of monomers, thus avoiding the purification step of unreacted species
Combination between poly(vinyl alcohol) with either poly(acrylic acid) or poly(methyl vinyl ether-alt-maleic anhydride)
3 Cellulose-Based Superabsorbent Hydrogels
Owing to the hydrophilic characteristic performance, superabsorbent hydrogels have a high capacity for water uptake, which can absorb, swell, and retain aqueous solutions up to hundreds of times from their own weight (dry sample). Since most of the superabsorbent hydrogels are produced from synthetic polymers (acrylics), the tendency for replacing these synthetics with greener alternatives is more than overwhelming due to the poor degradability and biocompatibility of synthetic superabsorbent . Thus, as an alternative to a greener route, cellulose-based superabsorbent hydrogel was invented. Cellulose (abundant biomass, biocompatibility, biodegradable, nontoxic, low cost and renewable, abundant hydroxyl groups) can be used to produce superabsorbent hydrogels easily with fascinating structures and properties which will be discussed in detail in this section.
3.1 Cellulose Structure and Biodegradability
The biodegradability characteristic for cellulose has been broadly investigated because of its capacity of molecular weight reduction, lower mechanical strength, and high solubility aspect. The great biocompatibility of cellulose, cellulosic, and cellulose disintegration has provoked the extensive utilization of cellulose-derived materials in biomedical utilizations. Moreover, the chemical alteration and cross-linking of water-solvable cellulosic material with bioresorbable component are able to produce degradable, absorbable, and resorbable cellulose-derived materials. In addition, cellulose and its subordinates are ecologically well disposed, as they are degradable by a few microscopic and macroscopic organisms that are present in our surrounding , which can disintegrate cellulose into cellulose-specific enzyme (i.e., cellulase) .
3.2 Water-Soluble Cellulose Derivatives
Chemical structure of soluble cellulose derivatives
3.3 Cellulose-Based Hydrogels and Cross-Linking Strategies
Hydrogels can be divided into those formed from natural polymers and those formed from synthetic polymers. On the basis of the cross-linking method, the hydrogels can be divided into chemical gels (covalent bond), physical gels (molecular self-assembly through ionic or hydrogen bonds), and irradiative cross-linking (formation of covalent bonding between polymer chains).
3.3.1 Physical Cross-Linking of Cellulose Derivatives
In the family of thermos-reversible gelling polymers for hydrogels, hydrophobically modified cellulose is one of the largest members. When hydroxyl groups are substituted partly by methyl groups or hydroxypropyl groups, some hydrogen bonds are prevented, and the resultant derivatives become water soluble . Methylcellulose (MC) aqueous solutions possess the unusual properties in forming reversible physical gels, due to hydrophobic interactions when heated above a particular temperature . On the other hand, hydroxypropyl methylcellulose (HPMC) has a higher gelation temperature than MC, which forms firmer gels with equivalent substitution and molecular weight. Evidence have indicated that the gelation of HPMC cellulose derivatives resulted from the removing of water molecules from methoxylated regions of the polymer . Sammon’s group  successfully modified hydroxypropyl methylcellulose with 9.1% hydroxypropyl and 29.3% methoxyl at 4 °C for 24 h. In addition, Sekiguchi et al.  discussed the hydrophobic interactions and hydrogen bonds contributed to thermally reversible gelation of methylcellulose aqueous solution. They were successfully modified cellulose acetate with dimethyl sulfoxide (DMSO) under a reaction condition of 60 °C and 1-h process. Subsequently, the sample underwent the methylation process (methylene chloride) and was further washed with deionized water.
As reported by Joshi et al. (2008), methylcellulose (MC) in cold deionized water shows a higher gelation rate at higher concentrations by using heating-cooling cycles. Initially, dried methylcellulose mixed with deionized water and heated till the temperature at 95 °C. The sample was allowed to cool down to 22 °C for at least 24 h, and finally the sample was maintained at a temperature of 4 °C. As a result, the gelation rate during the second heating-cooling cycle is higher than that in the first cycle .
Hydroxypropyl methylcellulose (HPMC) is a methylcellulose modified with a small amount of propylene glycol ether group attached to the anhydroglucose of the cellulose. Weiss’ group  has developed a series of biomaterials based on HPMC. The first generation of injectable calcium phosphate ceramic suspensions is composed of a mixture of HPMC solution and biphasic calcium phosphate granules. The aggregation and gelation behavior of HPMC (19–24% methoxyl and 7–12% hydroxypropyl) aqueous solutions is concluded as follows: (i) polymer reputation increases due to thermal motion, which led to a weaker network; and (ii) above 55 °C, the polymer chains become more hydrophobic, and polymer clusters start to form .
The second generation of hydrogel products that can suppress the long-term flow by easily controlling the cross-linking of silated HPMC (Si-HPMC) has been developed by Vinatier’s group  in 2009. Basically, Si-HPMC powder was solubilized in NaOH for 2 days. The solution was then sterilized by steam (121 °C, 30 min). To allow the formation of a reticulated hydrogel, the solution was finally mixed with N-(2-hydroxyethyl)piperazine-N′-(2-ethanesulfonic acid) (HEPES) buffer. The resulted Si-HPMC is nontoxic and biocompatible so that it can be widely used in biomedical areas, such as scaffolding for cell culture and cartilage model, and implanted in bone defects . In addition, Si-HMPC-based hydrogels are developed as a scaffold for the 3D culture of osteogenic cells, which would be suitable for both in vitro culture and in vivo injection. The results from the mineralization assay and gene expression analysis of osteoblastic markers and cytokines indicate that all of the cells cultured in 3D into this hydrogel exhibit a more mature differentiation status from cells cultured as a monolayer on plastic. This Si-HPMC hydrogel is well suited to support osteoblastic survival, proliferation, and differentiation as it is used as a new scaffold and represents a potential basis for an innovative bone repair material .
3.3.2 Chemical Cross-Linking of Cellulose Derivatives
The stable structure and effective swelling of cellulose-based hydrogels often require a chemically cross-linked network. Some difunctional molecules are employed as the cross-linker for cellulose or its derivatives to covalently bind different polymer molecules in a three-dimensional hydrophilic network .
