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Materials Science and Engineering C 79 (2017) 958971

Contents lists available at ScienceDirect

Materials Science and Engineering C

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

Review

A mini review on hydrogels classication 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 Investigacin de Polmeros Avanzados, CIPA, Av.Collao 1202, Edicio Laboratorio CIPA Concepcin, 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 scientic research interest which leads to a
Accepted 14 May 2017
dominating path in extending their potential in hi-tech applications. Over the past decades, signicant progress
Available online 15 May 2017
has been made in the eld 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
Classication article summarizes the classication 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 classication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 959
2.1. Classication based on cross-linking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 959
2.1.1. Physically cross-linked hydrogels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 959
2.1.2. Chemically cross-linked hydrogels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 961
2.2. Classication 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 elds. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 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) 958971 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


were examined in order to give an overview of the various aspects cov-
Hydrogels are the cross-linked polymeric materials that have been ering the growing multidisciplinary elds of research on hydrogels. An
playing signicant roles in various elds. Hydrogel came into light with innovated category of the recent generation of hydrogels, revolution-
the establishment of the rst synthetic hydrogels by Wichterle and Lim ized in the diverse elds (drug delivery, electrical conduction, purica-
[1] in 1954. Hydrogels are three-dimensional (3D), insoluble, cross- tion of water, agricultural and de-contamination of organic waste)
linked and tissues like polymer networks that are able to retain a large were majorly focused in this review article. These include superabsor-
amount of water and biological uids in their swollen state. The interac- bent hybrid hydrogels, protein hydrogels, conducting polymer
tion between polymeric chain networks and water or biological uids hydrogels, polysaccharide-based polymeric hydrogels, hydrogels
occur through capillary, osmotic and hydration forces, which are coun- based on synthetic polymers, bio-polymer-based hydrogels for the de-
ter-balanced, causing expansion of chain networks [2]. Such equilibrium contamination of organic waste. In addition, classication of hydrogels,
state of hydrogel depends on the magnitude of these opposing effects based on their cross-linking and physical states were presented with
which determines some inherent properties of the hydrogel, including some great details. Fig. 1 shows the classication of hydrogels based
internal transport, diffusion characteristics, and mechanical strength on preparative (physical or chemical cross-linking) route and physical
[3]. properties.
Over the years, researchers have dened hydrogels in many differ-
ent ways. The most commonly used denition is that the hydrogel is a 2. Hydrogels classication
water-swollen and cross-linked polymeric network, produced by the
simple reaction of one or more monomer/polymer/cross-linker units. 2.1. Classication based on cross-linking
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- Hydrogels can be classied into many ways. However, as the
mensional network, however, will not dissolve in water [4]. In another hydrogels are basically constructed by cross-linking networks, hence,
way, they are dened as polymeric systems that show the capability based on cross-linking they are classied into two categories: (a) phys-
of swelling in water and retaining a signicant fraction (N20%) of ically cross-linked or self-assembled hydrogel and (b) chemically cross-
water inside their 3D structure, without dissolving in water [5]. The linked hydrogel [13,14]. Various types of chemical and physical
terms gels and hydrogels are used interchangeably by food and bioma- hydrogels were prepared with natural/synthetic polymers and they
terial scientists to describe polymeric cross-linked network structures. were used in miscellaneous applications (Table 1).
Gels are dened as a substantially dilute cross-linked system and
these are categorized, mainly as weak or strong depending on their 2.1.1. Physically cross-linked hydrogels
ow behavior in steady-state [6]. In a broader term, hydrogels are a hy- Physically cross-linked hydrogels or reversible gels have gained sig-
drophilic polymeric network of three-dimensionally cross-linked struc- nicance due to their relative ease of production and the advantage of
tures achieved from a class of natural/synthetic polymeric materials that not using cross-linking agents during their synthesis protocol. Dissolu-
absorbs a substantial amount of water. Cross-linking facilitates their in- tion of physically cross-linked gels is prevented by physical interactions,
solubility in water because of the ionic interaction and hydrogen bond- which exist between different polymer chains [13]. The selection of hy-
ing [7]. It also provides the essential mechanical strength as well as drocolloid type depends on concentration and pH can lead to the forma-
physical integrity to the polymeric hydrogels [8]. tion of a broad variety of gel textures and is currently an area receiving
Hydrogels are being applied to food additives, pharmaceuticals, bio- considerable attention, in the food, pharmaceutical and biomedical ap-
medical implants, tissue engineering and regenerative medicines, diag- plications because the use of cross-linking agents is generally avoided
nostics, cellular immobility, cell encapsulation, separation of [13,14]. The various methods reported in the literature for obtaining
biomolecules or cells and barrier materials for the regulation of biolog- physically cross-linked hydrogels are:
ical adhesions, biosensor and biomedical microelectro-mechanical de-
vices [911]. Furthermore, they have been used in diverse a) Freeze-thawing
applications, such as in making articial 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 Physical cross-linking can be achieved using repetitive freeze-thaw
that competes, effectively with many of the existing smart functional cycles. This mechanism involves the formation of microcrystals in the
materials used for innumerable applications. Further still, the ever- structure due to freezing and thawing. Poly(vinyl alcohol) (PVA)
growing spectrum of functional monomers and macromeres widen its hydrogels prepared by freeze-thawing is a popular example. These
applicability [4,9]. hydrogels are inter-connected by hydrogen bonding, exhibit more po-
The research on this subject is found to be enormously expanding in rous, spongy, rubbery and higher elastic properties than PVA hydrogels
the broad spectrum of scientic areas. In view of this, a number of fabricated by other methods [4042]. Nowadays, these gel matrices
960 K. Varaprasad et al. / Materials Science and Engineering C 79 (2017) 958971

Fig. 1. Hydrogels and their classications.

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


molecules (protein, peptides) [40] and whole cell immobilization [43].
Ionic polymers cross-linked by the addition of di- or tri-valent coun-
b) Stereocomplex formation
ter ions result in hydrogel systems that fall in this category. This method
underlies the principle of gelling a polyelectrolyte solution with multi-
In recent years, hydrogels have been generated for drug delivery sys- valent ions of opposite charge. Examples of the hydrogels that belong
tems that are based on stereo complex formation. The major advantage to this category are: chitosan-glycerol phosphate salt [46] and poly-
of this system is that a hydrogel can be easily formed by dissolving each [di(carboxylatophenoxy) phosphazene] calcium salt [47].
product in water and mixing the solution. One best example that ex-
hibits good stereo complex properties is PLA. The ability of PLA to d) H-bonding
form stereo complexes was rst described by Tsuji et al. [44,45]. One
signicant limitation of stereo complexation is, however, the relatively Physically cross-linked gel-like structures can be prepared via hy-
restricted range of polymer compositions that can be used. 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 microbrils 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(-caprolactone), Tissue engineering [29]
poly(ethylene glycol)
Radiation Carboxymethyl cellulose, styrene Water purication [30]
grafting sulfonate
N-Vinylcaprolactam, Chitosan Drug delivery [31]
Radical polymerization Kolliphor Antibacterial [32]
Poly(ethylene glycol)methyl ether Antifouling [33]
methacrylate
Condensation reaction -Cyclodextrin Controlled delivery [34]
Cellulose nanober 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) 958971 961

formation of hydrogen-bond CMC(carboxymethyl cellulose) network polymerization. This is one of the most widely used methods for the
by dispersing CMC in 0.1 M HCL [48]. In this process the sodium ions preparation of hydrogels. This is a very efcient system that results in
were replaced in CMC by hydrogen in the acid. the rapid formation of the gel, even under mild conditions. Example
for this system is hydrogel fabrication from the free radical initiator:
e) Maturation (heat-induced aggregation)
ammonium persulfate (APS) or potassium persulfate (KPS) [5557].

Maturation is a heat-induced aggregation process that results in hy- d) Condensation reaction


drogel formation with precisely structured molecular dimensions. The
best example of this hydrogel system is the heat-induced gelation of Hydrogels formed through condensation reactions belongs to this
gum arabic. The phenomenon is observed due to the aggregation of category. In general, the hydrogels involving hydroxyl groups/amines
the proteinaceous components present in gum arabic, induced by ther- with carboxylic acids or their derivatives are used for the preparation
mal treatment. Due to this aggregation, an increase in the molecular of this type of hydrogels. The best example of these condensation reac-
weight occurs subsequently forming a hydrogel, with improved me- tions was described by De Nooy et al. via the Passerini and Ugi conden-
chanical properties and water binding capability [49,50]. sation reactions [58,59]. This Passerini condensation yields hydrogels
with ester bonds in their crosslinks. In this typical process, a carboxylic
2.1.2. Chemically cross-linked hydrogels acid and the carbonyl compound (aldehyde or ketone) are condensed
In chemically cross-linked hydrogels, covalent bonds exist between with an isocyanide, in order to yield -(acryloxy) amide. In the Ugi con-
different polymer chains. Therefore, they are stable and cannot be dis- densation procedure, an amine is added to this reaction mixture, nally
solved in any solvents unless the covalent crosslink points are cleaved yielding -(acrylamino) amide. The hydrogel of this type, typically con-
[14]. The design exibility of a physically cross-linked hydrogel is re- tains amide bonds in their crosslinks.
stricted, due to the difculty in decoupling the variables, such as: gela-
e) Enzymatic reaction
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 A novel hydrogel concept, based on enzymatic reaction can
the type of the chemical bonds in the building blocks and the crosslinks, form hydrogels. Sperinde et al. [60], published an interesting
relatively extended degradation times can occur. The various methods method using an enzyme to synthesize PEG-based hydrogels. In their
reported in the literature for obtaining chemically cross-linked approach, a tetrahydroxy PEG was functionalized with glutaminyl
hydrogels are: groups (PEG-Qa). PEG networks were then formed by the addition of
transglutaminase to aqueous solutions of PEG-Qa and poly(lysine-co-
a) Chemical cross-linking phenylalanine). This enzyme catalyses and yields an amide linkage be-
tween the polymers by the reaction between the -carboxamide
In chemical cross-linked hydrogels, cross-linkers, such as: glutaral- group of the PEG-Qa and the -amine group of lysine [60].
dehyde, epichlorohydrin, adipicacid dihydrazide and polyaldehydes,
f) High-energy radiation
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, Unsaturated compounds can be polymerized by using high-energy
such as: an amine-carboxylicacid or an isocyanate-OH/NH2 reaction, or radiation such as gamma () or electron beam radiations. On exposure
by Schiff base formation, with complementary reactivity [51]. Hydrogel to or electron beam radiation, water-soluble polymers get derivatized
composites, based on xanthan and PVA were cross-linked with epichlo- with vinyl groups to form radicals on the polymer chains by the homo-
rohydrin [52]. lytic scission [61,62]. Further, high energy radiation facilitates water
molecules to form hydroxyl groups that can attack polymeric chains,
b) Grafting resulting in the formation of microradicals. Recombination of these
microradicals on different chains leads to the formation of covalent
Preparation of hydrogels, based on grafting, involves the polymeri- bonds, resulting in a cross-linked structure. The advantage of this meth-
zation of a monomer on the backbone of a preformed polymer. Depend- od is that the process can be done in water under mild conditions (room
ing on the type of activation initiator, grafting can be classied as temperature and physiological pH) without using toxic cross-linking
chemical grafting or radiation grafting. agents. However, a disadvantage is that the irradiation results in forma-
tion of C\\C crosslinks leading to non-biodegradable gels [51]. Examples
(i) Chemical grafting
for this category includes, formation of poly(viny1 methyl ether)
(PVME) and poly(N-isopropyl acrylamide) (PNIPAAm) hydrogels by
In chemical grafting, macromolecular backbones are activated by the using high energy irradiation [63,64].
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 2.2. Classication based on physical state
of this system [53].
(ii) Radiation grafting Recently, the development of hydrogels with signicant physical
properties has attracted a lot of interests in biomedical applications,
Grafting initiated by the use of high energy radiation, such as gamma due to their unique characteristics, such as their swelling and diffusion
and electron beam, is named as radiation grafting. Grafting of carboxy- characteristics. Principally, their three-dimensional microstructure
methylcellulose (CMC) with acrylic acid in the presence of electron plays a vital role in several elds because this microstructure is respon-
beam irradiation, in aqueous solution is an example for radiation sible for the stabilization of non-extracellular and extracellular matrices.
grafting. The electron beam was used to initiate the free radical poly- Polymeric hydrogels have soft tissue-like elastic, non-toxic, biodegrad-
merization of acrylic acid on the backbone of CMC [54]. able and bio-comparable properties with stimulus sensitivity. Hence
are widely used in biomedical applications, including drug delivery,
c) Radical polymerization self-healing, smart surfaces, actuators, sensors, scaffolds, tissue engi-
neering, diagnostics, immobilization, separation and blood compatible
Chemically cross-linked gels can also be obtained from low-molecu- coating of medical implants, etc. [6567]. These properties depend
lar-weight monomers in the presence of a cross-linking agent by radical mainly on hydrogels composition. Owing to their composition
962 K. Varaprasad et al. / Materials Science and Engineering C 79 (2017) 958971

