Heliyon 6 (2020) e03719

Contents lists available at ScienceDirect

Heliyon
journal homepage: www.cell.com/heliyon

Review article

Commercial hydrogels for biomedical applications

S.H. Aswathy a, U. Narendrakumar b, I. Manjubala a, *
a
Department of Biosciences, School of Biosciences and Technology, Vellore Institute of Technology, Vellore, 632014, India
b
Department of Manufacturing Engineering, School of Mechanical Engineering, Vellore Institute of Technology, Vellore, 632014, India

A R T I C L E I N F O A B S T R A C T

Keywords: Hydrogels are polymeric networks having the ability to absorb a large volume of water. Flexibility, versatility,
Materials science stimuli-responsive, soft structure are the advantages of hydrogels. It is classified based on its source, preparation,
Biomedical engineering ionic charge, response, crosslinking and physical properties. Hydrogels are used in various fields like agriculture,
Nanotechnology
food industry, biosensor, biomedical, etc. Even though hydrogels are used in various industries, more researches
Biotechnology
Hydrogels
are going in the field of biomedical applications because of its resembles to living tissue, biocompatibility, and
Biomedical applications biodegradability. Here, we are mainly focused on the commercially available hydrogels used for biomedical
Commercial products applications like wound dressings, contact lenses, cosmetic applications, tissue engineering, and drug delivery.

1. Introduction 2. Structure of hydrogel

Hydrogels are hydrophilic polymers, with a three-dimensional The solid form of a hydrogel is a network structure of crosslinked
network structure that has the ability to absorb a large volume of polymer chains (Ullah et al., 2015). The molecular weight of the hydrogel
water due to the presence of hydrophilic moieties (Habib et al., 2015). leads to infinity because of its 3D network structure (Rosiak et al., 1995).
The term hydrogel was first coined by Van n Bemmelen in 1984 (van At the molecular level, the most important properties to define the
Bemmelen, 1894). Later in the year 1960, Wichterle and Lim reported hydrogel structure are the mesh size, and the molecular weight of poly-
about hydrogels based on poly (2-hydroxyethyl methacrylate), and they mer chain between the crosslinks (Figure 1) (Ganji et al., 2010). Cross-
suggested hydrogels can be used as filler after enucleation of the eye, linking of hydrogels can be obtained by chemical (covalent) and physical
manufacturing of contact lenses and arteries (Wichterle and Lim, 1960). (hydrogen bonding/entanglement) crosslinks. The swelling of a hydrogel
Since then many number of researches are going on about hydrogels in is mainly defined by the diffusion of water into the hydrogel (Holback
the field of agriculture, food industry, drug delivery, tissue engineering et al., 2011). The hydrogel swelling consist of three stages: 1. primary
and regenerative medicine (Varaprasad et al., 2017). Apart from high bound water-where the water molecules attach to the hydrophilic group,
water absorption capability, it has other properties like flexibility, 2. secondary boundary water-the interaction of water molecules to the
porosity, stimuli-responsive, soft structure and its resemblance to living existing hydrophobic groups and 3. free water-at equilibrium swelling,
tissue (Bahram et al., 2016). Nowadays, scientists have more interest in water is filled into the void spaces (Gibas and Janik, 2010). The rate of
using hydrogel for biomedical applications due to its biodegradability, swelling depends on the concentration of polymer and the crosslinking
biocompatibility, low immunogenicity and ease of usage. By tuning their density (Okay, 2010). The high degree of crosslinking density causes a
physicochemical properties and crosslinking reaction, the hydrogel can decrease in swelling ratio and it increases the brittleness of hydrogel.
be processed as solid, semi-solid and liquid (Varaprasad et al., 2017). As
hydrogel has been a field of research for a few decades, there have been 3. Classification of hydrogels
commercial products of hydrogels finding most applications in the
medical field. In this review, we mainly focus on the various types of Hydrogels are classified based on its source, preparation, ionic
hydrogels, applications and commercial products for wound dressings, charge, response, crosslinking and physical properties (Ullah et al., 2015)
contact lenses, cosmetic applications, tissue engineering, and drug and its further classification is given in a schematic representation in
delivery. Figure 2.

