Materials Science and Engineering C 79 (2017) 958–971

Contents lists available at ScienceDirect

Materials Science and Engineering C

journal homepage: www.elsevier.com/locate/msec

Review

A mini review on hydrogels classification and recent developments in

miscellaneous applications
Kokkarachedu Varaprasad a,⁎, Gownolla Malegowd Raghavendra b, Tippabattini Jayaramudu c,
Murali Mohan Yallapu d, Rotimi Sadiku e
a
Centro de Investigación de Polímeros Avanzados, CIPA, Av.Collao 1202, Edificio Laboratorio CIPA Concepción, Chile
b
Department of Packaging, Yonsei University, Yonseidae-gil, Wonju, Gangwon-do 220-710, Republic of Korea
c
Center for Nano Cellulose Future Composites, Dept. of Mechanical Engineering, Inha University, 253 Yonghyun-Dong, Nam-Ku, Incheon 402-751, Republic of Korea
d
Department of Pharmaceutical Sciences, Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN 38105, USA.
e
Department of Polymer Technology, Tshwane University of Technology, CSIR Campus, Building 14D, Private Bag X025, Lynwood, 0040 Pretoria, South Africa

a r t i c l e i n f o a b s t r a c t

Article history: Hydrogels are composed of three-dimensional smart and/or hungry networks, which do not dissolve in water but
Received 28 September 2016 swell considerably in an aqueous medium, demonstrating an extraordinary ability to absorb water into the retic-
Received in revised form 9 May 2017 ulated structure. Such inherent feature is a subject of considerable scientific research interest which leads to a
Accepted 14 May 2017
dominating path in extending their potential in hi-tech applications. Over the past decades, significant progress
Available online 15 May 2017
has been made in the field of hydrogels. Further, explorations are continuously being made in all directions at an
Keywords:
accelerated pace for their extensive usage. In view of this, the present review discusses the subject on the miscel-
Hydrogels laneous hydrogels with regard to their raw materials, methods of fabrication and applications. In addition, this
Classification article summarizes the classification of hydrogels, based on their cross-linking and physical states. Lately, a
Raw materials brief outlook on the future prospects of hydrogels is also presented.
Methods of fabrication © 2017 Elsevier B.V. All rights reserved.
Application

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 959
2. Hydrogels classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 959
2.1. Classification based on cross-linking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 959
2.1.1. Physically cross-linked hydrogels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 959
2.1.2. Chemically cross-linked hydrogels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 961
2.2. Classification based on physical state . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 961
2.2.1. Solid hydrogels. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 962
2.2.2. Semisolid hydrogels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 963
2.2.3. Liquid hydrogels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 963
3. Recent development in miscellaneous application fields. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 964
3.1. Superabsorbent hybrid hydrogels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 964
3.1.1. Raw materials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 964
3.1.2. Preparation methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 964
3.1.3. Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 964
3.2. Conducting polymer hydrogels. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 965
3.2.1. Raw materials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 965
3.2.2. Preparation methods for conducting polymeric hydrogels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 965
3.2.3. Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 965
3.3. Polysaccharide-based natural hydrogels. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 965
3.3.1. Raw materials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 965
3.3.2. Preparation methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 965

⁎ Corresponding author.
E-mail addresses: prasad@cipachile.cl, varmaindian@gmail.com (K. Varaprasad).

http://dx.doi.org/10.1016/j.msec.2017.05.096
0928-4931/© 2017 Elsevier B.V. All rights reserved.
 K. Varaprasad et al. / Materials Science and Engineering C 79 (2017) 958–971 959

3.3.3. Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 966

3.4. Protein-based hydrogels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 966
3.4.1. Raw materials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 966
3.4.2. Preparation methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 966
3.4.3. Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 966
3.5. Hydrogels based on synthetic polymers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 966
3.5.1. Raw materials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 967
3.5.2. Preparation methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 967
3.5.3. Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 967
4. Conclusion and future prospective . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 967
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 968
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 968

1. Introduction publications and technical reports dealing with polymeric hydrogels

‘Hydrogels’ are the cross-linked polymeric materials that have been
playing significant roles in various fields. Hydrogel came into light with
the establishment of the first synthetic hydrogels by Wichterle and Lim
[1] in 1954. Hydrogels are three-dimensional (3D), insoluble, cross-
linked and tissues like polymer networks that are able to retain a large
amount of water and biological fluids in their swollen state. The interac-
tion between polymeric chain networks and water or biological fluids
occur through capillary, osmotic and hydration forces, which are coun-
ter-balanced, causing expansion of chain networks [2]. Such equilibrium
state of hydrogel depends on the magnitude of these opposing effects
which determines some inherent properties of the hydrogel, including
internal transport, diffusion characteristics, and mechanical strength
[3].
Over the years, researchers have defined hydrogels in many differ-
ent ways. The most commonly used definition is that the hydrogel is a
water-swollen and cross-linked polymeric network, produced by the
simple reaction of one or more monomer/polymer/cross-linker units.
One more description is that it is a polymeric material that exhibits
the ability to swell and retain a large amount of water in its three-di-
mensional network, however, will not dissolve in water [4]. In another
way, they are defined as polymeric systems that show the capability
of swelling in water and retaining a significant fraction (N20%) of
water inside their 3D structure, without dissolving in water [5]. The
terms gels and hydrogels are used interchangeably by food and bioma-
terial scientists to describe polymeric cross-linked network structures.
Gels are defined as a substantially dilute cross-linked system and
these are categorized, mainly as weak or strong depending on their
flow behavior in steady-state [6]. In a broader term, hydrogels are a hy-
drophilic polymeric network of three-dimensionally cross-linked struc-
tures achieved from a class of natural/synthetic polymeric materials that
absorbs a substantial amount of water. Cross-linking facilitates their in-
solubility in water because of the ionic interaction and hydrogen bond-
ing [7]. It also provides the essential mechanical strength as well as
physical integrity to the polymeric hydrogels [8].
Hydrogels are being applied to food additives, pharmaceuticals, bio-
medical implants, tissue engineering and regenerative medicines, diag-
nostics, cellular immobility, cell encapsulation, separation of
biomolecules or cells and barrier materials for the regulation of biolog-
ical adhesions, biosensor and biomedical microelectro-mechanical de-
vices [9–11]. Furthermore, they have been used in diverse
applications, such as in making artificial muscles, controlled drug deliv-
ery, biosensors, contact lenses, wound dressing and super-absorbents
[9,12]. In recent years, hydrogels have emerged as a potential candidate
that competes, effectively with many of the existing smart functional
materials used for innumerable applications. Further still, the ever-
growing spectrum of functional monomers and macromeres widen its
applicability [4,9].
The research on this subject is found to be enormously expanding in
the broad spectrum of scientific areas. In view of this, a number of
were examined in order to give an overview of the various aspects cov-
ering the growing multidisciplinary fields of research on hydrogels. An
innovated category of the recent generation of hydrogels, revolution-
ized in the diverse fields (drug delivery, electrical conduction, purifica-
tion of water, agricultural and de-contamination of organic waste)
were majorly focused in this review article. These include superabsor-
bent hybrid hydrogels, protein hydrogels, conducting polymer
hydrogels, polysaccharide-based polymeric hydrogels, hydrogels
based on synthetic polymers, bio-polymer-based hydrogels for the de-
contamination of organic waste. In addition, classification of hydrogels,
based on their cross-linking and physical states were presented with
some great details. Fig. 1 shows the classification of hydrogels based
on preparative (physical or chemical cross-linking) route and physical
properties.
2. Hydrogels classification
2.1. Classification based on cross-linking
Hydrogels can be classified into many ways. However, as the
hydrogels are basically constructed by cross-linking networks, hence,
based on cross-linking they are classified into two categories: (a) phys-
ically cross-linked or self-assembled hydrogel and (b) chemically cross-
linked hydrogel [13,14]. Various types of chemical and physical
hydrogels were prepared with natural/synthetic polymers and they
were used in miscellaneous applications (Table 1).
2.1.1. Physically cross-linked hydrogels
Physically cross-linked hydrogels or reversible gels have gained sig-
nificance due to their relative ease of production and the advantage of
not using cross-linking agents during their synthesis protocol. Dissolu-
tion of physically cross-linked gels is prevented by physical interactions,
which exist between different polymer chains [13]. The selection of hy-
drocolloid type depends on concentration and pH can lead to the forma-
tion of a broad variety of gel textures and is currently an area receiving
considerable attention, in the food, pharmaceutical and biomedical ap-
plications because the use of cross-linking agents is generally avoided
[13,14]. The various methods reported in the literature for obtaining
physically cross-linked hydrogels are:
a) Freeze-thawing
Physical cross-linking can be achieved using repetitive freeze-thaw
cycles. This mechanism involves the formation of microcrystals in the
structure due to freezing and thawing. Poly(vinyl alcohol) (PVA)
hydrogels prepared by freeze-thawing is a popular example. These
hydrogels are inter-connected by hydrogen bonding, exhibit more po-
rous, spongy, rubbery and higher elastic properties than PVA hydrogels
fabricated by other methods [40–42]. Nowadays, these gel matrices
960 K. Varaprasad et al. / Materials Science and Engineering C 79 (2017) 958–971