Sannino et al.  exploited the superabsorbent hydrogels based on cellulose through cross-linking carboxymethyl cellulose (CMC) and hydroxyethyl cellulose (HEC) with a cross-linking agent such as divinyl sulfone (DVS). Then sodium hydroxide (NaOH) and poly(ethylene glycol) (PEG) which acted as spacers between cross-links were added into the solution. These polyelectrolyte hydrogels display a high sensitivity in sorption capacity with variations of the ionic strength and pH of the external solution. Besides, the superabsorbent hydrogels are also developed to treat edemas for body water elimination. If hydroxypropyl cellulose (HPC) hydrogels are synthesized at certain temperatures in the single-phase regime, they remain nonporous, whereas when cross-linked in the biphasic regime, it will turn to microporous structure. Additionally, Hirsch and Spontak  reported the dynamic mechanical properties and swelling capacities of these hydrogels as a function of cross-linking temperature. The results showed that the HPC hydrogels when cross-linked with ammonia (NH3) and epichlorohydrin (ECH) had excellent ability to absorb anionic dye with maximum adsorption capacity of 2478 (g/kg) which can be achieved at pH 3.96.
In 2008, Demitri et al.  reported the preparation of HEC and CMCNa hydrogels with citric acid as a cross-linker, which can overcome toxicity and material costs, as compared to divinylsulphone or with a carbodiimide cross-linking agent. Briefly, CMCNa and HEC (3:1) were mixed with citric acid which acts as a cross-linking agent. Results indicated that the swelling ratio of hydrogels depends on the reaction time and citric acid concentration, when the swelling degree reaches 900 with 3.75% of acid.
3.3.3 Irradiative Cross-Linking of Cellulose Derivatives
Irradiation is a useful method for the formation of covalent bonding between polymer chains. This method is advantageous because of the high purity of the hydrogel product without the use of toxic cross-linkers, thus enlarging the applications in food and pharmaceutical industries. However, only a small fraction (17–30%) of gel aggregates (lumps) can be obtained by γ-ray irradiation at a dose of 20 kGy from 20 wt% of biopolymer solutions (such as cellulose/ionic liquid/water, CMC, and carboxymethyl chitosan (CMCT) aqueous solutions), with the assistance of generated hydroxyl radicals [58, 59].
The electron beam (EB) irradiation in the vacuum seems to be able to increase the gel yield (the gel fraction reached up to 55% at 20 kGy and increased with the irradiation dose). Petrov group  successfully obtained an opaque spongy material via UV irradiation from 3 wt% of aqueous cellulose polymers (HPMC, HEC, and MC) with (4-benzoylbenzyl) trimethylammonium chloride (BBTMAC) as a photo initiator. At high energy doses and low polymer concentration (10 wt%), the degradation of the polymer chains competes with cross-linking, thus resulting in the destruction of network structure and a decrease in tensile strength. The occurrence of degradation was due to EB irradiation (higher radical number created in the system) or irradiation in an oxygen-free atmosphere to avoid the generation of oxides and peroxides.
4 Stimuli-Responsive Cellulose-Based Hydrogels
The smart hydrogel can be categorized as physical or chemical stimuli-responsive hydrogels. Physical stimuli (temperature, electric or magnetic fields, and mechanical stress) will affect various energy sources and alter molecular interaction at a critical onset point. However, the chemical stimuli (pH, ionic factors, and chemical agents) will change the interaction between polymer chains and solvent at the molecular level. Thus, the responsive cellulose-based hydrogels found a new generation of smart materials to be used in numerous fields (biomedical devices, scaffolds for engineered tissues, biosensors, and actuators).
4.1 pH-Responsive Hydrogels
pH-responsive hydrogels are produced of polymeric backbones with the ionic pendant groups that can accept or donate protons in response to an external pH change [46, 61]. The acid- or basic-side functional groups in polyelectrolytes undergo dissociation in a similar way as the acidic or basic groups of monoacids or monobases. The ionization on polyelectrolytes, however, is more difficult due to electrostatic effects of other adjacent ionized groups. So, the apparent dissociation constant (Ka) may be different from that of the corresponding monoacid or monobase. When the macromolecules are constituted by a huge amount of ionizable groups, such polymer is called polyelectrolyte. Hydrogels constituted by polyelectrolytes are, often, sensible to pH changes, which makes the hydrogel to swell (if the side functional groups are in an ionized state) or to collapse (if the side functional groups are not ionized). The process of swelling/collapsing of pH-sensitive hydrogel is reversible and may have strong applications in the pharmaceutical field because hydrogels can protect a given encapsulated drug from hostile environments, e.g., the presence of enzymes and low pH in the stomach region. A drug that can suffer degradation at acidic conditions can be transported through the gastric tract and be released in the colon if it is encapsulated in an appropriated pH-sensitive hydrogel. Hydrogels can also control drug release by changing the gel structure in response to environmental stimuli. Hydration under alkaline pH favors enzyme access to the hydrogel and its later enzymatic decomposition with the ensuing delivery of the drug entrapped in the hydrogel .
4.2 Temperature-Responsive Hydrogels
Chemically cross-linked thermosensitive hydrogels undergo volume change rather than sol-gel transitions. Certain molecular interactions, such as hydrophobic associations and hydrogen bonds, play a vital role in the abrupt volume change of these hydrogels at the critical solution temperature. In a swollen state, water molecules form hydrogen bonds with polar groups of polymer backbone within the hydrogels and organize around hydrophobic groups as iceberg water. At critical solution temperature, hydrogen bonding between the polymer and water, when compared with polymer-polymer and water-water interactions, becomes unfavorable. This forces the quick dehydration of the system, and water is released out of the hydrogel with a large gain in entropy, resulting in the shrinkage of the polymeric structure. Temperature-sensitive hydrogels will have a small variation in temperature which induces a phase transition, and therefore shrinking or expansion of the material is observed. This is because chemically cross-linked thermosensitive hydrogels undergo a volume change rather than sol-gel transitions. Theoretically, certain molecular interactions (hydrophobic associations and hydrogen bonds) play a vital role in the abrupt volume change of these hydrogels at a critical solution temperature. As a result, an abrupt transition in the 3D matrix occurs: water-solvated macromolecule quickly dehydrates and changes to a more hydrophobic structure.
4.3 Ionic Strength-Responsive Hydrogels
The swelling, loading, and releasing-solute capabilities of hydrogels are, sometimes, dependent on the ionic strength (IS) of the external fluid. Due to the diffusion and convection, an osmotic pressure is produced via the difference in the ionic concentration of the exterior solution and interior hydrogel, thus, causing the swelling and shrinking of the cellulose smart hydrogel .