* Corresponding author.
E-mail address: [email protected] (I. Manjubala).

https://doi.org/10.1016/j.heliyon.2020.e03719
Received 18 November 2019; Received in revised form 30 January 2020; Accepted 30 March 2020
2405-8440/© 2020 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
S.H. Aswathy et al. Heliyon 6 (2020) e03719

biomedical applications because their physicochemical or mechanical

properties are tunable and reproducible. Its main disadvantage is the lack
of biocompatibility with some of the polymers.
Poly (ethylene glycol), poly (acrylic acid), poly (ethylene oxide), poly
(vinyl alcohol), etc. are some of the synthetic synthetic polymers used as
hydrogels Ref: (Lee and Mooney, 2001). Physically cross-linked inject-
able PNIPAAm-polyethylene glycol hydrogel improves cellular response,
axonal growth and helps in recovering sensory mortor function. These
fabricated hydrogels could be a suitable candidate for the regeneration of
axons (Bonnet et al., 2020). Polyethylene glycol is a biodegradable,
biocompatible and suitable material for repairing spinal cord injury by
nerve repair and inhibits the degeneration of nerve fiber (Kong et al.,
2017). Further, a polyvinyl alcohol-polyacrylic acid hydrogel can be a
good biomaterial for vascular access with reduced platelet adhesion
(Mannarino et al., 2020). The semi-synthetic polymers include gelatin
Figure 1. Structure of hydrogel at molecular level. methacrylate, cellulose derivatives, etc (S. Utech and Boccaccini, 2016).
Semi-synthetic or hybrid hydrogels are mostly used as they can possess
3.1. Based on source the advantages of both natural and synthetic polymers. The hydrogel
with the combination of synthetic polymer material with natural protein
Based on the source it can be divided into natural, synthetic and gives both mechanical and biological activity. Berkovitch et al. reported
hybrid or semi-synthetic (El-sherbiny & Yacoub, 2013). Hydrogels that the hydrogel fabricated with polyethylene glycol and proteins used
derived from natural sources are a good candidate because of its high for the encapsulation of dorsal root ganglia cells. This hydrogel as shown
biocompatibility but are often limited for its poor mechanical properties in Figure 3 can be used for studying the outgrowth of encapsulated cells
and stability (Singh et al., 2016). Collagen, gelatin, alginate, chitosan, etc by changing the protein and the material rigidity (Berkovitch and
are examples of natural polymers. Chitosan is a biopolymer composed of Seliktar, 2017).
N-acetyl D-glucosamine and D-glucosamine units. Chitosan is formed by
the deacetylation of chitin, which is found in crustacean shells and it is a
polycationic polymer (Croisier and J
er^ ome, 2013). Youming et al. 3.2. Based on composition
fabricated an in situ forming hydrogel based on chitosan and hyaluronic
acid via Schiff base cross-linking reaction. They showed an improved Based on the composition of the polymer, the hydrogel can be divided
cellular response of the material and they suggested that this could be a into homopolymers, copolymer, semi-interpenetrating network, and
suitable biomaterial for abdominal tissue engineering (Deng et al., 2017). interpenetrating network. Homo-polymer hydrogels are composed of the
Natural polymers are also used for making bioinks due to their biocom- same monomer units, where it may have a cross-linked or uncrosslinked
patibility and easy gelation mechanism. A cell encapsulated bioink was network structure based on the basis of monomer nature and polymeri-
fabricated with sodium alginate and collagen or agarose showed good zation technique. Copolymeric hydrogel composed of two or more
bioactivity and mechanical strength (Yang et al., 2017). These three different monomer units with a minimum of one hydrophilic component.
polymers have a great attraction for making bioink because of its low The copolymer-based hydrogel constructed with PLGA-PEG-PLGA is
cytotoxicity and high water content apart from its biocompatibility. capable to solubilize the hydrophobic drug, indomethacin. The solubility
Collagen is the natural extracellular matrix protein that provides cell of the drug is increased when loaded within the copolymer micelles (Qiao
adhesion ligands. Synthetic hydrogels are also a good candidate for et al., 2005). Semi-interpenetrating network hydrogels are formed by the
penetration of one linear polymer chain into another crosslinked polymer

Figure 2. Schematic representation of classification of hydrogels.

