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Synthesis of PVA/PVP based hydrogel for biomedical applications: a review

Article in Energy Sources, Part A: Recovery, Utilization and Environmental Effects · July 2018
DOI: 10.1080/15567036.2018.1495786

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Environmental Effects

ISSN: 1556-7036 (Print) 1556-7230 (Online) Journal homepage: http://www.tandfonline.com/loi/ueso20

Synthesis of PVA/PVP based hydrogel for

biomedical applications: a review

Mohamed Saad Bala Husain, Arun Gupta, Basma Yahya Alashwal & Swati
Sharma

To cite this article: Mohamed Saad Bala Husain, Arun Gupta, Basma Yahya Alashwal & Swati
Sharma (2018) Synthesis of PVA/PVP based hydrogel for biomedical applications: a review,
Energy Sources, Part A: Recovery, Utilization, and Environmental Effects, 40:20, 2388-2393, DOI:
10.1080/15567036.2018.1495786

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ENERGY SOURCES, PART A: RECOVERY, UTILIZATION, AND ENVIRONMENTAL EFFECTS
2018, VOL. 40, NO. 20, 2388–2393
https://doi.org/10.1080/15567036.2018.1495786

Synthesis of PVA/PVP based hydrogel for biomedical applications: a

review
Mohamed Saad Bala Husain, Arun Gupta, Basma Yahya Alashwal, and Swati Sharma
Faculty of Chemical & Natural Resources Engineering, Universiti Malaysia Pahang, Gambang, Pahang, Malaysia

ABSTRACT KEYWORDS
The composition and synthesis of hydrogel were developed by using Polyvinyl Biocompatible; biomedical
alcohol (PVA) and Polyvinylpyrrolidone (PVP). Polyvinyl alcohol (PVA) and applications; hydrogel; PVA;
Polyvinylpyrrolidone (PVP) based hydrogels are the most popular water-solu- PVP
ble, biodegradable, biocompatible, non-carcinogenic, and extremely low cyto-
toxicity synthetic polymers due to their good biocompatibility have been used
in numerous biomedical applications, such as implants, artificial organs, drug
delivery devices, and wound dressings. In this review paper, details of synthetic
of hydrogel formulations with PVA and PVP for biomedical applications.

Introductions
Hydrogels are three-dimensional, hydrophilic, polymeric networks capable of absorbing large amounts
of water or biological fluids. Due to their high water content, porosity and soft consistency, they closely
simulate natural living tissue, more so than any other class of synthetic biomaterials (Caló and
Khutoryanskiy 2015). The hydrophilicity of the network is due to the presence of hydrophilic groups
such –NH2, –COOH, –OH, –CONH2, –CONH–, and –SO3H, capillary effect and osmotic pressure
(Kołodyńska et al. 2016). On another side, its polymer network structure can be formed by chemical
cross-linking, physical cross-linking or both simultaneously. The chemical nature, network morphology
and equilibrium swollen state of hydrogels are responsible for several important properties such as
mechanical strength and internal and external transport (Van Tomme, Storm, and Hennink 2008).
Hydrogels of many synthetic and natural polymers have been produced with their end use mainly in
tissue engineering, and the pharmaceutical and biomedical fields (Montoro, De Fátima Medeiros, and Alves
2013). A list of hydrogels with their proposed corresponding applications is shown in Table 1 (Gulrez, Al-
Assaf, and Phillips 2011).

Classifications of hydrogels
The hydrogels can be classified on bases of source, preparation method, electric charge, configuration,
cross-linking and, functions as shown in Table 2. Also, the classification of hydrogel depending on their
stability characteristics, and “intelligent” or conventional depending on their ability to exhibit significant
dimensional changes with variations in pH, temperature, or electric field (Mark 2013).