4.4 Solvent-Responsive Hydrogels
The response to solvent is also a very important issue on stimuli hydrogels. Several aspects are exploited in this way. The change from hydrophilic to hydrophobic solvent (or the reverse) is a common strategy to induce the shrinking or expansion of a three-dimensional network .
4.5 Other Responsive Hydrogels
Other than stimuli-responsive cellulose-based hydrogel, there are a few different strategies for visible stimuli, for example, ultraviolet-visible, magnetic field, mechanical stress, and others to generate changes in hydrogels. As specified, a few frameworks have been produced to join more stimuli-responsive structure in the polymer systems . As stimuli-responsive cellulose-based hydrogel is actively developing, there is a pattern in growing new smart hydrogel to be responsive not only to stereotype stimuli but also to machine and analytical device that have a more responsive characteristic.
5 Structure Property Relationships in Hydrogels
Generally, hydrogels consist mostly of 60–90% fluid and 10–30% polymer . Due to its characteristic properties such as swell ability in the water, high water content and elastic nature similar to natural tissue, biocompatibility, and lack of toxicity, hydrogels have been utilized in a wide range of biological, medical, pharmaceutical, and environmental applications . Moreover, to achieve a successful network of hydrogels, it must consider its chemical cross-linking, physical entanglement, ionic bond, and hydrogen bond . In a broad sense, it shows that the hydrogels are categorized into chemical gels when the cross-links of hydrogen bonds in the main chains are replaced by the stable covalent bonds  and into physical gels when the links are held together by secondary weak bonds such as ionic bonds, hydrogen bonds, van der Waals and electrostatic interactions, or molecular entanglements [65, 67].
A different type of preparation method for hydrogels is another parameter to classify the hydrogels, which includes (i) homopolymer hydrogels, (ii) copolymer hydrogels, (iii) interpenetrating polymeric hydrogels, and (iv) multi-polymer hydrogels . The homopolymer hydrogels referred to as polymer networks are composed only of one type of hydrophilic monomer, while the copolymer hydrogels are composed of two types of monomers, where at least one is hydrophilic monomers . Meanwhile, the interpenetrating polymeric hydrogels are hydrogels that are prepared by swelling a network without any chemical bonds between them, such as a swelling process of polymer 1 in monomer 2, to make an intermeshing network of polymer 1 and polymer 2 . Last but not least, the multi-polymer hydrogels indicate that hydrogels consist of a combination of more than three types of monomers . Different types of hydrogel lead to different characteristic features, which included structure parameters, mechanical properties, and swelling effect.
5.1 Structural Parameters
The correlation length or the network mesh size (ξ) indicates the distance between the consecutive junctions, cross-links, or tie points. All the network parameters can be measured through a range of experimental techniques or calculated by the application of the network deformation theory .
5.2 Mechanical Properties
At present, there are a few methods available for characterizing the mechanical properties of hydrogel constructs. The mechanical properties of hydrogels are very difficult to describe and understand its structure. Besides, its mechanical behavior can be studied by using theories to analyze its polymer structures and to determine the effective molecular weight between cross-links and to provide information about the number of elastically active chains and cyclization versus cross-linking tendency .
5.2.1 Dynamical Mechanical Analysis
Theoretically, the ratio between the stress and strain may depend both on time and stress. The ratio will only depend on time if the deformations are kept small in order to obtain a liner material behavior. To determine the region of linearity, the preliminary strain sweep tests at fixed oscillation frequency are performed. Specifically, the dynamic moduli are monitored while logarithmically varying the strain amplitude, γo.
5.2.2 Viscoelastic Properties
According to Borzacchiello et al. , the mechanical spectra analysis can clearly distinguish the concentrated (entangled) polymer solutions and gels based on the concentration and its frequency. For the concentrated solution at low frequency, the solution presents a viscous behavior (G″ > G′), while at high frequency, it shows an elastic behavior (G′ > G″). The transition between viscous and elastic behavior is indicated by the cross point of G′ and Gil curves, as a function of frequency, occur at a given value of the frequency (ƒ*). Besides that, the common behavior of the concentrated solution when at low frequency shows that the solution behaves as a viscous liquid which the polymer chains are able to achieve the equilibrium configuration through the Brownian motion within the time scale of the experiment. Meanwhile, when at high frequency, the chains cannot be detached during the short period of oscillation, and it behaves as a temporary cross-linked network to accommodate stress by network deformation and elastic behavior (G′ > G″). The crossover frequency (ƒ*) depends on the intrinsic rate of disentanglement of polymer chains.
5.2.3 Stress-Strain Behavior
The rubber elasticity theory predicts the nonlinear stress-strain behavior. The theory predictions describe the experimental results fairly well at low extension but are less accurate at higher elongations.
5.3 Swelling Properties
6 Synthesis and Characteristics of Cellulose-Based Smart Superabsorbent
Throughout the years, the “superabsorbent polymer” has been developed and widely used in various areas due to its extraordinary properties [70, 71]. Due to its superior characteristics such as excellent hydrophilic properties, high swelling ratio, and improved biocompatibility, this superabsorbent hydrogel shows a high potential to attribute in many industries such as sanitary, agriculture, biomedical, food packaging, pharmaceuticals, and others [72, 73]. Generally, most of the superabsorbent hydrogels are produced from synthetic polymers (acrylics acid), and for the past several years, researchers have focused its attention to replace synthetic polymers with “greener” alternatives due to poor degradability and biocompatibility of the synthetic superabsorbent . Cellulose is one of the carbohydrate polymers with the most inexhaustible resources on Earth. This type of biopolymer is biocompatible, biodegradable, and nontoxic and is a low-cost material. Besides, cellulose consists of an abundance of hydroxyl groups that will interact between the hydrogen bond, which contributes to the cellulose’s mechanical strength, molecular structures, and its properties . Additionally, the advantages of cellulose-based superabsorbent hydrogels give superior characteristics such as high absorbency, high strength, good salt resistance, excellent biodegradable ability and biocompatibility, and other special functions that promise a wide range of applications in many fields [10, 65].