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S.H. Aswathy et al. Heliyon 6 (2020) e03719

these two compounds from the semi-IPN hydrogel. The capability of drug
release from the hydrogel proved its use in tissue engineering and other
biomedical applications. Interpenetrating network hydrogel (IPN) is the
most important one, where it is the combination of crosslinked polymers
in network form. In IPN, one polymer is formed or crosslinked in the
presence of another polymer network (Dragan, 2017). Researchers are
showing greater interest in IPN because of its mechanical properties,
mainly the toughness of IPN hydrogel. The mixture of covalently and
ionically crosslinked polymer network gives the toughness of hydrogel
(Bootsma et al., 2017). However, Lin et al. constructed a dual inter-
penetrating network hydrogel using cellulose and polyacrylamide poly-
mers without any covalent bond formation. This IPN structure
incorporated hydrogel shows significantly improved mechanical strength
(Figure 5) (Lin et al., 2018). Puiyan et al. reported that polyethylene
glycol diacrylate and modified gelatin interpenetrating network system
loaded with gold porphyin (AuP) inhibited tumor growth and reduced
angiogenesis in mice bearing human lung cancer xenograft (Lee et al.,
2019).

3.3. Based on configuration

Based on the configuration it can be classified as amorphous, semi-

crystalline and crystalline hydrogel (Mohite and Adhav, 2017). In
1994, semicrystalline hydrogels were developed by chemical cross-
linking method, and it contains both crystalline and amorphous regions.
The physically crosslinked semicrystalline hydrogel was prepared by
micellar and bulk polymerization techniques. Compared to chemically
crosslinked semicrystalline hydrogels, semicrystalline physical hydrogel
have the unique property of changing from solid-state to a liquid state
and vice versa. Therefore, it can be used as injectable hydrogels
andshape-memory hydrogel (Okay, 2018).

Figure 3. Microscopic images of outgrowth of dorsal root ganglia cells on semi 3.4. Based on crosslinking
synthetic hydrogel of PEG incorporated with diferent proteins. Compared to PEG
alone, semi synthetic hydrogels shown better outgrowth of ganglia cells It is generally classified into two types: physical gel and chemical gel
(Adapted from Berkovitch and Seliktar, 2017 with permission). based on the type of crosslinking (Hennink; van Nostrum, 2012). Physical
cross-linking is the most preferred method for the preparation of
network without chemical bonds (Garg et al., 2017). Figure 4 shows a hydrogels. It is also known as reversible gel and it is again subdivided as
semi-interpenetrating network hydrogel of silk fibroin and poly- strong physical gel and weak physical gel. Physical cross-linking mainly
acrylamide was prepared by blending both polymers and used as a matrix occurs through molecular entanglement, hydrogen bonding, hydropho-
for drug release (Mandal et al., 2009). Its properties can be attained by bic association or polyelectrolytic interaction (Hu et al., 2019). Loftipour
varying the polymer concentrations. The FTIC-inulin and trypan blue dye et al. developed a hydrogel by a physical freeze-thaw method using
were used to study in vitro release and it shows a sustained release of chitosan and polyvinyl alcohol polymers. This kind of physical hydrogel
with repeated freeze thaw method provides elastic hydrogel and also
increases the crystallinity of hydrogel. This hydrogel could be used for
healing skin ulcers by incorporating oxytetracycline, an antibiotic and
the hydrogel prepared by three cycles of freeze-thaw containing 5% PVA,
0.75% chitosan, 1000 mg oxytetracycline showed better results of wound
healing (Lotfipour et al., 2019). But it lacks adequate mechanical
strength and stability. To overcome this drawback, researchers mainly
focused on chemical crosslinking. The chemical gel is also called per-
manent gel and it mainly occurs through chemical agents that cross-link
the polymers by covalent interaction (Parhi, 2017). The swelling rate of
chemical gel mainly depends on the concentration of the cross-linking
agent. An acrylic acid-gelatin polymer hydrogel was constructed by
free radical polymerization which is chemically cross-linked with
ethylene glycol dimethacrylate with the help of initiator ammonium
persulphate. The ability of swelling behaviour depends on the concen-
tration of polymer, monomer and the cross-linking agent. As the con-
centration of polymer and crosslinker increases, the rate of the swelling
Figure 4. Semi-interpenetrating network made up of polyacrylamide polymer
and silk fibroin chains Incorporation of fibroin improves the elasticity and ratio is decreased (Majid et al., 2015). Recently, researchers have focused
softness of the hydrogel and helps in sustained release of drug (A) Schematic on developing in situ formed hydrogels for biomedical applications such
representation of formation of SF/PAAm semi-IPN network hydrogels (B) as injectable gels, drug delivery, surgical glue, etc. The chemical process
Typical appearance of different SF/PAAm semi-IPN hydrogels after removing behind the in-situ formation of hydrogel includes enzymatic
from moulds (Adapted from Mandal et al., 2009 with permission). cross-linking, Schiff base cross-linking, Michael addition, click chemistry