Physically cross-linked
In recent years, there has been increasing interest in physically crosslinked gels. The main reason is that the
use of crosslinking agents in the preparation of such hydrogels is avoided (Ebara et al. 2014). Hydrogels are

CONTACT Arun Gupta arungupta10@gmail.com Faculty of Chemical & Natural Resources Engineering, Universiti Malaysia
Pahang, Gambang, Pahang 26300, Malaysia
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/ueso.
© 2018 Taylor & Francis Group, LLC
 ENERGY SOURCES, PART A: RECOVERY, UTILIZATION, AND ENVIRONMENTAL EFFECTS 2389

Table 1. Applications of hydrogel with types of polymers.

Application
Wound care
Drug delivery, pharmaceutical
Dental Materials
Technical products (cosmetic,
pharmaceutical)
Injectable polymeric system
Tissue engineering, implants
Agriculture, waste treatment,
separation, etc.
Polymers
Polyurethane, Poly(Ethylene Glycol), Poly(Propylene Glycol), Poly(Vinylpyrrolidone),
Polyethylene Glycol And Agar Xanthan, Methyl Cellulose, Carboxymethyl Cellulose, Alginate,
Hyaluronan And Another Hydrocolloid.
Poly(Vinylpyrrolidone), Starch, Poly(Vinylpyrrolidone), Poly(Acrylic Acid), Carboxymethyl
Cellulose, Hydroxypropyl Methylcellulose, Polyvinyl Alcohol, Acrylic Acid and, Methacrylic
Acid.
Hydrocolloids (Ghatti, Karaya, Kerensis gum).
Starch, Gum Arabic, Xanthan, Pectin, Carrageenan, Gellan, Welan, Guar Gum, Locust, Bean
Gum, Alginate, Heparin, Chitin, and Chitosan.
Polyesters, Polyphosphazene, Polypeptides and, Chitosan.
Polyvinyl Alcohol, Polyacrylic Acid, Hyaluronan and, Collagen.
Starch, Xanthan, Polyvinyl Alcohol, Polyvinyl Methyl Ether) and, Poly(N-isopropylacrylamide).

Table 2. Classifications of hydrogels.

Classification Contents References
Source Natural and synthetic (Kumbar, Laurencin, and
Deng 2014)
Polymeric composition Homo-polymeric hydrogels, copolymeric hydrogels, and multipolymer (Ahmed 2015)
interpenetrating polymeric hydrogel
Preparation method Simultaneous polymerization crosslink of polymer (Dumitriu 2001)
Electric charge Non-ionic (neutral), ionic, amphoteric electrolyte (ampholytic) and, (Ahmed 2015)
zwitterionic.
Configuration Amorphous (non-crystalline), semi-crystalline and, crystalline. (Ahmed 2015)
Cross-linking Covalent bond and intermolecular force (Dumitriu 2001)
Functions Biodegradable, stimuli-responsive, superabsorbent and etc (Dumitriu 2001)

synthesized by ionic interaction, crystallization, amphiphilic block and graft copolymers, hydrogen bond
and protein interaction (Hennink and Van Nostrum 2012).

Crystallization
Crystallization of polymers has also been used to form physically cross-linked gels such as poly(vinyl
alcohol) (PVA). Physically cross-linked PVA gels were obtained by exposing PVA aqueous solution
to repetitive freezing-thawing cycles, which induced crystallization and resulted in a network
hydrogel structure (Ebara et al. 2014).

Hydrogen bond
Hydrogen bonding interactions can also be used to form physically crosslinked gel-like structure
(Ebara et al. 2014). Hydrogels can be synthesized at low pH (Kalia and Sabaa 2013). A method for
the improvement of the physical and mechanical strength of keratin hydrogel materials is by
increasing the hydrogen bonds of the hydrogel (Vestberg et al. 2017). The hydrogen bonding of the
hydrogel can be increased between the keratin protein chains or between the keratin and other
polymers such as polyvinyl alcohol and polyvinylpyrrolidone (Dou et al. 2015). Hydrogen bonds
are formed only if the protonation of carboxylic acid groups occurs which shows pH-dependent
swelling of the gels (Akhtar, Hanif, and Ranjha 2016).