According to Sannino et al.  and Fekete et al. , the superabsorbent hydrogels were synthesized by both chemical and physical methods. The chemical method involves the synthesis processing of cellulose-based superabsorbent hydrogels via covalent linkages, and this includes aqueous solution polymerization, inverse-phase suspension polymerization, and even microwave irradiation pathways . Most of the cellulose-based superabsorbent hydrogels are synthesis via aqueous solution polymerization due to lower production cost, better control for heat of polymerization, and more convenience as compared to other methods. Besides, this method is mainly attributed to free-radical-induced polymerization, which monomers are polymerized through the action of initiators in the aqueous medium condition that is safe and harmless . Other than that, the physical synthesis methods refer to the molecular assembly cross-linked by hydrogen bonds or ionic bonds between the polymers or by the interaction between the polymers. These physical cross-link techniques include freeze/thaw cycle technology and hydrogen bond cross-linking, which are also adapted in some cases . Among the methods that are used for the preparation of cellulose hydrogels, physical approach is the best choice of process due to its simple pathway with zero solvent for environmentally friendly purposes .
7 Synthesis and Applications of Macro- and Nano-hydrogels
7.1 Synthesis Routes of Macro- and Nano-hydrogels
Recently, the synthesis of hydrogels by using biocompatible/biodegradable polymers in macro- and nanometer range is getting much attention. Among the research conducted are for the application in catalysis, electronics, bio-sensing, drug delivery, and nano-medicine . The incorporation of nanoparticles or macro-particles with various structures and morphologies into the polymeric hydrogel matrix can be considered as a facile and effective way to obtain enhanced characteristics of hydrogels, which is similar to the particle strengthening effect in polymer bulk matrix . For instance, the macro- and nano-sized hydrogels produced a higher area/volume ratio that significantly modifies the mechanical, thermal, and catalytic properties. As reported by Feeney et al. , under IUPAC classification, the micro-hydrogel is defined as a particle of hydrogel of any shape with an equivalent diameter of 0.1 to 100 μm. For nano-hydrogel, it is defined as a particle of hydrogel of any shape with an equivalent diameter of 1 to 100 nm. Generally, micro- and nano-hydrogels can be produced by several methods such as self-assembling, suspension, emulsion, precipitation or dispersion polymerization, micro-molding, droplet generation, microfluidics, and others .
7.2 Potential Application Fields
According to the Global Industry Analysts, Inc. report, the global superabsorbent hydrogel consumption was around 2.3 million metric tons in 2015, and it is expected that the global demand will continue to rise and reach 3.48 million metric tons in 2020 . The rapid growth and demand for hydrogels were reflected on the developing markets and its different applications. On the other hand, Transparency Market Research reported that the global superabsorbent hydrogel market was valued at US$ 10084.9 million in 2016 and was predicted to reach US$ 17487.6 million by 2024. This large market suggests a strong tendency to develop novel superabsorbent hydrogel materials with higher water absorbency and excellent mechanical properties. This section discusses about the highly potential applications of cellulose-based superabsorbent hydrogels, which range from the conventional use of hydrogels in agriculture and personal health care to the more innovative biomedical applications. In fact, there are a number of hydrogel products that have either been commercially available or are in the progress of development. Cellulose-based superabsorbent hydrogels act as promising biomaterials for hydrogel products which show the greatest significance for various fields of application and thus are extensively studied in industrial and academic research.
7.2.1 Agriculture and Horticulture
Hydrogels have been widely proposed over the last 40 years for agricultural and horticulture usage. There is an increasing interest in using superabsorbent hydrogels in agriculture and horticulture due to several reasons, which includes ameliorating the water availability for plants, increasing the water holding properties of growing media (soilless or soils substrates), optimizing the water resources, and reducing the water consumption. Due to its unique properties, several possible agricultural applications of hydrogels have been defined.
During the swelling of hydrogel, it turns the glassy material to a rubber-like state, which is able to store water even under compression. However, the swollen hydrogel can slowly release its absorbed water via a diffusion-driven mechanism when there is a humidity gradient between the outside environment and the inner part of the material. Generally, the water molecules loaded in the polymer network can be released in a sustained and controlled manner through diffusion. In order to make the cultivation possible in the arid, desert, and drought-prone areas (especially in South America, Africa, and west of Asia), where there is always a lack of sufficient available water resources, the dry hydrogel (i.e., xerogel) which is in the form of granules or powder is envisaged to be mixed with the soil in proximity of the plant root area. In addition, the hydrogel is possibly charged with the plants, pharmaceuticals, or nutrients . When the cultivation is watered (by either rain or irrigation), the water is absorbed and retained by the water, which can avoid the rapid water loss after watering due to drainage and evaporation. When the soil is in dried condition, the hydrogel will release the stored water and loaded nutrients in a continuous manner via diffusion mechanism as needed, keeping the soil or the substrate in the humid state over long periods of time . On the other hand, this process allows a high saving of water as well as the redistribution of the water resources that is available for cultivation in other applications. A further advantage of using this novel material in the agricultural application is related to its swelling effect in the soil. Basically, the dry form of hydrogel granules which is almost similar in size with the substrate granules is able to increase in size after swelling, thus increasing the soil porosity and providing a better oxygenation to the plant roots.
Unfortunately, most of the acrylate-based superabsorbent products available in the market are non-biodegradable, and some concern about toxicity was raised for agriculture application . This is harmful to cultivation and human consumption; thus, it should be avoided. As a result, the concern of the public and researchers toward the biological system and environment issues has led to an increase in demand for cellulose hydrogel-based products. Several studies have been conducted toward the manufacturing of biodegradable nature hydrogel-based superabsorbent. So far, the development of environmentally friendly cellulose-based hydrogels fits perfectly in the current trend as an alternative to replace the conventional acrylate-based superabsorbent hydrogels. Such studies have been conducted and patented by Sannino and coworkers [80, 81], in which degradable cellulose-based superabsorbent hydrogels have been successfully invented. It is worth mentioning that the obtained hydrogels exist in the form of powder or a well-defined-shaped bulky material with the strong memory of its shape after swelling. Such hydrogels are capable of absorbing up to 1 l of water per gram without releasing it under compression and are able to charge with nutrients and to be released under a controlled kinetic . Researches on the development of novel and green superabsorbent hydrogels for agriculture and horticulture have been further extended to recent years. In 2014, Li et al.  studied the effects of superabsorbent polymers on a soil-wheat (Triticum aestivum L.) system as a soil additive to increase crop yield and reduce the loss of soil water. The authors investigated the changes of crop yield, soil microbial activity, and water content between the modified soil and original soil; the results showed that the addition of superabsorbent hydrogels into the soil is able to improve the soil conditions with better crop yield and reduced detectable adverse effects on the soil microbial community. Besides that, Demitri et al.  proposed that the use of large-scale hydrogel might have an innovatory impact on the optimization of water resource management, especially in the agriculture field. The preliminary results revealed that the produced polyelectrolyte cellulose-based hydrogel could significantly increase the water retention capability of the soil and allow for the continuous release of water for a prolonged time effectively; thus, no additional watering is needed for the plants and soil. In fact, the proposed hydrogel potentially acts as an efficient storage and water reservoir in agriculture. A similar finding has been supported by Salmawi et al. , in which the superabsorbent hydrogel produced from acrylic acid and carboxymethyl cellulose with clay montmorillonite by gamma irradiation showed a higher percentage of swelling in distilled water and could act as a water-managing material in dried and drought-prone areas.