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S.H. Aswathy et al. Heliyon 6 (2020) e03719

Figure 5. The compression behaviour of cellulose hydrogel (yellow), Cellulose-polyacrylamide IPN hydrogel (red) and Polyacrlamide hydrogel. Only in IPN hydrogels
showed good mechanical integrity after deformation (Adapted from Lin et al., 2018 with permission).

and photo-cross-linking (Ko et al., 2013). An in situ forming injectable pH 1.2 and pH 7.4, as the swelling takes place at pH 7.4 and deswelling at
hydrogel can encapsulate cells and growth factors by simple methods. pH 1.2 (Xu et al., 2018). The properties of thermosensitive hydrogels are
An in situ forming injectable hydrogel fabricated using tyramine controlled by the equilibrium between hydrophilic and hydrophobic
conjugated hyaluronic acid via enzymatic cross-linking with horseradish moieties (Chai et al., 2017). PNIPAAm- poly (N-isopropylacrylamide) is
peroxidase (HRP) and galactose oxidase. HRP usually catalyzes the the commonly used thermoresponsive hydrogels that can undergo
crosslinking reaction with oxidizing agent hydrogen peroxide but it is changes in volume due to slight temperature variations. The hydrophi-
having fast gelation rate. To avoid this drawback, here they used addi- licity or hydrophobicity of PNIPAAm hydrogel considerably changes at
tional enzyme galactose oxidase to produce hydrogen peroxide (Wang their lower critical solution temperature (Matsumoto et al., 2018). Shuo
et al., 2020). Rachel et al. studied morphology and functionalities of rat et al. described that the temperature-responsive poly (N-iso-
Schwann cells, C2C12 skeletal muscle cells and spinal spheroids from propylacrylamide) crosslinked with 4, 40 -dihydroxybiphenyl diacrylate
human induced pluripotent stem cells cultured on microbial trans- can be used for different applications (Tang et al., 2017). In the field of
glutaminase (mTg) crosslinked gelatin-laminin hydrogel. Enzyme mTg smart hydrogels, shape memory and self-healing hydrogels are the
catalyzes the construction of N-e-(gamma-glutamyl) lysine amide bonds advanced stimuli-responsive hydrogels (Echeverria et al., 2018).
(Besser et al., 2019). The cell adhesion and proliferation behaviour of
osteoblast and fibroblast cells were studied on in situ forming Michael 4. Applications of commercial hydrogel
type addition crosslinked thiolated glycol chitosan hydrogel with oligo
(acryloyl carbonate)-b-poly (ethylene glycol)-b-oligo (acryloyl carbon- Due to the flexibility and versatility, hydrogels are used in many fields
ate). The reaction was carried out in PBS of pH 7.4 at 37
C. The in vitro extending from industrial to biological. Major applications of hydrogel
results showed this hydrogel is not supported for cell adhesion but the include biomedical, dyes removal, heavy metal ions removal, agriculture,
hydrogel functionalized with Gly-Arg-Gly-Asp-Cys residues showed bet- sanitary diapers, pH-sensors, biosensors, and supercapacitors (Bahram
ter cell adhesion. This modified hydrogel could be a good matrix for et al., 2016). In this review, we only focused on biomedical applications
tissue engineering applications (Y. Yu et al., 2011). Park et al. developed such as wound dressings, cosmetics, contact lenses, drug delivery, and
a chondrogenic differentiation factor (cytomodulin) contained in situ tissue engineering.
forming click cross-linked hyaluronic acid hydrogel for cartilage repair.
After activated the carboxylic group present in hyaluronic acid, it was 4.1. Wound dressings
then modified with tetrazine and transcyclooctene and it was taken in a
dual-barrelsyringe, upon injection hydrogel was formed by click-based Wound dressings are materials mainly polymers in the form of gauzes,
reaction (Figure 6) (Park et al., 2019). gels, hydrogels, hydrocolloids etc. Among them, hydrogels are the most
Apart from conventional hydrogels, there is another unique type of promising approach in wound healing. Hydrogels act as an ideal wound
hydrogel is called “smart hydrogels”. It will respond to various stimuli dressing as they can provide a moist environment in the wound site, helps
such as light, temperature, pH, ionic strength or electric field, etc. and in the removal of wound exudates, prevents infection and gives a suitable
can cause changes in their swelling behavior, structure and mechanical environment for tissue regeneration (Gupta et al., 2011).
properties (El-sherbiny & Yacoub, 2013). A smart pH-responsive A wound is an injury that happens in body tissues either inside or
hydrogel fabricated with acrylic acid, N-isopropylacrylamide and poly outside, mainly in skin due to trauma, cut or any other damage (Basu
(L-lactide)-co-polyethyleneglycol-co-poly (L-lactide) dimethacrylates as et al., 2017). The wound can cause the disruption of the structure and
a crosslinker can be used for dual drug delivery system. For example, the function of normal tissue. There are two types of wounds; acute and
hydrogel can be loaded with doxorubicin and tetracyclin and release at chronic wounds. Acute wound heals completely in a shorter time while

Figure 6. Schematic representation of in situ forming click based Hyaluronic acid hydrogel This hydrogel helps in retention of cytomodulin which induces the
condrogenic differentiation (Adapted from online open access article Park et al., 2019 with permission).