Ionic interaction
Ionic interactions between polymer chains provide an alternative to covalent cross-linking due to their high
binding constants and the unique swelling properties of the resulting hydrogels (Loh 2014). In this process,
2390 M. S. B. HUSAIN ET AL.

Hydrogels can be cross-linked under mild conditions, at room temperature and physiological pH (Alvarez-
Lorenzo and Concheiro 2013). Ionic hydrogels can be obtained from both synthetic precursor polymers and
from biopolymers (Rossow and Seiffert 2015).

Amphiphilic block and graft copolymers

Hydrogels formed by hydrophobic association are based on either amphiphilic blocks or graft
copolymers which contain distinct segments of hydrophobic and hydrophilic nature (Demirci and
Khademhosseini 2016).

Protein interaction
The protein interactions that occur between chains determine film network formation and properties
(Iannace and Park 2015). simple hydrogel system based on protein-protein interactions with easily
tunable their physical properties (Kawai and Hashizume 2017).

Chemically cross-linked
Chemically crosslinked hydrogels can be formulated by radical polymerization of monomers in the
presence of cross-linkers, a reaction of functional side groups of polymers with themselves or other
functional cross-linkers, high-energy irradiation and enzyme reaction (Shi et al. 2017). Hydrogels
formed through chemical bonds, such as covalent bonds, are permanent and irreversible (Zhang,
Fisher, and Leong 2015). Several strategies exist in order to obtain a cross-linked network (Van
Hoorick et al. 2016). Chemically cross-linked gels can be obtained by radical polymerization of low
molecular weight monomers in the presence of cross-linking agents, the chemical reaction of
complementary groups, and high-energy irradiation (Zhang, Fisher, and Leong 2015).

Cross-linking by radical polymerization

The integral components of the hydrogels synthesis are the monomer, initiator and cross-linker for the
hydrogels prepared by radical polymerization (Mishra, Vats, and Clark 2015). Aside from radical
polymerization of mixtures of vinyl monomers, chemically crosslinked hydrogels can also be obtained
by radical polymerization of polymers derivatized with polymerizable groups (macromonomer) Figure 1
(Ebara et al. 2014). In general, hydrogels can be prepared from free radical polymerization with tunable
mechanical properties and variable gel thicknesses by modulating the polymer chain length, cross-
linking density, and reaction times (Jaegle et al. 2017). Polymerization is usually initiated by free-radical
generating compounds such as benzoyl peroxide, 2,2-azo-isobutyronitrile (AIBN), and ammonium
peroxide sulphate or by using UV-, gamma- or electron beam-radiation (Caló and Khutoryanskiy 2015).

Cross-linking by reaction of complementary group

A lot of water-soluble polymers are characterized by the presence of functional groups including
−
OH, −COOH, and −NH2. Interestingly, these functionalities can be applied to cross-link the
polymer chains by reacting them with complementary reagents. For example, amines can react
quite easily with carboxylic acids using conventional carbodiimide coupling chemistry to generate
such as gelatin hydrogels (Van Hoorick et al. 2016).

Cross-linking by high energy irradiation

Cross-linking by high-energy irradiation High-energy irradiation can be applied to produce cross-
linked hydrogels by irradiating a polymer solution containing vinyl functionalities (Van Van
 ENERGY SOURCES, PART A: RECOVERY, UTILIZATION, AND ENVIRONMENTAL EFFECTS 2391

Figure 1. Chemically cross linked hydrogels by radical polymerization (Ebara et al. 2014).

Hoorick et al. 2016). The mechanical properties of the hydrogels could be further improved by
irradiation in a deaerated atmosphere with high energy radiation (Cooper et al. 1995).

Cross-linking by enzymatic reaction

Crosslinking of polymers to form hydrogels can be performed in the presence of enzymes. This type of
crosslinking is beneficial for hydrogel formation because of the mild activity of the enzymes (Dutta 2016).