Fig. 1. Hydrogels and their classifications.

have been broadly implemented in biotechnology fields, especially in c) Ionic interaction

molecules (protein, peptides) [40] and whole cell immobilization [43].
b) Stereocomplex formation
In recent years, hydrogels have been generated for drug delivery sys-
tems that are based on stereo complex formation. The major advantage
of this system is that a hydrogel can be easily formed by dissolving each
product in water and mixing the solution. One best example that ex-
hibits good stereo complex properties is PLA. The ability of PLA to
form stereo complexes was first described by Tsuji et al. [44,45]. One
significant limitation of stereo complexation is, however, the relatively
restricted range of polymer compositions that can be used.
Ionic polymers cross-linked by the addition of di- or tri-valent coun-
ter ions result in hydrogel systems that fall in this category. This method
underlies the principle of gelling a polyelectrolyte solution with multi-
valent ions of opposite charge. Examples of the hydrogels that belong
to this category are: chitosan-glycerol phosphate salt [46] and poly-
[di(carboxylatophenoxy) phosphazene] calcium salt [47].
d) H-bonding
Physically cross-linked gel-like structures can be prepared via hy-
drogen bonding interactions. The best example of such hydrogel is the

Table 1
Various types of chemical and physical hydrogels.

Cross link Polymers Applications References

Physically cross-linked or Freeze-thawing Poly(vinyl alcohol) (PVA) Therapeutic applications [15]