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the chronic wound takes a longer time to heal. The process of wound wound healing in vivo (Ribeiro et al., 2013). Chitosan is an excellent
healing includes hemostasis, inflammation, proliferation, and remodel- wound healing material because of its haemostatic nature (Ahmed and
ling (Whitney, 2005). The wound healing process gets affected by various Ikram, 2016). A physically cross-linked chitosan hydrogel has the ability
reasons such as wound infection, depth of the wound, foreign body to reconstruct the skin of third-degree burn, where they tested in pig
interaction, stress, pressure, age, diseases, etc (H. Liu et al., 2018). dorsal area (Viton et al., 2007). An injectable hydrogel constructed via
Scarring occurred during normal healing due to the deposition of disulphide bond cross-linking of thiolated polyethylene glycol and silver
collagen fibers and it will be there for a long time. With the help of wound nitrate. This hydrogel is loaded with desferrioxamine, an angiogenic drug
dressings, scarless healing occurs. Catanzano et al. developed a com- and this could repair the diabetic wound with its angiogenic activity
posite hydrogel containing alginate and hyaluronan for the wound (Figure 7) (Chen et al., 2019).
healing process. Alginate is a polysaccharide having high absorption To avoid wound-related diseases and scarring, there is a wide range of
capacity which helps in minimize wound secretions and promote wound hydrogel related wound care products are available in the market.
healing by maintaining a moist environment. With the help of hyaluronic Amorphous gel, hydrogel sheets, hydrogel film, and hydrogel impreg-
acid which helps in keratinocyte migration and proliferation, they suc- nated gauze are the different types of hydrogel wound dressing available
cessfully prepared alginate-hyaluronan hydrogel through ionic cross- in the market (Figure 8). The ActivHeal® hydrogel is one of the wound
linking (Catanzano et al., 2015). Polysaccharide based hydrogel has care dressing available in the market and is used for primary wound
greater potential in wound healing application because of its high water dressing (AlTabbaa and Ankrah, 2016). This is an amorphous gel used in
absorption ability. A nanocellulose incorporated hemicellulose hydrogels the dry wound with low exudate where it slowly increases the moisture
were prepared by Jun et al. This hydrogel helps in adhesion and prolif- content level in the wound environment and promotes moist wound
eration of fibroblast cells and it can be a suitable hydrogel material for healing through autolytic debridement. And it induces the growth of
wound healing (J. Liu et al., 2016). epithelial cells. This hydrogel is used for various wounds from pressure
In wound dressing applications, anti-bacterial and anti-inflammatory ulcers, cavity wounds, leg ulcers, diabetic ulcers, post-surgical wounds,
hydrogels have a good impact. A multifunctional and pH-responsive and abrasions. Suprasorb® G hydrogel is also used for acute or chronic
composite hydrogel made of carboxylated agarose and tannic acid, wounds with low exudate in dry wounds. This gel gently removes
which is ionically crosslinked with zinc salts for wound healing (Ninan necrotic tissue and absorbs it into the gel (“Lohmann-Rauscher website,