Advantages of hydrogel as dressings

The following advantages of hydrogel dressings for wound management have been identified
(Frehner and Watts 2016):

● Promote a moist wound bed to facilitate granulation and epithelisation.

● Rehydrate dry wounds to provide a moist wound bed.
● Encourage autolytic debridement where appropriate through maintenance of a moist wound
environment.
● The conformable characteristics of amorphous hydrogel dressings maximize.
● Contact between the dressing and the wound bed in smaller wounds. This reduces the
formation of dead space inside the wound where bacteria can flourish.
● Subject to the type and consistency of the hydrogel, the dressing may be left in situ for several
days on noninfected wounds.
● Transparent gel sheets allow wound inspection without disturbing the dressing.
● Unless dried, easily removed without traumatising the wound and surrounding skin (sheet dressings).
● Reduce pain due to moisture maintenance and the cooling effect of the hydrogel.

Disadvantages of hydrogel as dressing

The following disadvantages of hydrogel dressings have been specified (Kamoun, Kenawy, and Chen 2017).
2392 M. S. B. HUSAIN ET AL.

● Semi-transparent.
● Semi-permeable to gases and water vapor.
● Poor bacterial barrier.
● Sometimes poor mechanical stability.

Polymers based hydrogel as dressing

Polymers are today the largest group of materials used for biomedical purposes. The biological synthetic
polymers such as Polyvinyl alcohol (PVA), and poly(N-vinylpyrrolidone) (PVP), have been widely studied
but their properties need to be improved further for specific medical applications (Kamoun et al. 2015)
Polyvinyl alcohol (PVA) based hydrogel is one of the well-known polymer gel that due to its good
biocompatibility, has been used in numerous biomedical applications, for example as implants,
artificial organs, contact lenses, drug delivery devices, and also wound dressings in wounds manage-
ment (Kokabi, Sirousazar, and Hassan 2007). because of easy preparation, excellent chemical
resistance, and physical properties. But it has poor stability in water because of its highly hydrophilic
character. Therefore, to overcome this problem PVA should be insolubilized by copolymerization,
grafting, cross-linking, and blending (El-Mohdy and Ghanem 2009). Strangely enough, both soft/
hard keratin protein was not blended with PVA as wound dressing membranes, it might due to it’s a
very hard solubility compared to PVA. However, it was utilized as wound healing agent, due to its
supporting for fibroblasts formation and easy absorbing heavy metal ions and volatile organic
compounds for skin regeneration (Kamoun, Kenawy, and Chen 2017).
Poly-vinylpyrrolidone (PVP) is one of the most popular water-soluble, biodegradable, biocompatible,
and extremely low cytotoxicity synthetic polymers (Kamoun et al. 2015). It is used in many biomedical
applications and separation processes to increase the hydrophilic character of the blended polymeric
materials (El-Mohdy and Ghanem 2009). Other pharmaceutical applications of PVP include its use as a
matrix or as an additive for the controlled release of drugs for the coprecipitation of other drugs and as a
solid dispersion for controlling drug diffusion. A recent work has described the use of PVP for topical
applications onto the skin for the transdermal delivery of drugs. The combination of the properties of
PVA and PVP in PVA/PVP blends has emerged as a new tool for the preparation of biomaterials (Seabra
and De Oliveira 2004). PVA/PVP based hydrogel has been prepared by using the γ-irradiation technique.
The physical properties were found that the gel fractions increases with increasing irradiation dose while
the swelling of PVA/PVP blended hydrogels nearly tends to increase with increasing PVP content and
reduced with enhanced irradiation doses (El-Mohdy and Ghanem 2009).

Conclusion
Polyvinyl alcohol (PVA) and Polyvinylpyrrolidone (PVP) are a highly versatile method to improve
the mechanical property of the hydrogels. also, are not toxic compounds and environmental friendly.
thus, PVA and PVP based hydrogels are important for biomedical applications.

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