self-assembled hydrogel PVA/chitosan, PVA/starch, Tissue engineering [16]
PVA/gelatin
Stereocomplex Dextran, poly(lactic acid) Drug delivery [17,18]
formation Poly(ethylene glycol) Biomedical and pharmaceutical [19]
Ionic interaction Cellulose microfibrils Drug delivery [20]
Chitosan Antigen delivery [21]
H-bonding Hyaluronic acid Drug delivery [22]
Cyclodextrin, polypseudorotaxane biomedical [23]
Maturation Alginate capsules Cartilage tissue [24]
(heat-induced Hyaluronic acid Soft tissue engineering, cell scaffold, regenerative medicine [25]
aggregation) and cartilage repair
Chemically cross-linked hydrogel Chemical cross-linking Whey protein – [26]
Poly(ethylene glycol) Biomedical [27]
Grafting Chemical Chitosan-cellulose Agiculture and horticultural [28]
grafting Poly(ε-caprolactone), Tissue engineering [29]
poly(ethylene glycol)
Radiation Carboxymethyl cellulose, styrene Water purification [30]
grafting sulfonate
N-Vinylcaprolactam, Chitosan Drug delivery [31]
Radical polymerization Kolliphor Antibacterial [32]
Poly(ethylene glycol)methyl ether Antifouling [33]
methacrylate
Condensation reaction Β-Cyclodextrin Controlled delivery [34]
Cellulose nanofiber Advanced [35]
Enzymatic reaction Poly(ethylene glycol) methacrylate Bio catalysis and tissue engineering [36]
Chitosan Wound dressing and packaging [37]
High-energy radiation Poly(oligo(propylene glycol) biomedical [38]
methacrylate)
Poly(vinyl methyl ether) Biological [39]
 K. Varaprasad et al. / Materials Science and Engineering C 79 (2017) 958–971
formation of hydrogen-bond CMC(carboxymethyl cellulose) network
by dispersing CMC in 0.1 M HCL [48]. In this process the sodium ions
were replaced in CMC by hydrogen in the acid.
e) Maturation (heat-induced aggregation)
Maturation is a heat-induced aggregation process that results in hy-
drogel formation with precisely structured molecular dimensions. The
best example of this hydrogel system is the heat-induced gelation of
gum arabic. The phenomenon is observed due to the aggregation of
the proteinaceous components present in gum arabic, induced by ther-
mal treatment. Due to this aggregation, an increase in the molecular
weight occurs subsequently forming a hydrogel, with improved me-
chanical properties and water binding capability [49,50].
2.1.2. Chemically cross-linked hydrogels
In chemically cross-linked hydrogels, covalent bonds exist between
different polymer chains. Therefore, they are stable and cannot be dis-
solved in any solvents unless the covalent crosslink points are cleaved
[14]. The design flexibility of a physically cross-linked hydrogel is re-
stricted, due to the difficulty in decoupling the variables, such as: gela-
tion time, internal network pore size, chemical functionalization and
degradation time [13]. In contrast, chemical cross-linking results in a
network with a relatively high mechanical strength and depending on
the type of the chemical bonds in the building blocks and the crosslinks,
relatively extended degradation times can occur. The various methods
reported in the literature for obtaining chemically cross-linked
hydrogels are:
a) Chemical cross-linking
In chemical cross-linked hydrogels, cross-linkers, such as: glutaral-
dehyde, epichlorohydrin, adipicacid dihydrazide and polyaldehydes,
etc., are widely used to obtain cross-linked hydrogel networks of vari-
ous synthetic and natural polymers. Further, covalent linkages between
polymer chains can be established by the reaction of functional groups,
such as: an amine-carboxylicacid or an isocyanate-OH/NH2 reaction, or
by Schiff base formation, with complementary reactivity [51]. Hydrogel
composites, based on xanthan and PVA were cross-linked with epichlo-
rohydrin [52].
b) Grafting
Preparation of hydrogels, based on grafting, involves the polymeri-
zation of a monomer on the backbone of a preformed polymer. Depend-
ing on the type of activation initiator, grafting can be classified as
chemical grafting or radiation grafting.
(i) Chemical grafting
In chemical grafting, macromolecular backbones are activated by the
reaction of a chemical reagent. Grafting of acrylic acid (AA) onto granu-
lar maize starch in aqueous medium initiated by ceric ion is an example
of this system [53].
(ii) Radiation grafting
Grafting initiated by the use of high energy radiation, such as gamma
and electron beam, is named as radiation grafting. Grafting of carboxy-
methylcellulose (CMC) with acrylic acid in the presence of electron
beam irradiation, in aqueous solution is an example for radiation
grafting. The electron beam was used to initiate the free radical poly-
merization of acrylic acid on the backbone of CMC [54].
c) Radical polymerization
Chemically cross-linked gels can also be obtained from low-molecu-
lar-weight monomers in the presence of a cross-linking agent by radical
961
polymerization. This is one of the most widely used methods for the
preparation of hydrogels. This is a very efficient system that results in
the rapid formation of the gel, even under mild conditions. Example
for this system is hydrogel fabrication from the free radical initiator:
ammonium persulfate (APS) or potassium persulfate (KPS) [55–57].
d) Condensation reaction
Hydrogels formed through condensation reactions belongs to this
category. In general, the hydrogels involving hydroxyl groups/amines
with carboxylic acids or their derivatives are used for the preparation
of this type of hydrogels. The best example of these condensation reac-
tions was described by De Nooy et al. via the Passerini and Ugi conden-
sation reactions [58,59]. This Passerini condensation yields hydrogels
with ester bonds in their crosslinks. In this typical process, a carboxylic
acid and the carbonyl compound (aldehyde or ketone) are condensed
with an isocyanide, in order to yield α-(acryloxy) amide. In the Ugi con-
densation procedure, an amine is added to this reaction mixture, finally
yielding α-(acrylamino) amide. The hydrogel of this type, typically con-
tains amide bonds in their crosslinks.
e) Enzymatic reaction
A novel hydrogel concept, based on enzymatic reaction can
form hydrogels. Sperinde et al. [60], published an interesting
method using an enzyme to synthesize PEG-based hydrogels. In their
approach, a tetrahydroxy PEG was functionalized with glutaminyl
groups (PEG-Qa). PEG networks were then formed by the addition of
transglutaminase to aqueous solutions of PEG-Qa and poly(lysine-co-
phenylalanine). This enzyme catalyses and yields an amide linkage be-
tween the polymers by the reaction between the γ-carboxamide
group of the PEG-Qa and the ε-amine group of lysine [60].
f) High-energy radiation
Unsaturated compounds can be polymerized by using high-energy
radiation such as gamma (γ) or electron beam radiations. On exposure
to γ or electron beam radiation, water-soluble polymers get derivatized
with vinyl groups to form radicals on the polymer chains by the homo-
lytic scission [61,62]. Further, high energy radiation facilitates water
molecules to form hydroxyl groups that can attack polymeric chains,
resulting in the formation of microradicals. Recombination of these
microradicals on different chains leads to the formation of covalent
bonds, resulting in a cross-linked structure. The advantage of this meth-
od is that the process can be done in water under mild conditions (room
temperature and physiological pH) without using toxic cross-linking
agents. However, a disadvantage is that the irradiation results in forma-
tion of C\\C crosslinks leading to non-biodegradable gels [51]. Examples
for this category includes, formation of poly(viny1 methyl ether)
(PVME) and poly(N-isopropyl acrylamide) (PNIPAAm) hydrogels by
using high energy γ irradiation [63,64].
2.2. Classification based on physical state
Recently, the development of hydrogels with significant physical
properties has attracted a lot of interests in biomedical applications,
due to their unique characteristics, such as their swelling and diffusion
characteristics. Principally, their three-dimensional microstructure
plays a vital role in several fields because this microstructure is respon-
sible for the stabilization of non-extracellular and extracellular matrices.
Polymeric hydrogels have soft tissue-like elastic, non-toxic, biodegrad-