Fig. 2. Physical properties of hydrogels.

variations, hydrogels are mainly classied into three types for biomedi- electrically conductive tissues, such as muscle, nerve and cardiac tissues.
cal applications, based on physical properties (Fig. 2). They are (a) solid In a preliminary study, methacrylate gelatin was reinforced with multi-
(b) semi-solid and (c) liquid hydrogels. wall COOH-functionalized CNTs in order to fabricate hybrid nanocom-
posite hydrogels [72]. Many researchers have reported several natural
2.2.1. Solid hydrogels and synthetic polymer-based temperature-sensitive and biodegradable
Solid hydrogels are one of the probable candidates as they can mimic hydrogels for drug delivery application and the inactivation of bacterial
the physical, chemical, electrical and biological properties of most bio- activity [55,7377]. In their report, they used silver, gold, nano-
logical tissues by mimicking the complex tissue architecture and pro- zincoxide and curcumin to fabricate functional solid hydrogels for bio-
vide the essential cellular microenvironment. Furthermore, they are medical applications, particularly, as wound dressing scaffolds. The sig-
benecial in facilitating the formation of functional tissues [13,68,69]. nicance of silver, gold, nano-ZnO and curcumin as antimicrobial agents
Solid hydrogels have strong cross-linked network structure with is well known [57,7887]. These types of hydrogel systems provide
ionic or covalent cross-linkers and they are solid in nature at room tem- unique properties that address some of the challenges in biology, med-
perature, but can swell in water, buffer solutions and biological uids. icine and material science.
Due to these specic properties, they can be used for the preparation Hybrid polyacrylamide/bacterial cellulose nanober clusters
of hydrogels for biomedical and environmental and ecological applica- hydrogels with high strength, toughness and recoverability were syn-
tions. In order to enhance their applicability in advanced (ethnological thesized. These hybrid gels were observed to exhibit superior mechan-
and medical) applications, a number of researchers introduced inorgan- ical properties, which could offer a great promise as biomaterials such as
ic metals. Since inorganic materials can easily functionalize with bioma- bone and cartilage repair materials. The polyacrylamide chains and bac-
terials and these materials provide signicant optical, electrical and terial cellulose nanober clusters are mainly contributed to the superior
magnetic properties, these characteristics make them attractive in the mechanical properties of hybrid hydrogels [88].
biomedical eld [57]. Hydrogels have frequently been studied for myocardial tissue engi-
Since the emerging approach (to reinforce polymeric hydrogels and neering as bioactive substances that mimic biochemical and biome-
include multiple functionalities) focuses on the incorporation of nano- chanical microenvironment in order to provide a supportive matrix
particles inside the polymeric hydrogels, a wide range of micro/nano- for cell delivery. A suitable hydrogel scaffold based on gelatin-collagen
particles, such as carbon-based, polymeric, ceramic and metallic and bioactive glass nanoparticles were designed for myocardial tissue
nanomaterials were integrated within the hydrogel networks in order engineering. The hydrogel scaffold was observed to induce differentia-
to obtain nanocomposites with superior properties and tailored func- tion in Human endometrial stromal cells toward endothelial lineage
tionality [70]. Shen et al., [71] reported graphene oxide-based hydrogels and promotes angiogenesis via increasing vascular endothelial growth
for possible drug release applications. In their study, they reported that factor secretion level [89].
the hydrogels mechanical properties are greatly improved by the addi- Degradable UV-crosslinked hydrogel for the controlled release
tion of graphene oxide and hydrogel's crosslink density is increased. The of triclosan that nds applications in drug delivery and the long-term
carbon nanotubes (CNTs) reinforced nanocomposites can be used for antibacterial effect was developed from acryloyl chloride-modied
K. Varaprasad et al. / Materials Science and Engineering C 79 (2017) 958971 963

polylactide-poly(ethylene glycol)-polylactide block copolymer conditions [100]. The main advantages of this liquid hydrogels are (a)
[90]. Hydrogels based on UV-curable quaternary ammonium organic, inorganic, drug, proteins and cells can easily be incorporated
polyethyleneimine and AgNO3 were found to have impressive biocidal in the hydrogels and (b) without any surgical procedures, it can be in-
properties. These hydrogels not only enhanced the antimicrobial proper- jectable (for in-vivo applications) into the living systems, using injec-
ty against adherent bacteria but also led to the inhibition of bacterial tion route to target sites, since it has highly hydrophilic properties
growth in suspended culture via the long-term release of Ag/Ag+ to [106109]. These properties make them attractive in cell biology and re-
the surrounding media. These hydrogels are potentially useful as antimi- generative medicine and biomedical applications [110]. These liquid-
crobial agents in a wide variety of applications [91]. based hydrogels should have good functionality (biodegradation, drug
and natural proteins) in the molecules, biocompatible (allow cell adhe-
2.2.2. Semisolid hydrogels sion, migration, proliferation and good porosity for hydration/dehydra-
Semisolid hydrogels have strong adhesive interactions with interfa- tion) in order to permit nutrient and waste product ow, which
cial (van der Waals, hydrogen bonds and electrostatic) forces and soft improves the hydrogels applicability in potential biomedical applica-
tissue networks. This characteristic is highly useful for the prolonged tions [111116]. Xu et al. have reported on injectable biodegradable
drug delivery and effective dosage applications in biomedical led, hydrogels for cardiac regeneration [117]. In their study, the combination
such as buccal, ocular, rectal, vaginal, nasal, and sublingual routes [92]. of thiolated collagen and multiple acrylate containing oligo(acryloyl
Due to their bio-adhesive properties, these hydrogels can be termed as carbonate)-b-poly(ethylene glycol)-boligo(acryloyl carbonate) hydro-
bio-adhesive or muco-adhesive hydrogels. gel materials improved the physiological conditions of patients and
These type of hydrogels are prepared with two types of materials, of they have good functionality for a functional cardiac regeneration.
which, at least one material should possess biological nature (plant Wan et al., made a graphene oxide-based hydrogels [118]. In their
gum, polycarbophil, carbopol, hydroxypropylcellulose and poly(N- study, they reported that due to graphene oxide strong hydrophobic
vinyl pyrrolidone) (PVP) [92,93]) and the selecting polymer materials and hydrogen bonding interaction, the hydrogels shows excellent anti-
should be of high molecular weight 100, which improves the adhesive bacterial capabilities. Gaudio and his co-workers reported high-
nature with wetting, absorption and de-absorption, degree of cross- mannuronic alginate hydrogels and their in-vivo applications [119].
linking and the exibility of the hydrogels for biomedical applications. However, their results suggest that the hydrogels developed were use-
Due to the presence of biological materials, the hydrogel complex has ful for wound dressing in dermal wound healing.
bio adhesion nature with good wetting, absorption and de-absorption Furthermore, injectable (self-assembled) hydrogels have greatly
properties. Tangri et al. [94] reported the signicance of the muco-adhe- attracted attention in the biomedical eld, due to their physical (liquid)
sive hydrogel systems and their importance in oral drug delivery appli- properties, self-adjustability of their pore sizes and good functionality.
cations in biomedicine. In their study, they discussed the mechanism of These hydrogels are soft tissue, e.g. elastic materials that can minimize
muco-adhesion (interaction of polymers) and their capacity for the mechanical frustration, damage the surrounding living systems
prolonged drug delivery applications and the importance of polymer se- and they are excellent cell transporters. Recently, researchers have re-
lection (high molecular weight, anionic molecules) in order to improve ported the possibility of biocompatible hydrogels with different bioac-
the muco-adhesion property in the hydrogels. tive polymers in order to control the mechanical and functional
In the last two decades, important and signicant efforts have been properties for tissue regeneration and biomedical applications [117,
made to develop muco-adhesive hydrogels, based on the self-assembly 120]. Hydrogels are prepared with combination of several polymers,
of various biological peptides and natural muco-adhesive polymers for monomers and cross-linkers (with/without), which provides new func-
biomedical applications with a focus on tissue regeneration [95,96]. tional properties for the recent applications.
These hydrogels self-assembled structures change the brillary struc- The addition of oligo(peptides) is unique strategy because it allows
ture at specic conditions. However, based on hydrogel's hydrophobic hierarchical self-assembly of peptides. Based on this strategy, re-
and hydrophilic natures, they can be used in several possible applica- searchers have succeeded in developing a hydrogel of pluronic F-127
tions. Singh and his co-workers reported sterile muco-adhesive (PF127) which can undergo gelation at the physiological temperature
hydrogels for drug delivery applications [97]. These hydrogels were and retain their gel integrity with extended incubation. This modica-
synthesized with natural polysaccharide sterculia gum and tion is an advent to encompass long-term drug delivery and cell cultur-
poly(vinylprrolidone) (biological in nature), which provide biocompat- ing [121]. Recently a thixotropic injectable hydrogel using a
ible muco-adhesive character to the hydrogel, for effective drug delivery polyampholyte and nanosilicate has been developed for tissue engi-
applications. Muco-adhesive hydrogels have strong adhesive capability, neering applications in regenerative medicine. The polyampholyte
utilizing interfacial forces with soft tissue networks. This characteristic could be transformed into a hydrogel by mixing with nanosilicates. It
is highly useful for prolonged drug delivery and effective dosage appli- was observed that the polyampholyte exhibits excellent post-thaw
cations in the biomedical led, such as buccal, ocular, rectal, vaginal, cell survival. These gels with tunable mechanical properties can be
nasal and sublingual routes etc. [96,98]. Recently, a new development injected into defect sites to form scaffolds for cell growth and tissue re-
in hydrogel technology has been attempted by using starch pair, and they do not need additional seeding of cells prior injection,
nanocrystals based hydrogel for transdermal application. Bakrudeen et thus eliminating the need for cell harvesting and cell maintenance.
al., in their work applied a strategy which involved initial preparation This is a distinct system in which cells can be cryopreserved until before
of starch nanocrystals. Latter, the as-prepared starch nanocrystals are usage [122].
used as a drug carrying ller material in the hydrogel formulations Skin is the largest organ in the human body. Due to its signicant
with the care of different polymer matrices for formulating a complete clinical need, convenient access, and thin construction, skin has been
transdermal patch [99]. at the forefront of engineered tissues. Hydrogels are increasingly used
to repair skin defects. A novel smart injectable hydrogel prepared
2.2.3. Liquid hydrogels from microbial transglutaminase and human-like collagen was found
Liquid hydrogels, at the room temperature, are liquid in phase, but at sensitive to temperature and/or enzymes. These hydrogels are aimed
a specic temperature, they have a soft tissue-like elastic phase with for potential application as soft materials for skin tissue engineering
good functionality [100104]. This self-assembled property can play [123]. Very recently, Kakkar et al., has fabricated keratin-silica hydrogel
key roles in future biomedical applications [101,105]. Liquid hydrogels for biomedical applications. Keratin-silica hydrogel was biocompatible
are very attractive in respect to their unmatched biocompatibility, func- with broblast cells and can act as a suitable dressing material [124].
tion-ability and ease of synthesis as well as the possibility of the self-ad- Poloxamer 407/188 binary thermosensitive hydrogels as delivery sys-
justment of their network (pore sizes), according to environmental tems for delivering ropivacaine, was investigated for their use in
964 K. Varaprasad et al. / Materials Science and Engineering C 79 (2017) 958971

Fig. 3. Hydrogels and their signicance in their various elds of applications.

inltrative local anesthesia applications on the treatment of post-oper- 3.1.1. Raw materials
ative pain [125]. 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-
3. Recent development in miscellaneous application elds bent polymers.