Pesticides are the most cost-effective way to control the growth of pest and weed. It is known that the cellulose-based superabsorbent hydrogels are used as pesticide carriers for special interest in terms of both sustainable and economic development. Hydrogels can be impregnated with fertilizer components such as nitrogen compounds, potassium ions, and soluble phosphate. Encapsulating the pesticides or herbicides into the cellulose-based superabsorbent hydrogels could be used to reduce the release rate of these herbicides . This is because the chemical trapped in a polymer network is normally unable to wash out immediately by water but is gradually released into the root zone before being absorbed by plants. Compared to those of conventional polymers such as poly(acrylic acid), polyacrylamide, polymethacrylic, cross-linked poly(vinyl alcohol), pectin, chitosan, and carboxymethyl cellulose, which normally have severe limitation such as rapid biodegradability in soil, cellulose-based superabsorbent hydrogel is able to increase the water capacity of soil, at the same time minimizing the water loss through evaporation and seepage . In the mixture with other active substances, it can be used as the polymer matrix to transfer bioinsecticides or herbicides, which is mainly designed to control, for example, proliferation of insect larvae into the soil. In general, the superabsorbent and fertilizers are combined via two methods, which have been well described in the literature [87, 88]. In the first approach, fertilizers are blended with cellulose superabsorbent hydrogels. In the second methodology, fertilizers are added to the reaction mixture and polymerized in situ in order to be entrapped in the superabsorbent. Results verified that these two procedures always result to a higher release rate.
Furthermore, the role of hydrogels as horticultural substrates enhances the soil water capacity. During rainfall or irrigation, the hydrogels bind the water in the soil to prevent it from seeping into deeper layers . Up to date, researchers have proposed the combination of inorganic clays, such as bentonite, kaolin, montmorillonite, etc., into pure cellulose superabsorbent hydrogels with the intention of improving the hydrogel strengths and swelling property and reduced production costs. In recent years, a study conducted by Bortolin et al.  has proven that polyacrylamide/methyl cellulose/montmorillonite nanocomposite superabsorbent hydrogels have presented a synergistic effect by rendering high fertilizer loading and the slow release of fertilizers. The results revealed that the produced cellulose-based hydrogels effectively reduced the loss of nitrogen by volatilization of ammonia.
In summary, the main advantages of cellulose superabsorbent hydrogels are controlled by the release of water, increase of soil porosity, long time maintaining soil humidity, and better oxygenation of plant roots. On the other hand, this type of hydrogels is biodegradable and low cost, has high holding capacity, and is an eco-friendly resource. Its application helps to reduce irrigation water demand, minimizes the plants death rate, increases the growth rate of plant and improves fertilizer retention in soil [91, 92].
7.2.2 Personal Health Care
Superabsorbent polymers have been introduced for various hygienic applications such as disposable diaper and feminine napkin industry for about 30 years ago due to their excellent water retention and the ability to retain the secreted liquids under pressure. In 1978, the commercial production of superabsorbent polymers began in Japan for the production of feminine napkins. This is considered to be the first generation of commercial superabsorbent hydrogels that has been successfully marketed . Previously, the commercial superabsorbent hydrogels were made through alkaline hydrolysis of starch-graft-polyacrylonitrile in the 1970s. However, the high expenses and inherent structural weakness (lack of sufficient gel strength) had contributed to the major factors of its market defeat . Further development of superabsorbent materials is being employed in baby diapers in France and Germany in the 1980s. In 1983, the low-fluff diapers which contained about 5 g superabsorbent polymers were launched. This was followed by the introduction of superabsorbent diapers with a thinner layer in several Asian countries, Europe, and the United States. The thinner layer of diapers and nappies was mainly due to the replacement of bulkier cellulose fluff with superabsorbent polymers that can retain much liquid more effectively .
Water absorbency of different types of common absorbent materials 
Water absorbency (wt%)
Wood pulp fluff
Soft polyurethane sponge
Facial tissue paper
Whatman No. 3 filter paper
Making recyclable and disposable products such as napkins, diapers, hospital bedsheets, and sanitary towels is one of the important targets for the modern industry due to environmental awareness of society. Therefore, an innovative idea to this issue has recently been proposed, which involves the production of cellulose-based hydrogels with fully biodegradable properties. At present, the superabsorbent hydrogels contained in sanitary napkins are mostly derived from polymerized acrylamide or acrylic acid, which is a costly process, and the final product is environmentally unfriendly and poorly degradable . Due to these reasons, some novel types of hydrogels composed of a mixture of hydroxyethyl cellulose and sodium carboxymethyl cellulose cross-linked with divinyl sulfone have been innovated. This hydrogel material is able to swell like conventional superabsorbent polymer, which exhibits higher water retention under centrifugal loads and swelling kinetics due to the capillary effects and the resulted introduction of microporous structures into hydrogel .
In order to establish more innovative methods for developing novel and new hydrogel products, many attempts have been made, which possess better swelling capabilities and are able to retain more fluids absorbed under the existence of external pressure or applied restraining force. Liu et al. reported a novel tactics for the production of eco-friendly superabsorbent hydrogels incorporated with flax yarn waste for sanitary napkin applications . Their study proved that the product obtained exhibits from several outstanding properties such as excellent biodegradability, superabsorbent, and good in retention of artificial blood solution as compared to the currently commercialized, marketed sanitary napkin products. A similar study has been reported by Zhang et al., in which a flax cellulose-based superabsorbent composite was synthesized by the free-radical graft copolymerization of acrylic acid and acrylamide . The results revealed that the yielded composite material attained the best water absorbency of urea. Most importantly, they found that 46.6% of the remaining residue after buried in soil after 90 days presented an excellent biodegradability. In modern times, a lot of convenient and comfortable disposable health-care products made up of hydrogels have been reported in literature; however, biodegradable health-care products have either not been commercially available or been industrialized . In reality, more than 90% of superabsorbent composites are landfilled or incinerated after usage. This will cause serious environmental problems, undesirable water-keeping capacity, and higher cost that limit its practical applications . Hence, continuous effort needs to be done in order to convert the cellulose-based superabsorbent hydrogels into the core layer of health-care products.