able and bio-comparable properties with stimulus sensitivity. Hence
are widely used in biomedical applications, including drug delivery,
self-healing, smart surfaces, actuators, sensors, scaffolds, tissue engi-
neering, diagnostics, immobilization, separation and blood compatible
coating of medical implants, etc. [65–67]. These properties depend
mainly on hydrogels composition. Owing to their composition
962 K. Varaprasad et al. / Materials Science and Engineering C 79 (2017) 958–971
Fig. 2. Physical properties of hydrogels.
variations, hydrogels are mainly classified into three types for biomedi-
cal applications, based on physical properties (Fig. 2). They are (a) solid
(b) semi-solid and (c) liquid hydrogels.
2.2.1. Solid hydrogels
Solid hydrogels are one of the probable candidates as they can mimic
the physical, chemical, electrical and biological properties of most bio-
logical tissues by mimicking the complex tissue architecture and pro-
vide the essential cellular microenvironment. Furthermore, they are
beneficial in facilitating the formation of functional tissues [13,68,69].
Solid hydrogels have strong cross-linked network structure with
ionic or covalent cross-linkers and they are solid in nature at room tem-
perature, but can swell in water, buffer solutions and biological fluids.
Due to these specific properties, they can be used for the preparation
of hydrogels for biomedical and environmental and ecological applica-
tions. In order to enhance their applicability in advanced (ethnological
and medical) applications, a number of researchers introduced inorgan-
ic metals. Since inorganic materials can easily functionalize with bioma-
terials and these materials provide significant optical, electrical and
magnetic properties, these characteristics make them attractive in the
biomedical field [57].
Since the emerging approach (to reinforce polymeric hydrogels and
include multiple functionalities) focuses on the incorporation of nano-
particles inside the polymeric hydrogels, a wide range of micro/nano-
particles, such as carbon-based, polymeric, ceramic and metallic
nanomaterials were integrated within the hydrogel networks in order
to obtain nanocomposites with superior properties and tailored func-
tionality [70]. Shen et al., [71] reported graphene oxide-based hydrogels
for possible drug release applications. In their study, they reported that
the hydrogels mechanical properties are greatly improved by the addi-
tion of graphene oxide and hydrogel's crosslink density is increased. The
carbon nanotubes (CNTs) reinforced nanocomposites can be used for
electrically conductive tissues, such as muscle, nerve and cardiac tissues.
In a preliminary study, methacrylate gelatin was reinforced with multi-
wall COOH-functionalized CNTs in order to fabricate hybrid nanocom-
posite hydrogels [72]. Many researchers have reported several natural
and synthetic polymer-based temperature-sensitive and biodegradable
hydrogels for drug delivery application and the inactivation of bacterial
activity [55,73–77]. In their report, they used silver, gold, nano-
zincoxide and curcumin to fabricate functional solid hydrogels for bio-
medical applications, particularly, as wound dressing scaffolds. The sig-
nificance of silver, gold, nano-ZnO and curcumin as antimicrobial agents
is well known [57,78–87]. These types of hydrogel systems provide
unique properties that address some of the challenges in biology, med-
icine and material science.
Hybrid polyacrylamide/bacterial cellulose nanofiber clusters
hydrogels with high strength, toughness and recoverability were syn-
thesized. These hybrid gels were observed to exhibit superior mechan-
ical properties, which could offer a great promise as biomaterials such as
bone and cartilage repair materials. The polyacrylamide chains and bac-
terial cellulose nanofiber clusters are mainly contributed to the superior
mechanical properties of hybrid hydrogels [88].
Hydrogels have frequently been studied for myocardial tissue engi-
neering as bioactive substances that mimic biochemical and biome-
chanical microenvironment in order to provide a supportive matrix
for cell delivery. A suitable hydrogel scaffold based on gelatin-collagen
and bioactive glass nanoparticles were designed for myocardial tissue
engineering. The hydrogel scaffold was observed to induce differentia-
tion in Human endometrial stromal cells toward endothelial lineage
and promotes angiogenesis via increasing vascular endothelial growth
factor secretion level [89].
Degradable UV-crosslinked hydrogel for the controlled release
of triclosan that finds applications in drug delivery and the long-term
antibacterial effect was developed from acryloyl chloride-modified
 K. Varaprasad et al. / Materials Science and Engineering C 79 (2017) 958–971
polylactide-poly(ethylene glycol)-polylactide block copolymer
[90]. Hydrogels based on UV-curable quaternary ammonium
polyethyleneimine and AgNO3 were found to have impressive biocidal
properties. These hydrogels not only enhanced the antimicrobial proper-
ty against adherent bacteria but also led to the inhibition of bacterial
growth in suspended culture via the long-term release of Ag/Ag+ to
the surrounding media. These hydrogels are potentially useful as antimi-
crobial agents in a wide variety of applications [91].
2.2.2. Semisolid hydrogels
Semisolid hydrogels have strong adhesive interactions with interfa-
cial (van der Waals, hydrogen bonds and electrostatic) forces and soft
tissue networks. This characteristic is highly useful for the prolonged
drug delivery and effective dosage applications in biomedical filed,
such as buccal, ocular, rectal, vaginal, nasal, and sublingual routes [92].
Due to their bio-adhesive properties, these hydrogels can be termed as
bio-adhesive or muco-adhesive hydrogels.
These type of hydrogels are prepared with two types of materials, of
which, at least one material should possess biological nature (plant
gum, polycarbophil, carbopol, hydroxypropylcellulose and poly(N-
vinyl pyrrolidone) (PVP) [92,93]) and the selecting polymer materials
should be of high molecular weight ≥ 100, which improves the adhesive
nature with wetting, absorption and de-absorption, degree of cross-
linking and the flexibility of the hydrogels for biomedical applications.
Due to the presence of biological materials, the hydrogel complex has
bio adhesion nature with good wetting, absorption and de-absorption
properties. Tangri et al. [94] reported the significance of the muco-adhe-
sive hydrogel systems and their importance in oral drug delivery appli-
cations in biomedicine. In their study, they discussed the mechanism of
muco-adhesion (interaction of polymers) and their capacity for
prolonged drug delivery applications and the importance of polymer se-
lection (high molecular weight, anionic molecules) in order to improve
the muco-adhesion property in the hydrogels.
In the last two decades, important and significant efforts have been
made to develop muco-adhesive hydrogels, based on the self-assembly
of various biological peptides and natural muco-adhesive polymers for
biomedical applications with a focus on tissue regeneration [95,96].
These hydrogels self-assembled structures change the fibrillary struc-
ture at specific conditions. However, based on hydrogel's hydrophobic
and hydrophilic natures, they can be used in several possible applica-
tions. Singh and his co-workers reported sterile muco-adhesive
hydrogels for drug delivery applications [97]. These hydrogels were
synthesized with natural polysaccharide sterculia gum and
poly(vinylprrolidone) (biological in nature), which provide biocompat-
ible muco-adhesive character to the hydrogel, for effective drug delivery
applications. Muco-adhesive hydrogels have strong adhesive capability,
utilizing interfacial forces with soft tissue networks. This characteristic
is highly useful for prolonged drug delivery and effective dosage appli-
cations in the biomedical filed, such as buccal, ocular, rectal, vaginal,
nasal and sublingual routes etc. [96,98]. Recently, a new development
in hydrogel technology has been attempted by using starch
nanocrystals based hydrogel for transdermal application. Bakrudeen et
al., in their work applied a strategy which involved initial preparation