From time-to-time, many scientists and the engineers strive to tack- 3.1.2. Preparation methods
le important challenges in the eld of hydrogel, which give rise to the The production of super absorbent hybrid hydrogels is usually done
emergence of many developments (Fig. 3). Recent developments ad- via inverse micro-emulsion, free radical precipitation, micro-emulsion
dress critical needs, which include, however not limited to, the follow- polymerization methods and by self-assembling of the polymeric chains
ing spectrum of hydrogels. in an aqueous environment [130].

3.1.3. Applications
3.1. Superabsorbent hybrid hydrogels
1. Due to their outstanding water absorption capacity, superabsorbent
hybrid hydrogels can (a) reduce irrigation water consumption, (b)
Superabsorbent polymers as hydrogels attracts and retains extraor-
improve fertilizer retention in soil and (c) lower death rate of plants
dinary large amounts of water or aqueous solution [126]. These
and increase plant growth. It is well reported that superabsorbent
hydrogels can imbibe deionized water as high as between 1000 and
hydrogels are used as water-saving materials for the renewal of dry
100,000% (101000g/g), whereas the absorption capacities of common
and desert environments [131,132].
hydrogels are not N 100% (1g/g) [127]. Seraphim et al. [128] did report
on biocompatible, exible superabsorbent hydrogels with tuned prop- 2. The existence of pollutant in the environment contaminates waste
erties that are useful for tissue regeneration applications, which were water to a great extent and this causes serious environmental prob-
prepared by the one-pot synthesis (photo polymerization) method. lems in many parts of the world. Superabsorbent hydrogels are
Yang et al. [129] reported on superabsorbent polymers suitable for agri- employed for removing and separating toxic heavy metal ions and
cultural applications. In their study, they investigated the effects of dyes through adsorption, as their structure includes \\OH, \\NH2,
hydrogels on moisture distribution throughout inltration and evapora- \\CONH2, \\COOH and \\SO3 groups, which are available for the
tion under the specic condition of point source irrigation by applying activation and modication [12] of hydrogels and their properties
superabsorbent hydrogels to the middle layer of the soil root zone. [130]. For example, polyacrylamide/gum ghatti/polyaniline
K. Varaprasad et al. / Materials Science and Engineering C 79 (2017) 958971 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 led [143145]. 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 amplier [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 exible
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 lms 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 modications 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 signicant 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 modied 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 rst 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 justiably 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 freezethaw technique. Polysaccharide hydrogels pre-
[140].
pared from freezethaw technique is more biocompatible and biode-
2. CPHs have been proposed as potential conductive exible 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) 958971

linking. These hydrogels are undoubtedly stabilized mainly by the mul- 3.4.1. Raw materials
tiple inter-chain hydrogen bonds in the junction zones of the polymeric Silk broin from spider webs, collagen from skin, keratin as of wool/
network [151]. hair, bone and tendons, elastin as of elastic tissues, brin from blood
By varying the types of polysaccharides, the nature of soluble clots and resilient from insect tendons are the best examples of proteins.
additives and the temperature and duration of freezing, rate of thawing
and the number of refreezing cycles, it is possible to regulate 3.4.2. Preparation methods
and modulate the properties of the nal gels and their macro- and Protein-based hydrogels can be prepared through simple free-radi-
micro-structures. Quite a lot of polysaccharides, such as hyaluronic, cal polymerization method as described by Jayaram et al. [57], where
carboxymethylated-curdlan, carboxymethylated cellulose, xanthan, protein molecules remain in the three-dimensional interpenetrating
b-glucan, locust bean gum, starch (amylose, amylopectin and their hydrogel network.
mixtures), maltodextrins and agarose are capable of forming these An efcient way to obtain protein-based hydrogels, is through graft
gels [151]. However, in the development of a signicant network of polymerization of vinyl monomers onto their backbones in the presence
hydrogels, polysaccharide polymers are more attractive than the of cross-linkers within different initiator systems [159]. The addition of
synthetic polymers, because of their functional properties (good vinyl monomers improves the hydrophilic nature of proteins which ac-
hydrophilicity, biodegradation and biocompatibility). As a result of cordingly improves the water absorption capacity of the resulting pro-
this property, it has been used in biomedical, environmental and tein-based hydrogels. To the best knowledge of the authors [158],
industrial applications. 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.
3.3.3. Applications
Moreover, proteins are characterized by numerous reactive groups,
1. Polysaccharides are widely used in various industries applications
which can be used as sites for chemical modications and cross-link in
like agro-food, paper, cosmetic, textile, biomedical and pharmaceuti-
order to polymeric structures develop [158]. Food protein hydrogels
cal because of their rheological characteristics such as gelling,
are generally obtained using heat treatment, which is problematic for
viscosifying and stabilization of dispersions. On the other hand, due
heat-sensitive active compounds. Hence, cold gelation process is being
to its good tissue compatibility, it has been widely used in the eld
adopted. Recently, soy protein hydrogels, using a cold gelation process
of tissue engineering including regeneration of skin, cartilage, bone
have been proven to be a good option for the delivery of active drugs
and liver, and in the treatment of exuding wounds and in enhancing
[160]. This approach consisted of denaturing a soy protein solution by
the healing process [152,153].
heating, then cooling to room temperature and addition a Maillard
2. Bioactive coatings (e.g. catheter, stent), replacement of nucleus type cross-linker, i.e., glutaraldehyde/glycerol in the absence or pres-
pulpous and cellular scaffold (articial organs) are quite evidently ence of a salt [161].
possible with polysaccharide-based hydrogels.
3. Microporous hydrogels have been extensively used for controlled 3.4.3. Applications
drug release, blood purication, removing the anionic dyes/metal 1. Hydrogels prepared from silk broin have signicant interstitial uid
ions from polluted water [154], regenerative medicine for cell deliv- support and have compressive moduli between 10 kPa and 50 MPa,
ery and wound dressing materials [78,83]. which covers the region of articular cartilage at 0.11.3 MPa. Hence,
4. Acidic cellulosechitin hybrid gel (as novel electrolyte) has been de- they are utilized for articular cartilage repairs [162].
veloped for an electric double layer capacitor. 2. Elastin-like protein hydrogels have been utilized to promote neurite
out-growth and to better appreciate the property of common poly-
3.4. Protein-based hydrogels meric hydrogels design parameters on neuronal cultures. Elastin-
like proteins are produced via yielding engineered protein polymers,
Nature offers an abundance of structural building blocks for hydro- recombinant protein synthesis, that is made entirely of amino acids.
gel fabrication that can be derived from a wide range of natural mate- 3. Elastin-based polymeric hydrogels have shown huge potential for
rials, such as proteins (i.e., silk, collagen, actin and myosin, gelatin, the advanced engineering of elastic tissues, such as skin, lung and
brinogen, elastin, keratin), natural/synthetic polysaccharides (i.e., chi- vasculature. The presence of expandable polymeric bres in blood
tin, cellulose, dextran, amylose and glycosaminoglycan's) or polynucle- vessels enables the vessels to stretch and relax more than a billion
otides (i.e., DNA, RNA) [155]. This wide range of natural materials can times during their life time [163].
form non-cytotoxic polymeric hydrogels [156]. Among these and in par-
ticular, the protein-based polymeric hydrogels can ape features of the 3.5. Hydrogels based on synthetic polymers
extra-cellular system and thus have the potential to promote the migra-
tion, growth for tissue regeneration and wound healing. Protein-based Synthetic polymeric hydrogels constitute a group of materials, used
hydrogels are, therefore, also often suitable materials for cell encapsula- in numerous disciplines and are still in continuous developing stages for
tion [157]. new and promising applications in biomedical and other sciences. Syn-
Of the natural polymers, proteins are the most under-rated as well thetic hydrogels are usually made from poly(hydroxyalkyl methacry-
under-utilized feeds stocks with deference to their advanced industrial lates), Poloxamers, poly(acrylate), poly(acrylic acid), poly(acrylamide)
applications. Proteins have been studied as effective starting materials and poly(methacrylamide) and their derivatives poly(N-vinyl-2-
for the manufacture of several biomaterials, such as lms and compos- pyrolidone) and poly(vinyl alcohol), etc. [82,158]. Synthetic hydrogels
ites [158]. In recent years, brous protein-based hydrogels have become exhibit numerous advantages, such as large water absorption capacities
popular due to their structural and mechanical similarity with the na- and reasonable gel strength and cost. Synthetic hydrogels differ in their
tive extracellular matrix and their relatively simple process-ability characteristics due to their various chemical structures, synthesis tech-
under mild, cell-compatible conditions [157]. niques and water content or cross-linking. It is still possible to design
Hydrogels formed by proteins brous show close up structural, me- new hydrogel that fulls specic functions for specic needs. A change
chanical and chemical similarities with the extracellular matrix, typical- in chemical composition or even a change in one of the synthesis factors
ly superior biological compatibility and can activate precise cellular such as synthesis techniques conditions, cross-linking methods and gels
responses. In addition, these hydrogels can be degraded in the body may lead to new intelligent biomaterials [164].
by proteolytic enzymes. For these reasons, these protein hydrogels are During the last two decades, natural hydrogels have gradually re-
one of the most versatile materials for tissue engineering [157]. placed by synthetic hydrogels that have signicant capacity of water
K. Varaprasad et al. / Materials Science and Engineering C 79 (2017) 958971 967