Further developments in the personal health-care area are expected with the formulation of the superabsorbent hydrogel materials containing enzymes and other additives in order to prevent unpleasant smells or infections. Furthermore, considering the scale of production of these materials is prerequisite as there is a clear need for environmentally friendly hygiene products that undergo biodegradation. Thus, it has a high value in the development of novel, green superabsorbent hydrogels by minimizing the consumption of chemicals or improving the degradability of disposed hydrogels. In this context, recent innovations about the cellulose-based hydrogels have move toward the implementation of an environmentally sustainable production process  as well as utilization of the nontoxic cross-linking agents during the process .
7.2.3 Water Treatments
Rapid industry developments had caused a series of severe problems to the surroundings and the environment, such as water contamination. The release of wastewater that consists of heavy metal ions into the local waterway or environment can be harmful to plants, humans, and animals. Pollution resulted from heavy metals has been accorded more attention due to the increase in awareness regarding the hazardous effects of heavy metal ions in the environment. A number of technologies have been established for water treatments, which mainly include chemical oxidation, adsorption, pressurized membrane-based separation, etc. However, several disadvantages such as high energy consumption and the pollution caused by traditional materials have been reported. Therefore, research-scholars have shifted their attention to the cellulose-based superabsorbent hydrogels.
Zhou and coworkers  prepared a novel magnetic hydrogel bead in order to remove Pb2+ from the polluted streams. The authors blended the chitosan with carboxylated cellulose nanofibrils, amine-functionalized magnetite nanoparticles, and poly(vinyl alcohol) by using instantaneous gelation method. This novel magnetic hydrogel beads can be used to absorb Pb2+ metal ion in sewage effectively, which are mainly attributed to the various carboxylate groups on the carboxylated cellulose nanofibrils as well as the abundant amino and hydroxyl groups on the chitosan . Tripathy et al.  examined the metal ion sorption behavior of cellulose-based superabsorbent hydrogels (sodium carboxymethylcellulose-g-N-vinylformamide) to the selected metal ions including Hg2+, Pb2+, Zn2+, Ni2+, and Cu2+. They found that the values of the percent ion uptake were 8.7, 9.0, 9.8, 11.5, and 13.8 at the maximum values, respectively. On the other hand, a study reported by Kamel et al.  proved that the cyanoethyl cellulose-based superabsorbent hydrogels were capable of the adsorption of copper (II) ions from aqueous solution effectively. The authors reckoned that metal ion removal mainly depends on the protonation and deprotonation properties of its acidic and basic groups, specifically pH value. A similar finding has been reported by Abdel-Aal’s group  in which the metal ion absorption capacities increased with the increase of pH values. They prepared the maize starch-acrylic acid hydrogels by radiation grafting technique, and the obtained hydrogels were used to remove the heavy metal ions (Fe3+, Cr3+, Pb2+, and Cd2+) from wastewater. Hashem et al.  reported three types of hydrogels which were prepared via graft polymerization of acrylonitrile into maize starch and ceric ammonium nitrate which were used as the initiator. The study has proven that the prepared hydrogels could be used for the removal of Hg(II) ions from aqueous solutions with the maximum adsorption capacity of 1250 mg/g. The adsorption data agreed with the Freundlich and Langmuir isotherms.
Apart from the metal ion pollution, increasing oil contamination and oil spills from the industrial wastewater have become a new source of water pollution. In order to be cost-effective and an energy-efficient oil separation, Rohrbach’s group  has fabricated the nanofibrillated cellulose-based superabsorbent hydrogel as the filter for water/oil separation. The fabricated filter possesses oleophobic and hydrophilic properties, resulting in an increase in filter life and reduced negative impact toward the environment while showing the efficiency of more than 99% under gravitational force. Basically, cellulose nanofibril-based aerogels have been of great interest as absorbent materials owing to their biodegradability, high absorption capacity, large surface area, and low density. In addition, the hydrophobic aerogels have been designed to contribute excellent absorption tendency for various oil from water .
7.2.4 Biomedical (Controlled Drug Delivery, Scaffolds for Regenerative Medicine, Wound Dressings)
In 1960, poly-2-hydroxyethylmethacrylate was used as a synthetic biocompatible hydrogel for the application of contact lens. Wichterle and Lim reported the cross-linked poly-2-hydroxy-ethylmethacrylate hydrogel using ethylene glycol dimethacrylate as a starting material . The hard contact lenses are primarily made up of hydrophobic materials such as poly(hexa-fluoroisopropyl methacrylate) or poly(methyl methacrylate), while soft lenses are based on hydrogels . Usually, contact lenses are classified as soft or hard, according to their elasticity. Albeit the hard lenses are longer lasting compared with soft lenses, they tend to be poorly accepted by the users and require a lengthier adaptation period. Many efforts are made to obtain lenses with good oxygen permeability. For this purpose, several hydrophilic monomers are proposed including methacryloylamino-4-t-butyl-2-hydroxycyclohexane, 4-t-butyl,2-hydroxycyclohexyl methacrylate, and 4-t-butyl,2-hydroxycyclopentyl methacrylate with hydroxyethyl methacrylate and N-vinyl-2-pyrrolidone. After that, a significant progress has been accomplished, and a diverse range of polymers have been used for the fabrication and synthesis of hydrogels for various applications.