of starch nanocrystals. Latter, the as-prepared starch nanocrystals are
used as a drug carrying filler material in the hydrogel formulations
with the care of different polymer matrices for formulating a complete
transdermal patch [99].
2.2.3. Liquid hydrogels
Liquid hydrogels, at the room temperature, are liquid in phase, but at
a specific temperature, they have a soft tissue-like elastic phase with
good functionality [100–104]. This self-assembled property can play
key roles in future biomedical applications [101,105]. Liquid hydrogels
are very attractive in respect to their unmatched biocompatibility, func-
tion-ability and ease of synthesis as well as the possibility of the self-ad-
justment of their network (pore sizes), according to environmental
963
conditions [100]. The main advantages of this liquid hydrogels are (a)
organic, inorganic, drug, proteins and cells can easily be incorporated
in the hydrogels and (b) without any surgical procedures, it can be in-
jectable (for in-vivo applications) into the living systems, using injec-
tion route to target sites, since it has highly hydrophilic properties
[106–109]. These properties make them attractive in cell biology and re-
generative medicine and biomedical applications [110]. These liquid-
based hydrogels should have good functionality (biodegradation, drug
and natural proteins) in the molecules, biocompatible (allow cell adhe-
sion, migration, proliferation and good porosity for hydration/dehydra-
tion) in order to permit nutrient and waste product flow, which
improves the hydrogels applicability in potential biomedical applica-
tions [111–116]. Xu et al. have reported on injectable biodegradable
hydrogels for cardiac regeneration [117]. In their study, the combination
of thiolated collagen and multiple acrylate containing oligo(acryloyl
carbonate)-b-poly(ethylene glycol)-boligo(acryloyl carbonate) hydro-
gel materials improved the physiological conditions of patients and
they have good functionality for a functional cardiac regeneration.
Wan et al., made a graphene oxide-based hydrogels [118]. In their
study, they reported that due to graphene oxide strong hydrophobic
and hydrogen bonding interaction, the hydrogels shows excellent anti-
bacterial capabilities. Gaudio and his co-workers reported high-
mannuronic alginate hydrogels and their in-vivo applications [119].
However, their results suggest that the hydrogels developed were use-
ful for wound dressing in dermal wound healing.
Furthermore, injectable (self-assembled) hydrogels have greatly
attracted attention in the biomedical field, due to their physical (liquid)
properties, self-adjustability of their pore sizes and good functionality.
These hydrogels are soft tissue, e.g. elastic materials that can minimize
the mechanical frustration, damage the surrounding living systems
and they are excellent cell transporters. Recently, researchers have re-
ported the possibility of biocompatible hydrogels with different bioac-
tive polymers in order to control the mechanical and functional
properties for tissue regeneration and biomedical applications [117,
120]. Hydrogels are prepared with combination of several polymers,
monomers and cross-linkers (with/without), which provides new func-
tional properties for the recent applications.
The addition of oligo(peptides) is unique strategy because it allows
hierarchical self-assembly of peptides. Based on this strategy, re-
searchers have succeeded in developing a hydrogel of pluronic F-127
(PF127) which can undergo gelation at the physiological temperature
and retain their gel integrity with extended incubation. This modifica-
tion is an advent to encompass long-term drug delivery and cell cultur-
ing [121]. Recently a thixotropic injectable hydrogel using a
polyampholyte and nanosilicate has been developed for tissue engi-
neering applications in regenerative medicine. The polyampholyte
could be transformed into a hydrogel by mixing with nanosilicates. It
was observed that the polyampholyte exhibits excellent post-thaw
cell survival. These gels with tunable mechanical properties can be
injected into defect sites to form scaffolds for cell growth and tissue re-
pair, and they do not need additional seeding of cells prior injection,
thus eliminating the need for cell harvesting and cell maintenance.
This is a distinct system in which cells can be cryopreserved until before
usage [122].
Skin is the largest organ in the human body. Due to its significant
clinical need, convenient access, and thin construction, skin has been
at the forefront of engineered tissues. Hydrogels are increasingly used
to repair skin defects. A novel smart injectable hydrogel prepared
from microbial transglutaminase and human-like collagen was found
sensitive to temperature and/or enzymes. These hydrogels are aimed
for potential application as soft materials for skin tissue engineering
[123]. Very recently, Kakkar et al., has fabricated keratin-silica hydrogel
for biomedical applications. Keratin-silica hydrogel was biocompatible
with fibroblast cells and can act as a suitable dressing material [124].
Poloxamer 407/188 binary thermosensitive hydrogels as delivery sys-
tems for delivering ropivacaine, was investigated for their use in
964 K. Varaprasad et al. / Materials Science and Engineering C 79 (2017) 958–971
Fig. 3. Hydrogels and their significance in their various fields of applications.
infiltrative local anesthesia applications on the treatment of post-oper-
ative pain [125].
3. Recent development in miscellaneous application fields
From time-to-time, many scientists and the engineers strive to tack-
le important challenges in the field of hydrogel, which give rise to the
emergence of many developments (Fig. 3). Recent developments ad-
dress critical needs, which include, however not limited to, the follow-
ing spectrum of hydrogels.
3.1. Superabsorbent hybrid hydrogels
Superabsorbent polymers as hydrogels attracts and retains extraor-
dinary large amounts of water or aqueous solution [126]. These
hydrogels can imbibe deionized water as high as between 1000 and
100,000% (10–1000g/g), whereas the absorption capacities of common
hydrogels are not N 100% (1g/g) [127]. Seraphim et al. [128] did report
on biocompatible, flexible superabsorbent hydrogels with tuned prop-
erties that are useful for tissue regeneration applications, which were
prepared by the one-pot synthesis (photo polymerization) method.
Yang et al. [129] reported on superabsorbent polymers suitable for agri-
cultural applications. In their study, they investigated the effects of
hydrogels on moisture distribution throughout infiltration and evapora-
tion under the specific condition of point source irrigation by applying
superabsorbent hydrogels to the middle layer of the soil root zone.
3.1.1. Raw materials
Varieties of monomers, mostly acrylics are employed to prepare su-
perabsorbent polymers. Acrylic acid and its sodium or potassium salts
and acrylamide are most often, used in the production of superabsor-
bent polymers.
3.1.2. Preparation methods
The production of super absorbent hybrid hydrogels is usually done
via inverse micro-emulsion, free radical precipitation, micro-emulsion
polymerization methods and by self-assembling of the polymeric chains
in an aqueous environment [130].
3.1.3. Applications
1. Due to their outstanding water absorption capacity, superabsorbent
hybrid hydrogels can (a) reduce irrigation water consumption, (b)
improve fertilizer retention in soil and (c) lower death rate of plants
and increase plant growth. It is well reported that superabsorbent
hydrogels are used as water-saving materials for the renewal of dry
and desert environments [131,132].
2. The existence of pollutant in the environment contaminates waste
water to a great extent and this causes serious environmental prob-
lems in many parts of the world. Superabsorbent hydrogels are
employed for removing and separating toxic heavy metal ions and
dyes through adsorption, as their structure includes \\OH, \\NH2,
\\CONH2, \\COOH and \\SO3 groups, which are available for the
activation and modification [12] of hydrogels and their properties
[130]. For example, polyacrylamide/gum ghatti/polyaniline
 K. Varaprasad et al. / Materials Science and Engineering C 79 (2017) 958–971 965