absorption and long service life and high gel strength. Fortunately, syn- crystalline junction points in the polymer chain and translate into hy-
thetic polymers usually contain well-dened network structures which drogel [170].
can modied to yield tailor-able degradability and functionality. PVA is an interesting synthetic water soluble polymer that can be
Hydrogels can be synthesized from purely synthetic components. In ad- transformed into hydrogels via a variety of mechanisms. PVA can be co-
dition, it is stable in conditions of sharp and strong uctuating temper- valently cross-linked to form a hydrogel. Similarly, PVA gel formation
atures [4]. via hydrogen bonds is also very popular. Its derivative hydrogels can
Some of the synthetic hydrogel systems, e.g. poly(ethylene glycol) be made via repeated freezing and thawing of PVA solution [127]. This
hydrogels are stimuli-sensitive which reacts in the presence of physi- allows the polymer chains to move into sufciently close proximity in
cal/chemical (bio-logical) agent. As a consequence of their unique prop- order to form the hydrogen bonds and subsequent crystalline junction
erties, hydrogels employed for these drug releasing systems are called points. With the increase in a number of freeze-thaw cycles, tougher hy-
smart or intelligent gels. Physical stimuli include solvent, light, tem- drogel could be produced.
perature, radiation (UV), pressure, magnetic, acoustic/electrical eld,
while the chemical and biological stimuli consist of pH, molecular rec- 3.5.3. Applications
ognition events and precise ions [164]. It is a known fact that wound 1. Poly(hydroxyethyl methacrylate) ensures good wound-healing con-
care materials that provide the skin with a moist environment, favour ditions and therefore, it is most widely applied in dressings, especial-
epithelial cells and tissue reconstruction and therefore, change of dress- ly burn dressings applications. It is used in contact lenses, drug
ing is less harmful. This role is excellently played by poly(vinyl alcohol) delivery and tissue engineering purposes for marrow and spinal
(PVA)-based hydrogels, which possess the ability to retain water in the cord cell regeneration and as scaffolds for promoting cell adhesion
structure and ensure a prolonged moist environment [164]. These and in articial skin manufacturing, articial cartilage production ap-
hydrogels are also soft, transparent and have good permeabilitysince plications [164].
oxygen passes through them relatively easily. Furthermore, non-modi- 2. PVA vitreous has been employed in a variety of biomedical applica-
ed PVA does not adhere well to cells or proteins, which makes it attrac- tions, including drug delivery, articial tears, contact lenses, articial
tive for new tissue engineering purposes [165,166]. Poloxamers are cell encapsulation and more recently, as nerve cuffs [170]. PVA hy-
amphiphilic non-ionic synthetic [poly(ethylene oxide)-poly(propylene drogel applications encompass injectable implants, endo-prostheses
oxide)] block polymers of hydrophobic propylene oxide and hydrophil- or soft tissue llers in plastic, cartilage reconstructive, aesthetic sur-
ic ethylene oxide comprising a central poly(oxypropylene) molecule, gery, articial organs, drugs systems and wound dressings, providing
which is anked on both said by two chains poly(oxyethylene) [167]. the humid environment that is benecial for wound healing [171].
Poloxamers have similar chemical structure, except they have a change- 3. Poly(ethylene glycol), PEG-based hydrogels are characterized for
able number of poly(oxypropylene) and poly(oxyethylene) units, and their high biocompatibility, lack of toxic inuence on the surround-
consequently, they differ in their molecular weight (Poloxamer 188, ing tissue and solubility in water, which make them good candidates
and 407) [167]. Due to its hydrophobic and hydrophilic nature, they for drug delivery applications [164]. They are used as matrices for cell
are used in pharmaceutical formulations as surfactants, emulsifying delivery for promoting tissue regeneration.
agents, solubilizing agent, dispersing agents, in vivo absorbance en- 4. Thermosensitive tri-block poly(ethylene-glycol)-poly(-
hancer and wound care applications [168,169]. caprolactone)-poly(ethylene glycol) hydrogels formed in-situ, can
be easily applied in several biomedical applications such as cell en-
3.5.1. Raw materials capsulation, controlled drug delivery and tissue repair. Poly(imide)
Raw materials include poly(N-vinyl-pyrrolidone), anionic and cat- (PI) hydrogels and PVA hydrogels has been used in plastic and recon-
ionic hydrogels, poly(electrolyte complexes) and poly(vinyl alcohol). structive surgery [164].
In addition, Poly(hydroxyalkyl methacrylates), poly(acrylate), poly(- 5. Polyacrylate (PA) based polymeric hydrogels play a signicant role in
acrylamide) and poly(meth-acrylamide) and its derivatives poly(N- advanced biomedical applications in aesthetic corrections, as soft tissue
vinyl-2-pyrolidone) and poly(vinyl alcohol) are also used. llers and augmentation materials. Besides silicone, PAA tops the list of
applications in breast augmentation in Eastern Europe and Asia [164].
3.5.2. Preparation methods 6. Poly(urethane) hydrogels are applied as drug carriers, in wound
Synthetic hydrogels may be synthesized in a number of ways. The dressing materials manufacture, articial kidney membranes, cathe-
polymer engineers can design and synthesize synthetic hydrogels ter coating materials and contact lenses [172,173]. Furthermore,
with modied characteristic such as mechanical strength, bio-degrada- hydrogels made of poly(urethane)/poly(acrylamide) are used for
tion, chemical and biological responses to stimuli, either by chemical or dressings, articial muscles, sensor systems and bio-separators.
physical cross-linking methods [4].
Chemically cross-linked hydrogels are three dimensional polymer 4. Conclusion and future prospective
networks that have bonds between the chains. Many hydrogels are
products made of covalent bonds (Section 2). These hydrogels can Without a doubt, there are a number of signicant features of poly-
also be formed directly from hydrophobic monomers. Monomers, meric hydrogels that qualies and allows them to exhibit extraordinary
such as vinyl pyrrolidone, methacrylic acid and poly-2-hydroxyethyl characteristics, which enables them to be employed as essentials tools
methacrylate form the basis of hydrogel formation and they are mostly for applications in almost all the elds, such as biomedical, agricultural,
used in the fabrication of contact lenses. Additionally, hydrogel can also industrial and environmental areas. From time-to-time, signicant
be engineered via the cross-linking of hydrophilic polymer chains. modications are made to revolutionize the eld of hydrogels for their
Among the methods of cross-linking, the utilization of hydrolysis/radia- comprehensive applications. In this review, polymeric hydrogels, corre-
tion of hydrophobic polymeric network is very popular [170]. sponding to the recent generations of the materials, have been exten-
Hydrogels formed from physical interaction are broad class of 3D sively researched and their technical utilizations have been succinctly
biomaterials. These interactions can be formed by crystalline junctions, discussed. Recent developments (in diverse classications) of
hydrogen bonding, phase-separation or other associations. The strength hydrogels, have revolutionized the present research, in relation to
of the hydrogel depends on the strength of these physical bonds and drug delivery systems, electrical conducting, purication of water, agri-
their density. Hydrogen bond formation results from the interaction be- cultural sector, decontamination of organic waste, etc., and these devel-
tween a hydrogen atom and an electronegative atom, e.g., oxygen. Al- opments are presented in this comprehensive review of the different
though the bond is relatively weak when compared to a covalent types of hydrogels such as superabsorbent hybrid hydrogels,
bond, it can still be structurally stable. These hydrogen bonds create Conducting polymer hydrogels, Polysaccharide-based natural
968 K. Varaprasad et al. / Materials Science and Engineering C 79 (2017) 958971