The cellulose superabsorbent hydrogels have gained noticeable interests in the application of controlled drug delivery system. This is due to their remarkable characteristics such as versatility and flexibility in fabrication; high tunability in the chemical, physical, and biological properties; variety in composition; excellent biocompatibility; and high moldability in shape . One of the most notable characteristics of hydrogels is the highly porous structure, which permits a depot maintaining a high local concentration of an active pharmaceutical ingredient or drug at the targeted tissues over a long period, ranging from hours to weeks . The transportation capability of high porosity of hydrophilic/hydrophobic molecules is important for a hydrogel-based drug delivery system. The drug diffusion and release behavior via the polymer network can easily be adjusted by manipulating the cross-linking density in the gel matrix and monitoring the porosity (i.e., mesh size) of hydrogels . Also, the porous structure allows the drugs to be loaded and then released continuously. So far, the drug can be loaded into a hydrogel followed by releasing to the targeted place through several mechanisms: swelling controlled, chemically controlled, diffusion controlled, and environmentally responsive release. He et al.  fabricated the multilayered tubular and onion-like cellulose-based superabsorbent hydrogels for the first time. Their results indicated that the multilayered superabsorbent hydrogels are important and have a great potential application in the biomedical field due to its non-cytotoxicity, good architectural stability, good biocompatibility, and solvent resistance against acetone, ethanol, dimethylacetamide (DMAc), and sodium hydroxide aqueous solution.
It is known that the drug release rate is highly dependent on the network parameters (i.e., mesh size and degree of cross-linking) as well as the water content of the swollen hydrogel . In the typical matrix systems, the drug is dissolved or dispersed uniformly throughout the 3D structure of the hydrogel. The drug is released through the macromolecular pores or mesh, and the initial release rate of drug is proportional to the square root of time. Depending on the structure of the hydrogels used, the chain dissolution takes place along with the swelling process due to the physical nature of the hydrogel network; thus, the release of drug results from the complex combination of diffusion, swelling, and erosion mechanisms. When using hydrogels to modulate the bioactive molecules and drug release, the loading of the drug is performed either during network formation or after cross-linking . Moreover, the bioactive molecule can be physically or covalently linked to the polymer network and further tune the release rate. It is important to note that the cross-linking reaction has to be conducted under mild conditions in order to prevent the denaturate of loaded bioactive molecule. Although hydrogel formulations for transdermal and oral delivery can be non-degradable, the direct delivery of drugs to different body interest sites requires the hydrogel biodegradation. This is to avoid foreign body reaction, and further surgical removal is necessary . At present, injectable hydrogel formulations are mostly appealing and still under investigation. Recently, a new and novel injectable cellulose nanocrystal-reinforced superabsorbent hydrogel has been developed by Yang’s group  which could maintain their original shape for more than 60 days when immersed in 10 mM phosphate buffered saline or purified water and exhibits the excellent storage modulus. These properties make nanocellulose-reinforced injectable hydrogels a high potential interest for various biomedical applications such as tissue engineering matrices or drug delivery vehicles.
In the last decade, the use of excellent biocompatibility cellulose hydrogel and its derivatives as biomaterials for the design of tissue engineering scaffolds has received increasing attention. Regenerative medicine is an interdisciplinary research which deals with the induced regeneration of organs and tissues in vivo, by means of a scaffolding template or material that support and guide the cells during the synthesis of new tissues. In other words, it involves the replacement or improvement of specific organs or tissues using engineered materials and synthetic strategies. Basically, the superabsorbent hydrogels can be altered by using linker molecules that enable covalent or non-covalent molecular interactions between the hydrogel matrix and its surroundings in order to enhance the mechanical performance and tissue-/cell-adhesive properties .
For an ideal tissue regeneration, the generated scaffold has to be biodegradable with a reasonable biodegradation rate that matches with the biological process of the body. Practically, a slow degradation process is often favored to minimize the risk of premature resorption of the scaffold. Due to the bio-durability of cellulose, it is a suitable candidate for the design of tissue engineering scaffolds. However, it is known that a too slow degradation or a bio-durable material may cause the undesired biological responses in the long term, such as foreign body reaction, which limits the applications of cellulose in regenerative medicine. In fact, several studies [113, 114] have been conducted to prove the potential application of cellulose-based hydrogels for inducing the regeneration neural tissues, cartilage, and bone. A final remark about the development of regenerative medicine concerns the important role played by the scaffold porosity, which enhances the infiltration, attachment, and survival of cells within the scaffold. Owing to its nano-dimensional mesh structure , the superabsorbent hydrogels are usually employed to the small tissue defects while failing in larger implants. Several novel techniques for producing porous hydrogels had been summarized in several review papers [3, 45] and might be of great value in improving the regenerative potential of cellulose-based superabsorbent hydrogels.
In addition, there has been considerable interest in using cross-linked carboxymethyl cellulose (CMC) as tablet disintegrants. In order to achieve this, the cellulose superabsorbent hydrogels in powder form is mixed well with other excipients and thus is compressed to a tablet. Sadly, the cellulose-based superabsorbent hydrogel tablets may get soften at high-humidity condition, and thus, it may have an instability concern to the moisture-sensitive drugs . Tissue engineering is the latest application of hydrogels which is mainly served for three purposes including as delivery vehicles for bioactive substances (for encapsulation of secretory cells and promotion of angiogenesis), as space-filling agents (to prevent adhesion, employed for bulking and as biological glue), and as three-dimensional structures that organize cells and present stimuli in order to ensure the development of a required tissue in the body (i.e., smooth muscle, bone, and cartilage) .
Superabsorbent hydrogels are widely applied in the wound treatment. During the wound healing, several processes including inflammation, autolytic debridement, granulation tissue formation, and reepithelialization are normally involved. Large wounds result in high risk of infection as well as loss of large amounts of fluids. Therefore, suitable wound dressings are designed to promote healing while protecting the wound from further infection. For an ideal wound management product, it should have numerous properties such as being able to absorb excess toxins and exudate, preserve the wound from external infection, prevent excess heat at the wound, maintain good moisture between the dressing and wound, have good permeability to gases, be easy to remove without further trauma to the original wound, and be supplied completely sterile . It is known that a moist environment encourages rapid healing; therefore, the hydrogels in the form of sheets or amorphous state are optimal candidates for the development of wound dressings . Basically, amorphous hydrogels are physically cross-linked, and their viscosity will be decreased when absorbing the physiological fluids. Amorphous-state hydrogels are generally reapplied daily, while the sheet structure hydrogels are usually changed 2–3 times weekly . The hydrogels may be packaged in foil packets or in tubes and can reinforce with a polymeric mesh or gauze for the ease of removal and to prevent gel liquefaction. The advanced dressings are aimed to keep the moist environment at the applied site, allowing the fluids to remain close to the wound rather than spread to the healthy, unaffected skin areas . The significance of the moist condition around the wound as a factor accelerating the healing process was first observed in 1962 by Winter  but only has received much attention recently.