interpenetrating hydrogel network displayed excellent material bioelectronics, energy storage devices and as glucose enzyme biosen-
properties for the removal of malachite green dye from the polluted sors with high sensing speed and sensitivity applications [134].
water [133]. 3. CPHs have promising applications in lithium-ion battery technology due
3. Special hydrogels are superabsorbent materials and they are widely to their excellent electronic and electrochemical properties. For instance,
employed as hygienic materials, particularly disposable diapers and CPHs can be used to address the challenges faced by next-generation
lady napkins where they can capture secreted liquids, e.g., blood high capacity alloy-based anodes, such as silicon, germanium [142].
and urine etc. [5]. 4. CPHs are a special class of polymeric hydrogels with potential ad-
4. Drug delivery, targeted drug delivery, and nano/controlled drug de- vanced application in bio-active electrode coating, actuators and tis-
livery are possible with the use super absorbent hybrid hydrogels. sue engineering filed [143–145]. Another important application has
been found in biosensors, which integrate biological sensing ele-
3.2. Conducting polymer hydrogels
ments, such as enzymes, antibodies, nucleic acids, cells, etc. with an
electronic transducer equipped with an electronic amplifier [142].
Conducting polymer hydrogels (CPHs) represent a unique class of
5. CPHs possess a number of advantages, such as providing improved
materials that synergize the advantageous features of both the
electrode interface between the electronic and ionic transport
hydrogels and organic conductors. Conducting polymer hydrogels pro-
phases, a possibility of casting into different, complex and flexible
vide an excellent interface between the electronic-transporting (elec-
shapes and the possibility for the preparation of micro-patterns by
trode) and the ionic-transporting phases (electrolyte), between
ink-jet printing or spray coating [141].
natural and synthetic biological systems and between soft and hard ma-
terials. As a result, conducting polymeric hydrogels demonstrated
3.3. Polysaccharide-based natural hydrogels
promising results for a broad range of recent applications, ranging
from energy storage devices, such as biofuel cells and super capacitors,
Polysaccharides are another class of polymeric materials that were
to molecular and bioelectronics and medical electrodes [134]. CPHs
largely used to stabilize the formed nanoparticles and hydrogels devel-
have been shown to provide excellent process ability and can be easily
opment. Of the numerous polymers that have been proposed for the
cast into thin films and any desired shapes at its gelation stage. CPHs
preparation of several hydrogels, polysaccharides have some excellent
can also be ink-jet printed or screen printed into micro-patterns [134].
properties which make the polymer group, the longest-standing as
Hydrogels based on conducting polymers, combine the several char-
well as widest-ranging knowledge in terms of advanced bio-medical
acteristics of polymeric hydrogels with the electrical and optical charac-
applications, such as non-toxicity (monomer residues are likewise not
teristic of metals or semiconductors, thus offering an array of features,
harmful to living systems health); water solubility/high capacity for
such as intrinsic 3-D micro structured conducting frameworks that pro-
swelling, induced by simple chemical modifications and a wide variety
motes the transport of charges, ions and molecules [135].
of chemical structures [146]. Furthermore, polysaccharides are biocom-
patible, biodegradable, bio-stable, abundant and susceptible of enzy-
3.2.1. Raw materials
matic digestion in the human body. Functionality (biodegradability,
Polyaniline (PANii), polypyrrole (PPy) and polythiophene (PTh)
biocompatibility) is especially useful for the release of drugs at a certain
structures are some suitable raw materials.
time and/or at a certain site in the body [147]. Xu et al., [148] succinctly
reviewed and explained the biocompatibility and biodegradability of
3.2.2. Preparation methods for conducting polymeric hydrogels
hydrogels based on natural polysaccharides. They have significant pH
The synthetic routes toward conducting polymeric hydrogels in-
sensitivity; it helps to control the release of proteins in the simulated in-
clude, synthesizing a conducting polymer/monomer within a three-di-
testinal medium. In these studies, they reported a novel biocompatible
mensional network of hydrogel [134]. Through these methods, non-
polysaccharide-based self-healing hydrogels [149]. Due to its superior
conductive hydrogels can be converted into conducting hydrogels via
self-healing, non-toxic, good mechanical and biocompatible properties,
in-situ polymerization technique of the Electrically Conductive Poly-
they are used for cell/drug delivery applications.
mers (ECPs) into the preformed hydrogel three-dimensional network.
Nowadays, the polysaccharide is being modified in order to obtain
Lately, Lira et al. employed an electrochemical polymerization method
novel biomaterial for controlled drug delivery and as a support material
for the preparation of semi-interpenetrating networks of PANi/PAAM
for gene delivery, cell culture and tissue engineering [150]. In addition,
CPHs and tested their possible applications as electrochemically-con-
the adaptability of their chemical network structures allows develop-
trolled drug delivery device [135]. Tang et al. developed poly(acrylate-
ment of advanced functionalized materials which can meet a multiplic-
aniline) based conducting hydrogels by employing in-situ polymeriza-
ity of requirements. The advanced biomedical region, the degradation of
tion procedure [136,137]. The first step includes the preparation of
natural polymers into physiological metabolites creates them tremen-
cross-linked polyacrylamide hydrogel in powder form, followed by in-
dous candidates for a wide range of advanced applications, including re-
situ polymerization of absorbed aniline in the swollen hydrogel powder
generative medicine [146]. Developed from natural, renewable,
by employing potassium persulfate as an initiator.
nontoxic and biodegradable sources, polysaccharide-based hydrogels
Furthermore, conducting polymer hydrogels (CPHs) has been pre-
are justifiably viewed as ‘ecologically-friendly’ products [146].
pared by various methods, such as the use of electrically conductive
polymers nanoparticles encapsulated into the three-dimensional hy-
3.3.1. Raw materials
drogel network [138,139]. Recently, a few novel conducting hydrogels
These include alginate, chitosan, gelatin, carrageenan, gellan gum,
were developed based on only one material, such kind of materials
guar gum, pectin, cellulose, agarose and xanthan gum, etc.
(e.g., polyaniline (PANi), polypyrrole (PPy), polythiophene (PTh), etc.)
as the continuous phase (conducting polymeric hydrogels) [140].
3.3.2. Preparation methods
Polysaccharides hydrogels are generally synthesized either by
3.2.3. Applications
chemical methods or physical methods. Chemical methods include the
1. Conducting polymer hydrogels (CPHs) have been applied as poten-
chemical cross-linking of the components that are present in the gela-
tial candidates in chemical mimicry of neural networks, implantable
tion feed mixture. Physical hydrogels, made of polysaccharide sources,
electrochemical biosensors, and electro-stimulated drug release, etc.
are prepared by freeze–thaw technique. Polysaccharide hydrogels pre-
[140].
pared from freeze–thaw technique is more biocompatible and biode-
2. CPHs have been proposed as potential conductive flexible electrodes gradable and they have exhibited some improved characteristics over
for super capacitor applications [141] and also it can be used for conventional polysaccharide hydrogels achieved via chemical cross-
966 K. Varaprasad et al. / Materials Science and Engineering C 79 (2017) 958–971
linking. These hydrogels are undoubtedly stabilized mainly by the mul-
tiple inter-chain hydrogen bonds in the junction zones of the polymeric
network [151].
By varying the types of polysaccharides, the nature of soluble
additives and the temperature and duration of freezing, rate of thawing
and the number of refreezing cycles, it is possible to regulate
and modulate the properties of the final gels and their macro- and
micro-structures. Quite a lot of polysaccharides, such as hyaluronic,
carboxymethylated-curdlan, carboxymethylated cellulose, xanthan,
b-glucan, locust bean gum, starch (amylose, amylopectin and their
mixtures), maltodextrins and agarose are capable of forming these
gels [151]. However, in the development of a significant network of