hydrogels, Protein-based hydrogels, Hydrogels based on synthetic poly- [16] Y. Liu, N.E. Vrana, P.A. Cahill, G.B. McGuinness, Physically crosslinked composite
hydrogels of PVA with natural macromolecules: structure, mechanical properties,
mers, Bio-polymer based hydrogel for the decontamination of organic and endothelial cell compatibility, J. Biomed. Mater. Res. B Appl. Biomater. 90B
waste and other hydrogels, their preparations and applications are suc- (2009) 492502, http://dx.doi.org/10.1002/jbm.b.31310.
cinctly discussed. [17] W.E. Hennink, S.J. De Jong, G.W. Bos, T.F.J. Veldhuis, C.F. van Nostrum, Biodegrad-
able dextran hydrogels crosslinked by stereocomplex formation for the controlled
For future studies, more attention should be focused in order to meet release of pharmaceutical proteins, Int. J. Pharm. 277 (2004) 99104, http://dx.doi.
the specic requirements of advanced and sophisticated drug delivery org/10.1016/j.ijpharm.2003.02.002.
systems. Cross-linked architectures of monomers, pre-polymers and [18] S.J. de Jong, S.C. De Smedt, J. Demeester, C.F. van Nostrum, J.J. Kettenes-van den
Bosch, W.E. Hennink, Biodegradable hydrogels based on stereocomplex formation
polymers, would remain as the most preferred delivery device. between lactic acid oligomers grafted to dextran, J. Control. Release 72 (2001)
Green, describes the use of (safe solvents, no solvent at all or nontoxic 4756, http://dx.doi.org/10.1016/S0168-3659(01)00261-9.
cross-linkers) and/or low-energy processing for hydrogel systems. In- [19] R. Wang, S.K. Both, M. Geven, L. Calucci, C. Forte, P.J. Dijkstra, M. Karperien, Kinet-
ically stable metal ligand charge transfer complexes as crosslinks in nanogels/
jectable hydrogels that can be safely formed within the body without
hydrogels: physical properties and cytotoxicity, Acta Biomater. 26 (2015)
the need of surgery, for targeting drug release or tissue engineering de- 136144, http://dx.doi.org/10.1016/j.actbio.2015.08.019.
velopment of hydrogel functionalization, will undoubtedly, be a wel- [20] N. Masruchin, B.-D. Park, V. Causin, Inuence of sonication treatment on supramo-
coming convenience for the end users. Realizing the usage lecular cellulose microbril-based hydrogels induced by ionic interaction, J. Ind.
Eng. Chem. 29 (2015) 265272, http://dx.doi.org/10.1016/j.jiec.2015.03.034.
requirements, while limiting the complexity of the hydrogel formula- [21] Y. Ishii-Mizuno, Y. Umeki, Y. Onuki, H. Watanabe, Y. Takahashi, Y. Takakura, M.
tion, will be the main goal for the coming decades. Although, extensive Nishikawa, Improved sustained release of antigen from immunostimulatory DNA
research is on-going in order to provide new kind of hydrogels for future hydrogel by electrostatic interaction with chitosan, Int. J. Pharm. 516 (2017)
392400, http://dx.doi.org/10.1016/j.ijpharm.2016.11.048.
necessities, novel conceptual assimilation of hydrogel preparation may [22] X. Ye, X. Li, Y. Shen, G. Chang, J. Yang, Z. Gu, Self-healing pH-sensitive cytosine- and
lead to tailored properties, translating its innovative applications in guanosine-modied hyaluronic acid hydrogels via hydrogen bonding, Polymer
the diversied elds. Above all, an economical way to improve the ef- (Guildf) 108 (2017) 348360, http://dx.doi.org/10.1016/j.polymer.2016.11.063.
[23] W. Feng, W. Zhou, Z. Dai, A. Yasin, H. Yang, Tough polypseudorotaxane supramo-
cacy of the hydrogel system will be the most demandingly needed lecular hydrogels with dual-responsive shape memory properties, J. Mater.
approach. Chem. B 4 (2016) 19241931, http://dx.doi.org/10.1039/C5TB02737C.
[24] Y. Yu, K.K. Moncal, J. Li, W. Peng, I. Rivero, J.A. Martin, I.T. Ozbolat, Three-dimen-
sional bioprinting using self-assembling scalable scaffold-free tissue strands as
Acknowledgements a new bioink, Sci. Rep. 6 (2016) 28714, http://dx.doi.org/10.1038/srep28714.
[25] I.E. Erickson, S.R. Kestle, K.H. Zellars, G.R. Dodge, J.A. Burdick, R.L. Mauck, Improved
cartilage repair via in vitro pre-maturation of MSC seeded hyaluronic acid
The author, Kokkarachedu Varaprasad wishes to acknowledge the hydrogels, Biomed. Mater. 7 (2012) 24110, http://dx.doi.org/10.1088/1748-6041/
Fondecyt Proyecto No 11160073, Programa de Atraccin e Insercin 7/2/024110.
de Capital Humano Avanzado (PAI) Proyecto No 78130211 Conicyt, [26] A. Abaee, A. Madadlou, A.A. Saboury, The formation of non-heat-treated whey pro-
tein cold-set hydrogels via non-toxic chemical cross-linking, Food Hydrocoll. 63
Chile, and the Centro de Investigacin de Polmeros Avanzados (CIPA),
(2017) 4349, http://dx.doi.org/10.1016/j.foodhyd.2016.08.024.
CONICYT Regional, GORE BIO-BIO PRFC0002. The author MMY acknowl- [27] B.-H. Hu, J. Su, P.B. Messersmith, Hydrogels cross-linked by native chemical liga-
edge National Institute of Health/National Cancer Center's Career Devel- tion, Biomacromolecules 10 (2009) 21942200, http://dx.doi.org/10.1021/
opment Award K22 CA174841. bm900366e.
[28] H.A. Essawy, M.B.M. Ghazy, F.A. El-Hai, M.F. Mohamed, Superabsorbent hydrogels
via graft polymerization of acrylic acid from chitosan-cellulose hybrid and their po-
References tential in controlled release of soil nutrients, Int. J. Biol. Macromol. 89 (2016)
144151, http://dx.doi.org/10.1016/j.ijbiomac.2016.04.071.
[1] O. Wichterle, D. Lim, Hydrophilic Gels for Biological Use, 1960. [29] Y.-M. An, T. Liu, R. Tian, S.-X. Liu, Y.-N. Han, Q.-Q. Wang, W.-J. Sheng, Synthesis of
[2] W.E. Roorda, H.E. Bodde, A.G. De Boer, H.E. Junginger, Synthetic hydrogels as drug novel temperature responsive PEG-b-[PCL-g-P(MEO2MA-co-OEGMA)]-b-PEG
delivery systems, Pharm. Weekbl. 8 (1986) 165189, http://dx.doi.org/10.1007/ (tBG) triblock-graft copolymers and preparation of tBG/graphene oxide composite
BF01959775. hydrogels via click chemistry, React. Funct. Polym. 94 (2015) 18, http://dx.doi.
[3] S.J. Buwalda, K.W.M. Boere, P.J. Dijkstra, J. Feijen, T. Vermonden, W.E. Hennink, org/10.1016/j.reactfunctpolym.2015.05.011.
Hydrogels in a historical perspective: from simple networks to smart materials, J. [30] T.H. Tran, H. Okabe, Y. Hidaka, K. Hara, Removal of metal ions from aqueous solu-
Control. Release 190 (2014) 254273. tions using carboxymethyl cellulose/sodium styrene sulfonate gels prepared by ra-
[4] E.M. Ahmed, Hydrogel: preparation, characterization, and applications: a review, J. diation grafting, Carbohydr. Polym. 157 (2017) 335343, http://dx.doi.org/10.
Adv. Res. 6 (2015) 105121. 1016/j.carbpol.2016.09.049.
[5] M.J. Zohuriaan-Mehr, K. Kabiri, Superabsorbent polymer materials: a review, Iran. [31] A. Cruz, L. Garca-Uriostegui, A. Ortega, T. Isoshima, G. Burillo, Radiation grafting of
Polym. J. 17 (2008) 451. N-vinylcaprolactam onto nano and macrogels of chitosan: synthesis and character-
[6] S.K.H. Gulrez, G.O. Phillips, S. Al-Assaf, Hydrogels: Methods of Preparation, Charac- ization, Carbohydr. Polym. 155 (2017) 303312, http://dx.doi.org/10.1016/j.
terisation and Applications, INTECH Open Access Publisher, 2011. carbpol.2016.08.083.
[7] N.A. Peppas, P. Bures, W. Leobandung, H. Ichikawa, Hydrogels in pharmaceutical [32] K. Varaprasad, R. Sadiku, Development of microbial protective Kolliphor-based
formulations, Eur. J. Pharm. Biopharm. 50 (2000) 2746, http://dx.doi.org/10. nanocomposite hydrogels, J. Appl. Polym. Sci. 132 (2015) n/a, http://dx.doi.org/
1016/S0939-6411(00)00090-4. 10.1002/app.42781.
[8] J.A. Rowley, G. Madlambayan, D.J. Mooney, Alginate hydrogels as synthetic extra- [33] J. Wang, J. Wei, Hydrogel brushes grafted from stainless steel via surface-initiated
cellular matrix materials, Biomaterials 20 (1999) 4553. atom transfer radical polymerization for marine antifouling, Appl. Surf. Sci. 382
[9] W.A. Laftah, S. Hashim, A.N. Ibrahim, Polymer hydrogels: a review, Polym.-Plast. (2016) 202216, http://dx.doi.org/10.1016/j.apsusc.2016.03.223.
Technol. Eng. 50 (2011) 14751486. [34] H. Zhao, J. Gao, R. Liu, S. Zhao, Stimulus-responsiveness and methyl violet release
[10] G.M. Raghavendra, K. Varaprasad, T. Jayaramudu, in: Y. Grohens, N.B.T.-N.A. for T.E behaviors of poly(NIPAAm-co-AA) hydrogels chemically crosslinked with??-cyclo-
Ninan (Eds.), Chapter 2 - Biomaterials: Design, Development and Biomedical Ap- dextrin polymer bearing methacrylates, Carbohydr. Res. 428 (2016) 7986, http://
plications A2 - Thomas, Sabu, William Andrew Publishing, Oxford 2015, dx.doi.org/10.1016/j.carres.2016.04.018.
pp. 2144, http://dx.doi.org/10.1016/B978-0-323-32889-0.00002-9. [35] R. Kobe, K. Yoshitani, Y. Teramoto, Fabrication of elastic composite hydrogels using
[11] K. Varaprasad, K. Vimala, G.M. Raghavendra, T. Jayaramudu, E.R. Sadiku, K. Ramam, surface-modied cellulose nanober as a multifunctional crosslinker, J. Appl.
in: Y. Grohens, N.B.T.-N.A. for T.E Ninan (Eds.), Chapter 10 - Cell Encapsulation in Polym. Sci. 133 (2016) n/a, http://dx.doi.org/10.1002/app.42906.
Polymeric Self-assembled Hydrogels A2 - Thomas, Sabu, William Andrew Publish- [36] Q. Wei, M. Xu, C. Liao, Q. Wu, M. Liu, Y. Zhang, C. Wu, L. Cheng, Q. Wang, Printable
ing, Oxford 2015, pp. 149171, http://dx.doi.org/10.1016/B978-0-323-32889-0. hybrid hydrogel by dual enzymatic polymerization with superactivity, Chem. Sci. 7
00010-8. (2016) 27482752, http://dx.doi.org/10.1039/C5SC02234G.
[12] K. Sharma, B.S. Kaith, V. Kumar, S. Kalia, V. Kumar, H.C. Swart, Water retention and [37] M.-M. Sadat Ebrahimi, Y. Voss, H. Schnherr, Rapid detection of Escherichia coli via
dye adsorption behavior of Gg-cl-poly (acrylic acid-aniline) based conductive enzymatically triggered reactions in self-reporting chitosan hydrogels, ACS Appl.
hydrogels, Geoderma 232 (2014) 4555. Mater. Interfaces 7 (2015) 2019020199, http://dx.doi.org/10.1021/acsami.
[13] B.V. Slaughter, S.S. Khurshid, O.Z. Fisher, A. Khademhosseini, N.A. Peppas, 5b05746.
Hydrogels in regenerative medicine, Adv. Mater. 21 (2009) 33073329. [38] Z.R. Miladinovic, M. Micic, E. Suljovrujic, Temperature/pH dual responsive OPGMA
[14] H.J. Chung, T.G. Park, Self-assembled and nanostructured hydrogels for drug deliv- based copolymeric hydrogels prepared by gamma radiation: an optimisation
ery and tissue engineering, Nano Today 4 (2009) 429437. study, J. Polym. Res. 23 (2016) 77, http://dx.doi.org/10.1007/s10965-016-0975-8.
[15] J. Schulze, S. Hendrikx, M. Schulz-Siegmund, A. Aigner, Microparticulate poly(vinyl [39] A.S. Chaykar, F. Goharpey, J.K. Yeganeh, Volume phase transition of electron beam
alcohol) hydrogel formulations for embedding and controlled release of cross-linked thermo-responsive PVME nanogels in the presence and absence of
polyethylenimine (PEI)-based nanoparticles, Acta Biomater. 45 (2016) 210222, nanoparticles: with a view toward rheology and interactions, RSC Adv. 6 (2016)
http://dx.doi.org/10.1016/j.actbio.2016.08.056. 96939708, http://dx.doi.org/10.1039/C5RA21021F.
K. Varaprasad et al. / Materials Science and Engineering C 79 (2017) 958971 969