Commercially available hydrogel for application of wound dressings 
Hydrogel wound dressing
Smith & Nephew
Propylene glycol, water, NaCMC
NaCMC, silver ions (1.2%)
Water, NaCMC, propylene glycol, pectin
Water, calcium alginate, CMC
Johnson & Johnson
Calcium alginate, silver ions (8%), CMC
8 Formation Mechanism of Cellulose-Based Hydrogels
In general, there are three main types of hydrogel-forming mechanisms: chemical cross-linking, ionotropic cross-linking, and complex coacervate formation. The mechanism for the formation of hydrogels (gelation behavior) has a direct and significant impact on the methods used to fabricate the hydrogel component for tissue engineering. Certain gel-forming processes resulted in the rapid prototyping fabrication process, while the slower fabrication techniques (i.e., porogen leaching) are suitable for robust hydrogels, which normally require more time to develop . All hydrogels possess physical attraction between macromers due to the presence of hydrogen bonding and entanglements among one another . Unfortunately, these physical interactions are strong enough only for the formation of a weak gel but not strong enough for tissue engineering applications or layer-upon-layer fabrication. Therefore, a hydrogel is usually intended for tissue engineering applications which must be strengthened through additional chemical cross-linking or electrostatic interactions.
In the current era, chemical cross-linking is the highly resourceful method for the formation of hydrogels having an excellent mechanical strength. Cross-linking is responsible for the three-dimensional network structures of hydrogels and their physical properties (i.e., swelling and elasticity) that are attributed to the presence of chemical or physical cross-links within polymer chains. The cross-linking level of the hydrogels is also vital because the physical states of the hydrogels can be altered by changing the cross-linking level . In this process, a cross-linking agent is added to a diluted hydrophilic polymer solution, and the polymer must have a suitable functionality to react with the cross-linking agent. This process is applicable for preparation of hydrogels from synthetic and natural hydrophilic polymers .
Ionotropic hydrogels are formed from the electrostatic interactions between polycations and anions or polyanions and cations. For instance, chitosan is a polycationic polymer comprised of glucosamine residues, which form a firm ionotropic hydrogel upon addition of phosphate ions and which are positively charged above its isoelectric point . Another example is alginate, a polyanionic polymer containing glucuronic and mannuronic residues, which will form a firm ionotropic hydrogel with calcium ions . Usually, these hydrogels are able to form a firm hydrogel upon cooling; therefore, it is particularly useful for use in rapid prototyping fabrication techniques or for in situ tissue engineering . Normally, ionic cross-links are beneficial for biomedical applications due to its self-repair properties. Thus, it is proposed to be used as cartilage tissue scaffolds which consist of epoxy amine polymers and gellan gum (a water-soluble anionic polysaccharide) .
Complex coacervate hydrogels (as referred to polyelectrolyte complexes or polyion complexes) are formed upon mixing of a polycation and a polyanion with one another (i.e., poly(l-lysine) and alginate) or with an amphoteric polymer (i.e., gelatin and chondroitin sulfate) [20, 128]. This approach is based on the principle that the opposite charges of the polymers stick together to form either soluble or insoluble complexes, depending on the pH and concentration of the solutions . Hydrogels can be produced by a variety of cross-linking methods as well as agents. However, most of the cross-linking agents are toxic and must be eliminated from the hydrogel before contact with the body or cells.
Considering the desirable features of hydrogels in terms of biocompatibility, biodegradability, high water content, controllable swelling behavior, low cost, hydrophilicity, and non-toxicity characteristics, cellulose-based superabsorbent hydrogels that are made from natural biomass resources are drawing attention to both industrialist and academicians. These types of novel hydrogels are potentially used for a variety of industrial applications such as drug delivery system, agriculture, tissue engineering, water engineering, hygiene products, wound dressing, and more. In this chapter, we had summarized several polymerization reaction systems that were widely used for the superabsorbent hydrogel production. In addition, stimulate-responsive cellulose-based hydrogels established a new generation of green materials to be applied in several fields, such as pharmaceutical and medical systems. According to different applications, these materials are able to respond to various internal and external stimuli and are sensitive to the changes of temperature, pH, ionic strength, and solvent system. Undoubtedly, superabsorbent hydrogels derived from cellulose and cellulose derivatives offer abundance of promising opportunities in various industries’ usage.
10 Outlook/Future Scope
This chapter discusses the current progress of cellulose-based superabsorbent hydrogels from different aspects. Generally, cellulose-based superabsorbent hydrogels possess several favorable properties such as biocompatibility, biodegradability, hydrophilicity, transparency, low cost, and non-toxicity. Therefore, these bio-based materials offer a wide variety and diverse range of applications for agriculture and horticulture, water treatments, personal health care, and biomedical industries. Nevertheless, some of the novel applications need to be explored, such as electronics, catalysis, capacitors, dye-sensitized solar cells, plugging agent, biosensor, and fire control. Up to date, the established conventional hydrogel-based product could not meet the requirements of the present day and thus the future development on superabsorbent hydrogels by emerging natural biomass resources (cellulose or cellulose derivatives) with the intention of achieving the demands for different product requirements. From the economic and application point of view, the performance of superabsorbent hydrogels (e.g., distinctive mechanical strength, anti-mildew properties, swelling capability, and electrochemical properties) can be further improved in order to expand to more industrial field. As a result, intense research on the production of cellulose-based superabsorbent hydrogels has to be conducted continuously. It is worth mentioning that cellulose fibers are low cost and is an environmentally friendly material, which is the suitable alternative of petroleum-based materials. Up to date, many hydrogel-based drug delivery devices and scaffolds have been designed, studied, and patented; however, not much of the products are able to reach commercialization stage. On the other hand, commercial hydrogel products for tissue engineering and drug delivery are still limited. It is believed that the limited commercial products with hydrogels in these areas are due to high production costs. Furthermore, advanced technologies need to be further developed in order to produce superabsorbent hydrogels with intrinsic and unique properties. Most important is an in-depth study on the reaction mechanism, and swelling kinetics of superabsorbent hydrogels originated from interdisciplinary angles is needed for deeper investigation.
The authors are grateful for the financial support from the University of Malaya: SATU Joint Research Scheme (ST015-2017) and Postgraduate Research Grant Scheme (PPP) (PG249-2016A, PG253-2016A).
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