hydrogels, polysaccharide polymers are more attractive than the
synthetic polymers, because of their functional properties (good
hydrophilicity, biodegradation and biocompatibility). As a result of
this property, it has been used in biomedical, environmental and
industrial applications.
3.3.3. Applications
1. Polysaccharides are widely used in various industries applications
like agro-food, paper, cosmetic, textile, biomedical and pharmaceuti-
cal because of their rheological characteristics such as gelling,
viscosifying and stabilization of dispersions. On the other hand, due
to its good tissue compatibility, it has been widely used in the field
of tissue engineering including regeneration of skin, cartilage, bone
and liver, and in the treatment of exuding wounds and in enhancing
the healing process [152,153].
2. Bioactive coatings (e.g. catheter, stent), replacement of nucleus
pulpous and cellular scaffold (artificial organs) are quite evidently
possible with polysaccharide-based hydrogels.
3. Microporous hydrogels have been extensively used for controlled
drug release, blood purification, removing the anionic dyes/metal
ions from polluted water [154], regenerative medicine for cell deliv-
ery and wound dressing materials [78,83].
4. Acidic cellulose–chitin hybrid gel (as novel electrolyte) has been de-
veloped for an electric double layer capacitor.
3.4. Protein-based hydrogels
Nature offers an abundance of structural building blocks for hydro-
gel fabrication that can be derived from a wide range of natural mate-
rials, such as proteins (i.e., silk, collagen, actin and myosin, gelatin,
fibrinogen, elastin, keratin), natural/synthetic polysaccharides (i.e., chi-
tin, cellulose, dextran, amylose and glycosaminoglycan's) or polynucle-
otides (i.e., DNA, RNA) [155]. This wide range of natural materials can
form non-cytotoxic polymeric hydrogels [156]. Among these and in par-
ticular, the protein-based polymeric hydrogels can ape features of the
extra-cellular system and thus have the potential to promote the migra-
tion, growth for tissue regeneration and wound healing. Protein-based
hydrogels are, therefore, also often suitable materials for cell encapsula-
tion [157].
Of the natural polymers, proteins are the most under-rated as well
under-utilized feeds stocks with deference to their advanced industrial
applications. Proteins have been studied as effective starting materials
for the manufacture of several biomaterials, such as films and compos-
ites [158]. In recent years, fibrous protein-based hydrogels have become
popular due to their structural and mechanical similarity with the na-
tive extracellular matrix and their relatively simple process-ability
under mild, cell-compatible conditions [157].
Hydrogels formed by proteins fibrous show close up structural, me-
chanical and chemical similarities with the extracellular matrix, typical-
ly superior biological compatibility and can activate precise cellular
responses. In addition, these hydrogels can be degraded in the body
by proteolytic enzymes. For these reasons, these protein hydrogels are
one of the most versatile materials for tissue engineering [157].
3.4.1. Raw materials
Silk fibroin from spider webs, collagen from skin, keratin as of wool/
hair, bone and tendons, elastin as of elastic tissues, fibrin from blood
clots and resilient from insect tendons are the best examples of proteins.
3.4.2. Preparation methods
Protein-based hydrogels can be prepared through simple free-radi-
cal polymerization method as described by Jayaram et al. [57], where
protein molecules remain in the three-dimensional interpenetrating
hydrogel network.
An efficient way to obtain protein-based hydrogels, is through graft
polymerization of vinyl monomers onto their backbones in the presence
of cross-linkers within different initiator systems [159]. The addition of
vinyl monomers improves the hydrophilic nature of proteins which ac-
cordingly improves the water absorption capacity of the resulting pro-
tein-based hydrogels. To the best knowledge of the authors [158],
collagen and cottonseed proteins are the only proteins which have
been investigated for the synthesis of super absorbent polymer
hydrogels by the graft polymerization technique.
Moreover, proteins are characterized by numerous reactive groups,
which can be used as sites for chemical modifications and cross-link in
order to polymeric structures develop [158]. Food protein hydrogels
are generally obtained using heat treatment, which is problematic for
heat-sensitive active compounds. Hence, cold gelation process is being
adopted. Recently, soy protein hydrogels, using a cold gelation process
have been proven to be a good option for the delivery of active drugs
[160]. This approach consisted of denaturing a soy protein solution by
heating, then cooling to room temperature and addition a Maillard
type cross-linker, i.e., glutaraldehyde/glycerol in the absence or pres-
ence of a salt [161].
3.4.3. Applications
1. Hydrogels prepared from silk fibroin have significant interstitial fluid
support and have compressive moduli between 10 kPa and 50 MPa,
which covers the region of articular cartilage at 0.1–1.3 MPa. Hence,
they are utilized for articular cartilage repairs [162].
2. Elastin-like protein hydrogels have been utilized to promote neurite
out-growth and to better appreciate the property of common poly-
meric hydrogels design parameters on neuronal cultures. Elastin-
like proteins are produced via yielding engineered protein polymers,
recombinant protein synthesis, that is made entirely of amino acids.
3. Elastin-based polymeric hydrogels have shown huge potential for
the advanced engineering of elastic tissues, such as skin, lung and
vasculature. The presence of expandable polymeric fibres in blood
vessels enables the vessels to stretch and relax more than a billion
times during their life time [163].
3.5. Hydrogels based on synthetic polymers
Synthetic polymeric hydrogels constitute a group of materials, used
in numerous disciplines and are still in continuous developing stages for
new and promising applications in biomedical and other sciences. Syn-
thetic hydrogels are usually made from poly(hydroxyalkyl methacry-
lates), Poloxamers, poly(acrylate), poly(acrylic acid), poly(acrylamide)
and poly(methacrylamide) and their derivatives poly(N-vinyl-2-
pyrolidone) and poly(vinyl alcohol), etc. [82,158]. Synthetic hydrogels
exhibit numerous advantages, such as large water absorption capacities
and reasonable gel strength and cost. Synthetic hydrogels differ in their
characteristics due to their various chemical structures, synthesis tech-
niques and water content or cross-linking. It is still possible to design
new hydrogel that fulfils specific functions for specific needs. A change
in chemical composition or even a change in one of the synthesis factors
such as synthesis techniques conditions, cross-linking methods and gels
may lead to new intelligent biomaterials [164].
During the last two decades, natural hydrogels have gradually re-
placed by synthetic hydrogels that have significant capacity of water
 K. Varaprasad et al. / Materials Science and Engineering C 79 (2017) 958–971
absorption and long service life and high gel strength. Fortunately, syn-
thetic polymers usually contain well-defined network structures which
can modified to yield tailor-able degradability and functionality.
Hydrogels can be synthesized from purely synthetic components. In ad-
dition, it is stable in conditions of sharp and strong fluctuating temper-
atures [4].
Some of the synthetic hydrogel systems, e.g. poly(ethylene glycol)
hydrogels are stimuli-sensitive which reacts in the presence of physi-
cal/chemical (bio-logical) agent. As a consequence of their unique prop-
erties, hydrogels employed for these drug releasing systems are called
“smart” or “intelligent gels”. Physical stimuli include solvent, light, tem-
perature, radiation (UV), pressure, magnetic, acoustic/electrical field,
while the chemical and biological stimuli consist of pH, molecular rec-
ognition events and precise ions [164]. It is a known fact that wound
care materials that provide the skin with a moist environment, favour
epithelial cells and tissue reconstruction and therefore, change of dress-
ing is less harmful. This role is excellently played by poly(vinyl alcohol)
(PVA)-based hydrogels, which possess the ability to retain water in the
structure and ensure a prolonged moist environment [164]. These
hydrogels are also soft, transparent and have good permeability–since
oxygen passes through them relatively easily. Furthermore, non-modi-
fied PVA does not adhere well to cells or proteins, which makes it attrac-