[40] C.M. Hassan, N.A. Peppas, Structure and applications of poly (vinyl alcohol) [67] R. Dong, Y. Pang, Y. Su, X. Zhu, Supramolecular hydrogels: synthesis, properties and
hydrogels produced by conventional crosslinking or by freezing/thawing methods, their biomedical applications, Biomater. Sci. 3 (2015) 937954.
Biopolym. PVA Hydrogels, Anionic Polym. Nanocomposites, Springer 2000, [68] O.Z. Fisher, A. Khademhosseini, R. Langer, N.A. Peppas, Bioinspired materials for
pp. 3765. controlling stem cell fate, Acc. Chem. Res. 43 (2009) 419428.
[41] F.M. Plieva, M. Karlsson, M.R. Aguilar, D. Gomez, S. Mikhalovsky, I.Y. Galaev, B. [69] A.M. Lowman, Peppas, Hydrogels, Encyclopedia of Controlled Drug Delivery, Vol. 1,
Mattiasson, Pore structure of macroporous monolithic cryogels prepared from 1999. http://dx.doi.org/10.1038/185117a0.
poly(vinyl alcohol), J. Appl. Polym. Sci. 100 (2006) 10571066, http://dx.doi.org/ [70] A.K. Gaharwar, N.A. Peppas, A. Khademhosseini, Nanocomposite hydrogels for bio-
10.1002/app.23200. medical applications, Biotechnol. Bioeng. 111 (2014) 441453.
[42] T. Jayaramudu, Y. Li, H.-U. Ko, I.R. Shishir, J. Kim, Poly(acrylic acid)-poly(vinyl alco- [71] J. Shen, B. Yan, T. Li, Y. Long, N. Li, M. Ye, Mechanical, thermal and swelling proper-
hol) hydrogels for recongurable lens actuators, Int. J. Precis. Eng. Manuf. Technol. ties of poly (acrylic acid)graphene oxide composite hydrogels, Soft Matter 8
3 (2016) 375379, http://dx.doi.org/10.1007/s40684-016-0047-x. (2012) 18311836.
[43] V.I. Lozinsky, F.M. Plieva, Poly(vinyl alcohol) cryogels employed as matrices for cell [72] S.R. Shin, H. Bae, J.M. Cha, J.Y. Mun, Y.-C. Chen, H. Tekin, H. Shin, S. Farshchi, M.R.
immobilization. 3. Overview of recent research and developments, Enzym. Microb. Dokmeci, S. Tang, Carbon nanotube reinforced hybrid microgels as scaffold mate-
Technol. 23 (1998) 227242, http://dx.doi.org/10.1016/S0141-0229(98)00036-2. rials for cell encapsulation, ACS Nano 6 (2011) 362372.
[44] H. Tsuji, F. Horii, M. Nakagawa, Y. Ikada, H. Odani, R. Kitamaru, Stereocomplex for- [73] K. Varaprasad, G. Siva Mohan Reddy, J. Jayaramudu, R. Sadiku, K. Ramam, S.S.S. Ray,
mation between enantiomeric poly(lactic acid)s. 7. Phase structure of the Development of microbial resistant Carbopol nanocomposite hydrogels via a green
stereocomplex crystallized from a dilute acetonitrile solution as studied by high- process, Biomater. Sci. 2 (2014) 257263, http://dx.doi.org/10.1039/C3BM60185D.
resolution solid-state carbon-13 NMR spectroscopy, Macromolecules 25 (1992) [74] K. Varaprasad, K. Vimala, S. Ravindra, N.N. Reddy, K.M. Raju, Development of sodi-
41144118, http://dx.doi.org/10.1021/ma00042a011. um carboxymethyl cellulose-based poly(acrylamide-co-2acrylamido-2-methyl-1-
[45] H. Tsuji, Poly (lactide) stereocomplexes: formation, structure, properties, degrada- propane sulfonic acid) hydrogels for in vitro drug release studies of ranitidine hy-
tion, and applications, Macromol. Biosci. 5 (2005) 569597. drochloride an anti-ulcer drug, Polym.-Plast. Technol. Eng. 50 (2011) 11991207,
[46] Q.S. Zhao, Q.X. Ji, K. Xing, X.Y. Li, C.S. Liu, X.G. Chen, Preparation and characteristics of http://dx.doi.org/10.1080/03602559.2011.553872.
novel porous hydrogel lms based on chitosan and glycerophosphate, Carbohydr. [75] Kokkarachedu Varaprasad, K. Vimala, Sakey Ravindra, N. Narayana Reddy, G. Siva
Polym. 76 (2009) 410416, http://dx.doi.org/10.1016/j.carbpol.2008.11.020. Mohana Reddy, K. Mohana Raju, Biodegradable chitosan hydrogels for in vitro
[47] M. Ebara, Y. Kotsuchibashi, R. Narain, N. Idota, Y.-J. Kim, J.M. Hoffman, K. Uto, T. drug release studies of 5-urouracil an anticancer drug, J. Polym. Environ. 20
Aoyagi, Smart Biomaterials, Springer, 2014. (2012) 573582, http://dx.doi.org/10.1007/s10924-012-0412-y.
[48] M. Takigami, H. Amada, N. Nagasawa, T. Yagi, T. Kasahara, S. Takigami, M. Tamada, [76] K. Varaprasad, N.N. Reddy, N.M. Kumar, K. Vimala, S. Ravindra, K.M. Raju, Poly (ac-
Preparation and properties of CMC gel, Trans. Res. Soc. JAPAN 32 (2007) 713. rylamide-chitosan) hydrogels: interaction with surfactants, Int. J. Polym. Mater. 59
[49] H. Aoki, S. Al-Assaf, T. Katayama, G.O. Phillips, Characterization and properties of (2010) 981993.
Acacia senegal (L.) Willd. var. senegal with enhanced properties (Acacia (sen) [77] M. Yadollahi, I. Gholamali, H. Namazi, M. Aghazadeh, Synthesis and characteriza-
SUPER GUM): part 2mechanism of the maturation process, Food Hydrocoll. tion of antibacterial carboxymethylcellulose/CuO bio-nanocomposite hydrogels,
21 (2007) 329337, http://dx.doi.org/10.1016/j.foodhyd.2006.04.002. Int. J. Biol. Macromol. 73 (2015) 109114, http://dx.doi.org/10.1016/j.ijbiomac.
[50] H. Aoki, T. Katayama, T. Ogasawara, Y. Sasaki, S. Al-Assaf, G.O. Phillips, Characteri- 2014.10.063.
zation and properties of Acacia senegal (L.) Willd. var. Senegal with enhanced prop- [78] T. Jayaramudu, G.M. Raghavendra, K. Varaprasad, R. Sadiku, K. Ramam, K.M. Raju,
erties (Acacia (sen) SUPER GUM): part 5. Factors affecting the emulsication of Iota-carrageenan-based biodegradable Ag0 nanocomposite hydrogels for the inac-
Acacia senegal and Acacia (sen) SUPER GUM, Food Hydrocoll. 21 (2007) tivation of bacteria, Carbohydr. Polym. 95 (2013) 188194, http://dx.doi.org/10.
353358, http://dx.doi.org/10.1016/j.foodhyd.2006.04.014. 1016/j.carbpol.2013.02.075.
[51] W.E. Hennink, C.F. van Nostrum, Novel crosslinking methods to design hydrogels, [79] G.M. Raghavendra, J. Jung, J. Seo, Step-reduced synthesis of starch-silver nanopar-
Adv. Drug Deliv. Rev. 54 (2002) 1336, http://dx.doi.org/10.1016/S0169- ticles, Int. J. Biol. Macromol. 86 (2016) 126128.
409X(01)00240-X. [80] G.M. Raghavendra, J. Jung, D. Kim, J. Seo, Microwave assisted antibacterial chito-
[52] I.C. Alupei, M. Popa, M. Hamcerencu, M.J.M. Abadie, Superabsorbant hydrogels sansilver nanocomposite lms, Int. J. Biol. Macromol. 84 (2016) 281288,
based on xanthan and poly (vinyl alcohol): 1. The study of the swelling properties, http://dx.doi.org/10.1016/j.ijbiomac.2015.12.026.
Eur. Polym. J. 38 (2002) 23132320. [81] T. Jayaramudu, G.M. Raghavendra, K. Varaprasad, G.V.S. Reddy, A.B. Reddy, K.
[53] V.D. Athawale, V. Lele, Graft copolymerization onto starch. II. Grafting of acrylic Sudhakar, E.R. Sadiku, Preparation and characterization of poly(ethylene glycol)
acid and preparation of it's hydrogels, Carbohydr. Polym. 35 (1998) 2127, stabilized nano silver particles by a mechanochemical assisted ball mill process,
http://dx.doi.org/10.1016/S0144-8617(97)00138-0. J. Appl. Polym. Sci. 133 (2016) n/a, http://dx.doi.org/10.1002/app.43027.
[54] H.M. Said, S.G.A. Alla, A.W.M. El-Naggar, Synthesis and characterization of novel [82] G.M. Raghavendra, T. Jayaramudu, K. Varaprasad, G.S. Mohan Reddy, K.M. Raju, An-
gels based on carboxymethyl cellulose/acrylic acid prepared by electron beam irra- tibacterial nanocomposite hydrogels for superior biomedical applications: a facile
diation, React. Funct. Polym. 61 (2004) 397404. eco-friendly approach, RSC Adv. 5 (2015) 1435114358, http://dx.doi.org/10.
[55] K. Varaprasad, Y.M. Mohan, S. Ravindra, N.N. Reddy, K. Vimala, K. Monika, B. 1039/C4RA15995K.
Sreedhar, K.M. Raju, Hydrogelsilver nanoparticle composites: a new generation [83] Y. Murali Mohan, K. Vimala, V. Thomas, K. Varaprasad, B. Sreedhar, S.K. Bajpai, K.
of antimicrobials, J. Appl. Polym. Sci. 115 (2010) 11991207. Mohana Raju, Controlling of silver nanoparticles structure by hydrogel networks, J.
[56] T. Jayaramudu, G.M. Raghavendra, K. Varaprasad, K.M. Raju, E.R. Sadiku, J. Kim, 5- Colloid Interface Sci. 342 (2010) 7382, http://dx.doi.org/10.1016/j.jcis.2009.10.008.
Fluorouracil encapsulated magnetic nanohydrogels for drug-delivery applications, [84] P.S.K. Murthy, Y. Murali Mohan, K. Varaprasad, B. Sreedhar, K. Mohana Raju, First
J. Appl. Polym. Sci. 133 (2016) 110, http://dx.doi.org/10.1002/app.43921. successful design of semi-IPN hydrogelsilver nanocomposites: a facile approach
[57] T. Jayaramudu, G.M. Raghavendra, K. Varaprasad, R. Sadiku, K.M. Raju, Develop- for antibacterial application, J. Colloid Interface Sci. 318 (2008) 217224, http://
ment of novel biodegradable Au nanocomposite hydrogels based on wheat: for in- dx.doi.org/10.1016/j.jcis.2007.10.014.
activation of bacteria, Carbohydr. Polym. 92 (2013) 21932200, http://dx.doi.org/ [85] G.M. Raghavendra, T. Jayaramudu, K. Varaprasad, S. Ramesh, K.M. Raju, Microbial
10.1016/j.carbpol.2012.12.006. resistant nanocurcumin-gelatin-cellulose bers for advanced medical applications,
[58] A.E.J. de Nooy, D. Capitani, G. Masci, V. Crescenzi, Ionic polysaccharide hydrogels RSC Adv. 4 (2014) 34943501, http://dx.doi.org/10.1039/C3RA46429F.
via the Passerini and Ugi multicomponent condensations: synthesis, behavior [86] K. Varaprasad, G.M. Raghavendra, T. Jayaramudu, J. Seo, Nano zinc oxidesodium
and solid-state NMR characterization, Biomacromolecules 1 (2000) 259267, alginate antibacterial cellulose bres, Carbohydr. Polym. 135 (2016) 349355,
http://dx.doi.org/10.1021/bm005517h. http://dx.doi.org/10.1016/j.carbpol.2015.08.078.
[59] A.E.J. de Nooy, G. Masci, V. Crescenzi, Versatile synthesis of polysaccharide [87] G.M. Raghavendra, T. Jayaramudu, K. Varaprasad, R. Sadiku, S.S.S. Ray, K. Mohana
hydrogels using the Passerini and Ugi multicomponent condensations, Macromol- Raju, CellulosepolymerAg nanocomposite bers for antibacterial fabrics/skin
ecules 32 (1999) 13181320, http://dx.doi.org/10.1021/ma9815455. scaffolds, Carbohydr. Polym. 93 (2013) 553560, http://dx.doi.org/10.1016/j.
[60] J.J. Sperinde, L.G. Grifth, Synthesis and characterization of enzymatically-cross- carbpol.2012.12.035.
linked poly(ethylene glycol) hydrogels, Macromolecules 30 (1997) 52555264, [88] N. Yuan, L. Xu, L. Zhang, H. Ye, J. Zhao, Z. Liu, J. Rong, Superior hybrid hydrogels of
http://dx.doi.org/10.1021/ma970345a. polyacrylamide enhanced by bacterial cellulose nanober clusters, Mater. Sci. Eng.
[61] L. Zhao, H. Mitomo, M. Zhai, F. Yoshii, N. Nagasawa, T. Kume, Synthesis of antibac- C 67 (2016) 221230.
terial PVA/CM-chitosan blend hydrogels with electron beam irradiation, [89] Z. Barabadi, M. Azami, E. Shari, R. Karimi, N. Lotbakhshaiesh, R. Roozafzoon, M.T.
Carbohydr. Polym. 53 (2003) 439446, http://dx.doi.org/10.1016/S0144- Joghataei, J. Ai, Fabrication of hydrogel based nanocomposite scaffold containing
8617(03)00103-6. bioactive glass nanoparticles for myocardial tissue engineering, Mater. Sci. Eng. C
[62] M. Zhai, F. Yoshii, T. Kume, K. Hashim, Syntheses of PVA/starch grafted hydrogels 69 (2016) 11371146, http://dx.doi.org/10.1016/j.msec.2016.08.012.
by irradiation, Carbohydr. Polym. 50 (2002) 295303, http://dx.doi.org/10.1016/ [90] Y. Hu, G. Ren, L. Deng, J. Zhang, H. Liu, S. Mu, T. Wu, Degradable UV-crosslinked hy-
S0144-8617(02)00031-0. drogel for the controlled release of triclosan with reduced cytotoxicity, Mater. Sci.
[63] R. Kishi, H. Ichijo, O. Hirasa, Thermo-responsive devices using poly (vinyl methyl Eng. C 67 (2016) 151158, http://dx.doi.org/10.1016/j.msec.2016.05.003.
ether) hydrogels, J. Intell. Mater. Syst. Struct. 4 (1993) 533537. [91] A. Palantoken, M. Sari Yilmaz, M. Altikatolu Yapaz, E. Yenigl Tulunay, T. Eren, S.
[64] M. Suzuki, O. Hirasa, An approach to articial muscle using polymer gels formed by Piskin, Dual antimicrobial effects induced by hydrogel incorporated with UV-cur-
micro-phase separation, Responsive Gels Vol. Transitions II, Springer 1993, able quaternary ammonium polyethyleneimine and AgNO3, Mater. Sci. Eng. C 68
pp. 241261. (2016) 494504, http://dx.doi.org/10.1016/j.msec.2016.06.005.
[65] S. Chaterji, I.K. Kwon, K. Park, Smart polymeric gels: redening the limits of bio- [92] E.I. Nep, B.R. Conway, Grewia gum 2: mucoadhesive properties of compacts and
medical devices, Prog. Polym. Sci. 32 (2007) 10831122. gels, Trop. J. Pharm. Res. 10 (2011) 393401.
[66] E. Ye, P.L. Chee, A. Prasad, X. Fang, C. Owh, V.J.J. Yeo, X.J. Loh, Supramolecular soft [93] E. Bilensoy, Y. rpanl, M. en, A.L. Doan, S. al, Thermosensitive mucoadhesive
biomaterials for biomedical applications, In-Situ Gelling Polym, Springer 2015, gel formulation loaded with 5-Fu: cyclodextrin complex for HPV-induced cervical
pp. 107125. cancer, J. Incl. Phenom. Macrocycl. Chem. 57 (2007) 363370.
970 K. Varaprasad et al. / Materials Science and Engineering C 79 (2017) 958971