et al., 2016). The pH-responsive property of carboxylated cellulose ”). Wound healing by this hydrogel is also by autolytic debridement with
combined with anti-microbial, anti-inflammatory, anti-oxidant property moisture donation to the wound environment. The moist environment
of tannic acid showed increased compressive strength and anti-bacterial provides granulation and epithelisation to the wound surface. The main
activity. Dextran is another polysaccharide used for synthesizing advantages are it reduce wound pain and its ease of usage. It is used with
hydrogel. It helps in situ gelation and controlled release of immobilized secondary film dressing to secure hydrogel. Acrylic polymers, poly-
growth factor with the help of chitosan microparticles and showed better ethylene, and phenoxyethanol are the main components of Suprasorb® G

Figure 7. Improved healing of diabetic skin wound using drug loaded thiolated PEG hydrogel compared to control (Adapted from opne access article Chen et al., 2019
with permission).

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S.H. Aswathy et al. Heliyon 6 (2020) e03719

Figure 8. Different forms hydrogel wound dressing available in market. (a) Neoheal® hydrogel sheet used for wound dressing, (b) Amorphous gel that can be sued for
necrotic wounds and burns, (c) - Hydrogel film and (d) Hydrogel impregnated gauze (Image Courtesy: (a) Kikgel, Poland, (b) Avery Dennison Medical, Longford,
Ireland-(Finesse Medical Ltd) (c) Lohmann & Rauscher GmbH & Co, Germany and (d) McKesson Medical Supplies).

hydrogel. AquaDerm™ (“Dermarite website,”a) and DermaSyn® (“Der- (Aderibigbe and Blessing Atim, 2018, Ahmed and Ikram, 2016, Al-sabah
marite website,” n.d.-b) are the product of DermaRite, where Aqua- et al., 2019, Alba-Bueno et al., 2009, Besser et al., 2019). Purilon® gel
Derm™ is the hydrogel sheet dressing and DermaSyn® is the hydrogel (“Coloplast website,“) is a hydrogel which contains naturally derived
wound dressing. The functions of both hydrogels are same as that of the components like calcium alginate and sodium carboxymethyl cellulose.
previously described hydrogel, where the DermaSyn is the non-oily And it does not contains any additives. Apart from leg ulcers, pressure
amorphous gel enriched with vitamin E. ulcers, etc. it can be used for first and second-degree burns. This gel
NU-GEL™ (“Systagenix website,” n.d.) hydrogel is a cost-effective, should be used with secondary wound dressings. The presence of car-
transparent, and amorphous gel. This hydrogel contains sodium algi- boxymethyl cellulose in the hydrogels helps in maintaining an optimal
nate which effectively removes damaged tissue and slough. It also creates moist environment due to high water holding capacity. It also helps in
the moist in the wound environment for healing. The alginate present in extracellular matrix formation and re-epithelization (Wong and Ramli,
the gel increases the absorptive capacity. The alginate hydrogels have 2014).
been used as wound dressing material because of its high water content, Neoheal® Hydrogel wound dressings produced by Kikgel manufac-
permeability, and elasticity (W. Yu et al., 2016). It has the potential to turer (“Kikgel website,”). It is a primary hydrogel dressing made up of
reduce bacterial infections and also promote hemostatic properties both natural and synthetic polymers such as agar, polyethylene glycol,