tive for new tissue engineering purposes [165,166]. Poloxamers are
amphiphilic non-ionic synthetic [poly(ethylene oxide)-poly(propylene
oxide)] block polymers of hydrophobic propylene oxide and hydrophil-
ic ethylene oxide comprising a central poly(oxypropylene) molecule,
which is flanked on both said by two chains poly(oxyethylene) [167].
Poloxamers have similar chemical structure, except they have a change-
able number of poly(oxypropylene) and poly(oxyethylene) units, and
consequently, they differ in their molecular weight (Poloxamer 188,
and 407) [167]. Due to its hydrophobic and hydrophilic nature, they
are used in pharmaceutical formulations as surfactants, emulsifying
agents, solubilizing agent, dispersing agents, in vivo absorbance en-
hancer and wound care applications [168,169].
3.5.1. Raw materials
Raw materials include poly(N-vinyl-pyrrolidone), anionic and cat-
ionic hydrogels, poly(electrolyte complexes) and poly(vinyl alcohol).
In addition, Poly(hydroxyalkyl methacrylates), poly(acrylate), poly(-
acrylamide) and poly(meth-acrylamide) and its derivatives poly(N-
vinyl-2-pyrolidone) and poly(vinyl alcohol) are also used.
3.5.2. Preparation methods
Synthetic hydrogels may be synthesized in a number of ways. The
polymer engineers can design and synthesize synthetic hydrogels
with modified characteristic such as mechanical strength, bio-degrada-
tion, chemical and biological responses to stimuli, either by chemical or
physical cross-linking methods [4].
Chemically cross-linked hydrogels are three dimensional polymer
networks that have bonds between the chains. Many hydrogels are
products made of covalent bonds (Section 2). These hydrogels can
also be formed directly from hydrophobic monomers. Monomers,
such as vinyl pyrrolidone, methacrylic acid and poly-2-hydroxyethyl
methacrylate form the basis of hydrogel formation and they are mostly
used in the fabrication of contact lenses. Additionally, hydrogel can also
be engineered via the cross-linking of hydrophilic polymer chains.
Among the methods of cross-linking, the utilization of hydrolysis/radia-
tion of hydrophobic polymeric network is very popular [170].
Hydrogels formed from physical interaction are broad class of 3D
biomaterials. These interactions can be formed by crystalline junctions,
hydrogen bonding, phase-separation or other associations. The strength
of the hydrogel depends on the strength of these physical bonds and
their density. Hydrogen bond formation results from the interaction be-
tween a hydrogen atom and an electronegative atom, e.g., oxygen. Al-
though the bond is relatively weak when compared to a covalent
bond, it can still be structurally stable. These hydrogen bonds create
967
crystalline junction points in the polymer chain and translate into hy-
drogel [170].
PVA is an interesting synthetic water soluble polymer that can be
transformed into hydrogels via a variety of mechanisms. PVA can be co-
valently cross-linked to form a hydrogel. Similarly, PVA gel formation
via hydrogen bonds is also very popular. Its derivative hydrogels can
be made via repeated freezing and thawing of PVA solution [127]. This
allows the polymer chains to move into sufficiently close proximity in
order to form the hydrogen bonds and subsequent crystalline junction
points. With the increase in a number of freeze-thaw cycles, tougher hy-
drogel could be produced.
3.5.3. Applications
1. Poly(hydroxyethyl methacrylate) ensures good wound-healing con-
ditions and therefore, it is most widely applied in dressings, especial-
ly burn dressings applications. It is used in contact lenses, drug
delivery and tissue engineering purposes for marrow and spinal
cord cell regeneration and as scaffolds for promoting cell adhesion
and in artificial skin manufacturing, artificial cartilage production ap-
plications [164].
2. PVA vitreous has been employed in a variety of biomedical applica-
tions, including drug delivery, artificial tears, contact lenses, artificial
cell encapsulation and more recently, as nerve cuffs [170]. PVA hy-
drogel applications encompass injectable implants, endo-prostheses
or soft tissue fillers in plastic, cartilage reconstructive, aesthetic sur-
gery, artificial organs, drugs systems and wound dressings, providing
the humid environment that is beneficial for wound healing [171].
3. Poly(ethylene glycol), PEG-based hydrogels are characterized for
their high biocompatibility, lack of toxic influence on the surround-
ing tissue and solubility in water, which make them good candidates
for drug delivery applications [164]. They are used as matrices for cell
delivery for promoting tissue regeneration.
4. Thermosensitive tri-block poly(ethylene-glycol)-poly(ε-
caprolactone)-poly(ethylene glycol) hydrogels formed in-situ, can
be easily applied in several biomedical applications such as cell en-
capsulation, controlled drug delivery and tissue repair. Poly(imide)
(PI) hydrogels and PVA hydrogels has been used in plastic and recon-
structive surgery [164].
5. Polyacrylate (PA) based polymeric hydrogels play a significant role in
advanced biomedical applications in aesthetic corrections, as soft tissue
fillers and augmentation materials. Besides silicone, PAA tops the list of
applications in breast augmentation in Eastern Europe and Asia [164].
6. Poly(urethane) hydrogels are applied as drug carriers, in wound
dressing materials manufacture, artificial kidney membranes, cathe-
ter coating materials and contact lenses [172,173]. Furthermore,
hydrogels made of poly(urethane)/poly(acrylamide) are used for
dressings, artificial muscles, sensor systems and bio-separators.
4. Conclusion and future prospective
Without a doubt, there are a number of significant features of poly-
meric hydrogels that qualifies and allows them to exhibit extraordinary
characteristics, which enables them to be employed as essentials tools
for applications in almost all the fields, such as biomedical, agricultural,
industrial and environmental areas. From time-to-time, significant
modifications are made to revolutionize the field of hydrogels for their
comprehensive applications. In this review, polymeric hydrogels, corre-
sponding to the recent generations of the materials, have been exten-
sively researched and their technical utilizations have been succinctly
discussed. Recent developments (in diverse classifications) of
hydrogels, have revolutionized the present research, in relation to
drug delivery systems, electrical conducting, purification of water, agri-
cultural sector, decontamination of organic waste, etc., and these devel-
opments are presented in this comprehensive review of the different
types of hydrogels such as superabsorbent hybrid hydrogels,
Conducting polymer hydrogels, Polysaccharide-based natural
968 K. Varaprasad et al. / Materials Science and Engineering C 79 (2017) 958–971
hydrogels, Protein-based hydrogels, Hydrogels based on synthetic poly-
mers, Bio-polymer based hydrogel for the decontamination of organic
waste and other hydrogels, their preparations and applications are suc-
cinctly discussed.
For future studies, more attention should be focused in order to meet
the specific requirements of advanced and sophisticated drug delivery
systems. Cross-linked architectures of monomers, pre-polymers and
polymers, would remain as the most preferred delivery device.
“Green”, describes the use of (safe solvents, no solvent at all or nontoxic
cross-linkers) and/or low-energy processing for hydrogel systems. In-
jectable hydrogels that can be safely formed within the body without
the need of surgery, for targeting drug release or tissue engineering de-
velopment of hydrogel functionalization, will undoubtedly, be a wel-
coming convenience for the end users. Realizing the usage
requirements, while limiting the complexity of the hydrogel formula-
tion, will be the main goal for the coming decades. Although, extensive
research is on-going in order to provide new kind of hydrogels for future
necessities, novel conceptual assimilation of hydrogel preparation may
lead to tailored properties, translating its innovative applications in
the diversified fields. Above all, an economical way to improve the effi-
cacy of the hydrogel system will be the most demandingly needed
approach.
Acknowledgements
The author, Kokkarachedu Varaprasad wishes to acknowledge the
Fondecyt Proyecto No 11160073, Programa de Atracción e Inserción
de Capital Humano Avanzado (PAI) Proyecto No 78130211 Conicyt,
Chile, and the Centro de Investigación de Polímeros Avanzados (CIPA),
CONICYT Regional, GORE BIO-BIO PRFC0002. The author MMY acknowl-
edge National Institute of Health/National Cancer Center's Career Devel-
opment Award K22 CA174841.
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