[94] P. Tangri, N.S. Madhav, Oral mucoadhesive drug delivery systems: a review, JBI [121] S. Peng, J.Y. Lin, M.H. Cheng, C.W. Wu, I.M. Chu, A cell-compatible PEOPPOPEO
2229 (2011) 7499. (Pluronic)-based hydrogel stabilized through secondary structures, Mater. Sci.
[95] C. Tang, A.F. Miller, A. Saiani, Peptide hydrogels as mucoadhesives for local drug de- Eng. C 69 (2016) 421428, http://dx.doi.org/10.1016/j.msec.2016.06.091.
livery, Int. J. Pharm. 465 (2014) 427435. [122] M. Jain, K. Matsumura, Thixotropic injectable hydrogel using a polyampholyte and
[96] J. Xu, S. Strandman, J.X.X. Zhu, J. Barralet, M. Cerruti, Genipin-crosslinked catechol- nanosilicate prepared directly after cryopreservation, Mater. Sci. Eng. C 69 (2016)
chitosan mucoadhesive hydrogels for buccal drug delivery, Biomaterials 37 (2015) 12731281, http://dx.doi.org/10.1016/j.msec.2016.08.030.
395404. [123] L. Zhao, X. Li, J. Zhao, S. Ma, X. Ma, D. Fan, C. Zhu, Y. Liu, A novel smart injectable
[97] B. Singh, L. Varshney, V. Sharma, Design of sterile mucoadhesive hydrogels for use hydrogel prepared by microbial transglutaminase and human-like collagen: its
in drug delivery: effect of radiation on network structure, Colloids Surf. B: characterization and biocompatibility, Mater. Sci. Eng. C 68 (2016) 317326,
Biointerfaces 121 (2014) 230237. http://dx.doi.org/10.1016/j.msec.2016.05.108.
[98] X. Xu, Y. Shen, W. Wang, C. Sun, C. Li, Y. Xiong, J. Tu, Preparation and in vitro [124] P. Kakkar, B. Madhan, Fabrication of keratin-silica hydrogel for biomedical applica-
characterization of thermosensitive and mucoadhesive hydrogels for nasal tions, Mater. Sci. Eng. C 66 (2016) 178184, http://dx.doi.org/10.1016/j.msec.2016.
delivery of phenylephrine hydrochloride, Eur. J. Pharm. Biopharm. 88 (2014) 04.067.
9981004. [125] A.C.S. Akkari, J.Z.B. Papini, G.K. Garcia, M.K.K.D. Franco, L.P. Cavalcanti, A. Gasperini,
[99] H.B. Bakrudeen, C. Sudarvizhi, B.S.R. Reddy, Starch nanocrystals based hydrogel: M.I. Alkschbirs, F. Yokaichyia, E. De Paula, G.R. Tfoli, D.R. De Araujo, Poloxamer
construction, characterizations and transdermal application, Mater. Sci. Eng. C 68 407/188 binary thermosensitive hydrogels as delivery systems for inltrative local
(2016) 880889, http://dx.doi.org/10.1016/j.msec.2016.07.018. anesthesia: physico-chemical characterization and pharmacological evaluation,
[100] S.S. Liow, Q. Dou, D. Kai, A.A. Karim, K. Zhang, F. Xu, X.J. Loh, Thermogels: in situ Mater. Sci. Eng. C 68 (2016) 299307, http://dx.doi.org/10.1016/j.msec.2016.05.088.
gelling biomaterial, ACS Biomater. Sci. Eng. 2 (2016) 295316, http://dx.doi.org/ [126] H. Warson, in: F.L. Buchholz, A.T. Graham (Eds.), Modern Superabsorbent Polymer
10.1021/acsbiomaterials.5b00515. Technology, Vol. 49, Wiley-VCH, New York 2000, p. 1548, http://dx.doi.org/10.
[101] Q.Q. Dou, S.S. Liow, E. Ye, R. Lakshminarayanan, X.J. Loh, Biodegradable 1002/1097-0126(200011)49:11b1548::AID-PI482N3.0.CO;2-D (1998, PP
thermogelling polymers: working towards clinical applications, Adv. Healthc. xvii+279, ISBN price 85.00, Polym. Int.).
Mater. 3 (2014) 977988, http://dx.doi.org/10.1002/adhm.201300627. [127] H. Omidian, M.J. Zohuriaan-Mehr, K. Kabiri, K. Shah, Polymer chemistry attractive-
[102] X.J. Loh, S.H. Goh, J. Li, New biodegradable thermogelling copolymers having very ness: synthesis and swelling studies of gluttonous hydrogels in the advanced aca-
low gelation concentrations, Biomacromolecules 8 (2007) 585593, http://dx.doi. demic laboratory, J. Polym. Mater. 21 (2004) 281291.
org/10.1021/bm0607933. [128] A. Seram, C. Tucureanu, D.-G. Petre, D.-M. Dragusin, A. Salageanu, S. Van Vlierberghe,
[103] X.J. Loh, S.H. Goh, J. Li, Hydrolytic degradation and protein release studies of P. Dubruel, I.-C. Stancu, One-pot synthesis of superabsorbent hybrid hydrogels based
thermogelling polyurethane copolymers consisting of poly[(R)-3- on methacrylamide gelatin and polyacrylamide. Effortless control of hydrogel proper-
hydroxybutyrate], poly(ethylene glycol), and poly(propylene glycol), Biomaterials ties through composition design, New J. Chem. 38 (2014) 31123126.
28 (2007) 41134123, http://dx.doi.org/10.1016/j.biomaterials.2007.05.016. [129] L. Yang, Y. Han, P. Yang, C. Wang, S. Yang, S. Kuang, H. Yuan, C. Xiao, Effects of su-
[104] X.J. Loh, Y.X. Tan, Z. Li, L.S. Teo, S.H. Goh, J. Li, Biodegradable thermogelling poly(- perabsorbent polymers on inltration and evaporation of soil moisture under
ester urethane)s consisting of poly(lactic acid) thermodynamics of micellization point source drip irrigation, Irrig. Drain. 64 (2015) 275282.
and hydrolytic degradation, Biomaterials 29 (2008) 21642172, http://dx.doi.org/ [130] V.P. Mahida, M.P. Patel, Synthesis of new superabsorbent poly (NIPAAm/AA/N-
10.1016/j.biomaterials.2008.01.016. allylisatin) nanohydrogel for effective removal of As (V) and Cd (II) toxic metal
[105] J.Y. Zheng, M.J. Tan, P. Thoniyot, X.J. Loh, Unusual thermogelling behaviour of ions, Chin. Chem. Lett. 25 (2014) 601604.
poly[2-(dimethylamino)ethyl methacrylate] (PDMAEMA)-based polymers poly- [131] B. Narjary, P. Aggarwal, A. Singh, D. Chakraborty, R. Singh, Water availability in dif-
merized in bulk, RSC Adv. 5 (2015) 6231462318, http://dx.doi.org/10.1039/ ferent soils in relation to hydrogel application, Geoderma 187 (2012) 94101.
C5RA12816A. [132] L. Wu, M. Liu, Slow-release potassium silicate fertilizer with the function of super-
[106] G. Barouti, S.S. Liow, Q. Dou, H. Ye, C. Orione, S.M. Guillaume, X.J. Loh, New linear absorbent and water retention, Ind. Eng. Chem. Res. 46 (2007) 64946500.
and star-shaped thermogelling poly([R]-3-hydroxybutyrate) copolymers, Chem. [133] K. Sharma, B.S. Kaith, V. Kumar, V. Kumar, S. Som, S. Kalia, H.C. Swart, Synthesis and
A Eur. J. 22 (2016) 1050110512, http://dx.doi.org/10.1002/chem.201601404. properties of poly (acrylamide-aniline)-grafted gum ghatti based nanospikes, RSC
[107] X.J. Loh, V.P. Nam Nguyen, N. Kuo, J. Li, Encapsulation of basic broblast growth fac- Adv. 3 (2013) 2583025839.
tor in thermogelling copolymers preserves its bioactivity, J. Mater. Chem. 21 [134] L. Pan, G. Yu, D. Zhai, H.R. Lee, W. Zhao, N. Liu, H. Wang, B.C.-K. Tee, Y. Shi, Y. Cui,
(2011) 2246, http://dx.doi.org/10.1039/c0jm03051a. Hierarchical nanostructured conducting polymer hydrogel with high electrochem-
[108] S.S. Liow, Q. Dou, D. Kai, Z. Li, S. Sugiarto, C.Y.Y. Yu, R.T.K. Kwok, X. Chen, Y.-L. Wu, ical activity, Proc. Natl. Acad. Sci. 109 (2012) 92879292.
S.T. Ong, A. Kizhakeyil, N.K. Verma, B.Z. Tang, X.J. Loh, Long-term real-time in vivo [135] A.S. Hoffman, Hydrogels for biomedical applications, Adv. Drug Deliv. Rev. 64
drug release monitoring with AIE thermogelling polymer, Small 13 (2017) (2012) 1823.
1603404, http://dx.doi.org/10.1002/smll.201603404. [136] S.K. Siddhanta, R. Gangopadhyay, Conducting polymer gel: formation of a novel
[109] V.P. Nam Nguyen, N. Kuo, X.J. Loh, New biocompatible thermogelling copolymers semi-IPN from polyaniline and crosslinked poly (2-acrylamido-2-methyl
containing ethylene-butylene segments exhibiting very low gelation concentra- propanesulphonicacid), Polymer (Guildf) 46 (2005) 29933000.
tions, Soft Matter 7 (2011) 2150, http://dx.doi.org/10.1039/c0sm00764a. [137] Q. Tang, J. Wu, H. Sun, S. Fan, D. Hu, J. Lin, Superabsorbent conducting hydrogel
[110] Y.-L. Wu, H. Wang, Y.-K. Qiu, X.J. Loh, PLA-based thermogel for the sustained deliv- from poly (acrylamide-aniline) with thermo-sensitivity and release properties,
ery of chemotherapeutics in a mouse model of hepatocellular carcinoma, RSC Adv. Carbohydr. Polym. 73 (2008) 473481.
6 (2016) 4450644513, http://dx.doi.org/10.1039/C6RA08022G. [138] C. Dispenza, C. Lo Presti, C. Belore, G. Spadaro, S. Piazza, Electrically conductive
[111] S.S. Liow, A.A. Karim, X.J. Loh, Biodegradable thermogelling polymers for biomedical hydrogel composites made of polyaniline nanoparticles and poly (N-vinyl-2-pyr-
applications, MRS Bull. 41 (2016) 557566, http://dx.doi.org/10.1557/mrs.2016.139. rolidone), Polymer (Guildf) 47 (2006) 961971.
[112] X.J. Loh, S.H. Goh, J. Li, Biodegradable thermogelling poly[(R)-3-hydroxybutyrate]- [139] S. Nacy, J.M. Razal, G.M. Spinks, G.G. Wallace, P.G. Whitten, Electrically conduc-
based block copolymers: micellization, gelation, and cytotoxicity and cell culture tive, tough hydrogels with pH sensitivity, Chem. Mater. 24 (2012) 34253433.
studies, J. Phys. Chem. B 113 (2009) 1182211830, http://dx.doi.org/10.1021/ [140] Y. Lu, W. He, T. Cao, H. Guo, Y. Zhang, Q. Li, Z. Shao, Y. Cui, X. Zhang, Elastic, conduc-
jp903984r. tive, polymeric hydrogels and sponges, Sci. Rep. 4 (2014).
[113] N. Sahiner, D. Alpaslan, Metal-ion-containing ionic liquid hydrogels and their ap- [141] N. Abu-thabit, Y. Umar, Electrically conductive polyacrylamide-polyaniline
plication to hydrogen production, J. Appl. Polym. Sci. 131 (2014) n/a, http://dx. superabsorbing polymer hydrogels, 1st Int. Electornic Conf. Mater, 1, 2014, pp. 16.
doi.org/10.1002/app.40183. [142] Y. Zhao, B. Liu, L. Pan, G. Yu, 3D nanostructured conductive polymer hydrogels for
[114] X.J. Loh, B.J.H. Yee, F.S. Chia, Sustained delivery of paclitaxel using thermogelling high-performance electrochemical devices, Energy Environ. Sci. 6 (2013)
poly(PEG/PPG/PCL urethane)s for enhanced toxicity against cancer cells, J. Biomed. 28562870.
Mater. Res. A 100A (2012) 26862694, http://dx.doi.org/10.1002/jbm.a.34198. [143] A. Guiseppi-Elie, Electroconductive hydrogels: synthesis, characterization and bio-
[115] X.J. Loh, W. Guerin, S.M. Guillaume, Sustained delivery of doxorubicin from medical applications, Biomaterials 31 (2010) 27012716.
thermogelling poly(PEG/PPG/PTMC urethane)s for effective eradication of cancer [144] K.Y. Lee, D.J. Mooney, Hydrogels for tissue engineering, Chem. Rev. 101 (2001)
cells, J. Mater. Chem. 22 (2012) 21249, http://dx.doi.org/10.1039/c2jm33777k. 18691880.
[116] E. Ye, G.R. Deen, X.J. Loh, Thermogelling copolymers for medical applications, J. Mol. [145] T. Jayaramudu, H.-U. Ko, L. Zhai, Y. Li, J. Kim, Preparation and characterization of
Eng. Mater. 1 (2013) 1330002, http://dx.doi.org/10.1142/S2251237313300027. hydrogels from polyvinyl alcohol and cellulose and their electroactive behavior,
[117] G. Xu, X. Wang, C. Deng, X. Teng, E.J. Suuronen, Z. Shen, Z. Zhong, Injectable biode- Soft Mater. 15 (2017) 6472, http://dx.doi.org/10.1080/1539445X.2016.1246458.
gradable hybrid hydrogels based on thiolated collagen and oligo (acryloyl carbon- [146] D. Pasqui, M. De Cagna, R. Barbucci, Polysaccharide-based hydrogels: the key role
ate)poly (ethylene glycol)oligo (acryloyl carbonate) copolymer for functional of water in affecting mechanical properties, Polymers (Basel) 4 (2012) 15171534.
cardiac regeneration, Acta Biomater. 15 (2015) 5564. [147] A. Uliniuc, M. Popa, T. Hamaide, M. Dobromir, New approaches in hydrogel
[118] Y. Wang, P. Zhang, C.F. Liu, C.Z. Huang, A facile and green method to fabricate synthesisclick chemistry: a review, Cellul. Chem. Technol. 46 (2012) 1.
graphene-based multifunctional hydrogels for miniature-scale water purication, [148] W. Xu, X. He, M. Zhong, X. Hu, Y. Xiao, A novel pH-responsive hydrogel based on
RSC Adv. 3 (2013) 92409246. natural polysaccharides for controlled release of protein drugs, RSC Adv. 5
[119] P. Del Gaudio, F. De Cicco, R.P. Aquino, P. Picerno, P. Russo, F. Dal Piaz, V. Bizzarro, R. (2015) 31573167.
Belvedere, L. Parente, A. Petrella, Evaluation of in situ injectable hydrogels as con- [149] Z. Wei, J.H. Yang, Z.Q. Liu, F. Xu, J.X. Zhou, M. Zrnyi, Y. Osada, Y.M. Chen, Novel bio-
trolled release device for ANXA1 derived peptide in wound healing, Carbohydr. compatible polysaccharide-based self-healing hydrogel, Adv. Funct. Mater. 25
Polym. 115 (2015) 629635. (2015) 13521359.
[120] D. Jaikumar, K.M. Sajesh, S. Soumya, T.R. Nimal, K.P. Chennazhi, S.V. Nair, R. [150] S. Jana, A. Gandhi, S. Kk, B. Sk, Natural polymers and their application in drug de-
Jayakumar, Injectable alginate-O-carboxymethyl chitosan/nano brin composite livery and biomedical eld, J. Pharma. Sci. Technol. 1 (2011) 1627.
hydrogels for adipose tissue engineering, Int. J. Biol. Macromol. 74 (2015) [151] H. Zhang, F. Zhang, J. Wu, Physically crosslinked hydrogels from polysaccharides
318326. prepared by freezethaw technique, React. Funct. Polym. 73 (2013) 923928.
K. Varaprasad et al. / Materials Science and Engineering C 79 (2017) 958971 971

[152] K.T. Shalumon, K.H. Anulekha, S.V. Nair, S.V. Nair, K.P. Chennazhi, R. Jayakumar, So- [164] I. Gibas, H. Janik, Review: Synthetic Polymer Hydrogels for Biomedical Applica-
dium alginate/poly(vinyl alcohol)/nano ZnO composite nanobers for antibacterial tions, 2010.
wound dressings, Int. J. Biol. Macromol. 49 (2011) 247254, http://dx.doi.org/10. [165] O. Goldan, I. Georgiou, G.I.L. Grabov-Nardini, E. Regev, A. Tessone, A. Liran, J. Haik,
1016/j.ijbiomac.2011.04.005. D. Mendes, A. Orenstein, E. Winkler, Early and late complications after a nonab-
[153] F. Camponeschi, A. Atrei, G. Rocchigiani, L. Mencuccini, M. Uva, R. Barbucci, New sorbable hydrogel polymer injection: a series of 14 patients and novel manage-
formulations of polysaccharide-based hydrogels for drug release and tissue engi- ment, Dermatol. Surg. 33 (2007) S199S206.
neering, Gels 1 (2015) 323. [166] L. Dini, E. Panzarini, M.A. Miccoli, V. Miceli, C. Protopapa, P.A. Ramires, In vitro
[154] A.T. Paulino, L.A. Belore, L.T. Kubota, E.C. Muniz, E.B. Tambourgi, Efciency of study of the interaction of polyalkilimide and polyvinyl alcohol hydrogels with
hydrogels based on natural polysaccharides in the removal of Cd 2+ ions from cells, Tissue Cell 37 (2005) 479487.
aqueous solutions, Chem. Eng. J. 168 (2011) 6876. [167] Z. Urbn-Morln, R. Castro-Ros, A. Chvez-Montes, L.M. Melgoza-Contreras, E.
[155] L. Yu, K. Dean, L. Li, Polymer blends and composites from renewable resources, Pin-Segundo, A. Ganem-Quintanar, D. Quintanar-Guerrero, Determination of
Prog. Polym. Sci. 31 (2006) 576602. poloxamer 188 and poloxamer 407 using high-performance thin-layer chroma-
[156] A. Vasconcelos, A.C. Gomes, A. Cavaco-Paulo, Novel silk broin/elastin wound tography in pharmaceutical formulations, J. Pharm. Biomed. Anal. 46 (2008)
dressings, Acta Biomater. 8 (2012) 30493060. 799803, http://dx.doi.org/10.1016/j.jpba.2007.11.027.
[157] R. Silva, B. Fabry, A.R. Boccaccini, Fibrous protein-based hydrogels for cell encapsu- [168] H.R. Patel, R.P. Patel, M.M. Patel, Poloxamers: a pharmaceutical excipients with
lation, Biomaterials 35 (2014) 67276738. therapeutic behaviors, Int. J. Pharmtech. Res. 1 (2009) 299303.
[158] W. Shi, M.-J. Dumont, E.B. Ly, Synthesis and properties of canola protein-based su- [169] L. Du, L. Tong, Y. Jin, J. Jia, Y. Liu, C. Su, S. Yu, X. Li, A multifunctional in situforming
perabsorbent hydrogels, Eur. Polym. J. 54 (2014) 172180. hydrogel for wound healing, Wound Repair Regen. 20 (2012) 904910, http://dx.
[159] A. Pourjavadi, M. Kurdtabar, G.R. Mahdavinia, H. Hosseinzadeh, Synthesis and doi.org/10.1111/j.1524-475X.2012.00848.x.
super-swelling behavior of a novel protein-based superabsorbent hydrogel, [170] N. Das, A Review on Nature and Preparation of Hydrogel Based on Starting Mate-
Polym. Bull. 57 (2006) 813824. rial, Int. J. Pharm. Pharm. Sci. 5 (2013) 5558.
[160] A. Maltais, G.E. Remondetto, M. Subirade, Tabletted soy protein cold-set hydrogels [171] C.M. Hassan, N.A. Peppas, Cellular PVA hydrogels produced by freeze/thawing, J.
as carriers of nutraceutical substances, Food Hydrocoll. 24 (2010) 518524. Appl. Polym. Sci. 76 (2000) 20752079.
[161] R. Caillard, M.A. Mateescu, M. Subirade, Maillard-type cross-linked soy protein [172] J.H. Kim, S.J. Sim, D.H. Lee, D. Kim, Y.K. Lee, D.J. Chung, J.-H. Kim, Preparation and
hydrogels as devices for the release of ionic compounds: an in vitro study, Food properties of PHEA/chitosan composite hydrogel, Work 17 (2004) 21.
Res. Int. 43 (2010) 23492355. [173] S. Akita, K. Akino, T. Imaizumi, K. Tanaka, K. Anraku, H. Yano, A. Hirano, A polyure-
[162] M. Parkes, C. Myant, D. Dini, P. Cann, Tribology-optimised silk protein hydrogels for thane dressing is benecial for split-thickness skin-graft donor wound healing,
articular cartilage repair, Tribol. Int. 89 (2015) 918. Burns 32 (2006) 447451.
[163] N. Annabi, S.M. Mithieux, G. Camci-Unal, M.R. Dokmeci, A.S. Weiss, A.
Khademhosseini, Elastomeric recombinant protein-based biomaterials, Biochem.
Eng. J. 77 (2013) 110118.