Table 1. Commercially available hydrogel wound dressings.

Product name Company name Hydrogel form/Composition Application Ref

Suprasorb® G Lohmann & Hydrogel film made up of Dry wounds, Lower leg ulcer, (“Lohmann-rauscher website,”)
Rauscher Global acrylic polymers, polyethylene, pressure ulcer, first and
and phenoxyethanol with second-degree burns, scalds
70% water content.
AquaDerm™ DermaRite industries Hydrogel sheet consist of Pressure ulcers, Minor burns and (“Dermarite website,” a)
2-Acrylamido-2 methyl-1 radiation tissue damage
propanesulfonic acid sodium,
Propylene Glycol, Poly (ethylene
glycol) dimethacrylate,
2-Hydroxy-2-methylpropiophenone
with 38–55% water
DermaGauze™ DermaRite industries Hydrogel impregnated gauze Acute or chronic partial and (“Dermarite website,” c)
dressing. Acrylate polymer is the full thickness wounds
one of the component in DermaGauze.
Neoheal® Hydrogel Kikgel Hydrogel sheet consist of PEG, Ulcers, abrasions, burns, bed (“Kikgel website,”)
polyvinylopyrrolidone, and agar sores and other chronic wounds
and it is crosslinked via electron beams.
Contains about 90% of water.
Simpurity™ Hydrogel Safe n’Simple Absorbent sheets containing polyethylene Dry wounds, skin (“Wound source website,”)
oxide, polyvinyl alcohol, acrylate, burns and dry scabs
polyurethane, and purified water
Restore Hydrogel Hollister Incorporated Hydrogel impregnated gauze pad contains Partial and full (“Hollister website,”)
hyaluraonic acid and promote thickness wound
wound healing by autolytic debridement.

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S.H. Aswathy et al. Heliyon 6 (2020) e03719

Table 2. Commercially available hydrogel wound dressings in gel form.

Product name Company name Composition Applications Ref

ActivHeal® Advanced Medical It is a primary wound Pressure ulcers, leg ulcers, (AlTabbaa and Ankrah, 2016)
Solutions Ltd. dressing contains 85% water. diabetic foot ulcers,
cavity wounds
DermaSyn® DermaRite industries It's a primary wound Acute or chronic partial (“Dermarite website,”-b)
dressing contains vitamin E. and full thickness wounds
NU-GEL™ Systagenix Contains sodium alginate Chronic wound, diabetic foot (“Systagenix website,”)
which effectively debrides ulcers, venous leg ulcers
necrotic tissue and fibrinous slough. and pressure ulcers.
Purilon® Coloplast Contains calcium alginate and Leg ulcers, pressure ulcers, (“Coloplast website,“)
sodium carboxymethyl cellulose non-infected diabetic foot
with purified water. ulcers and First and
second degree burns
INTRASITE◊ Gel Smith and Nephew Consist of Carboxymethyl Pressure ulcers, (“Smith and Nephew website,”)
cellulose and propylene glycol. Diabetic foot ulcers
Surgical incisions
Venous ulcers
SOLOSITE◊ Gel Smith and Nephew Contains sodium salt of carboxymethyl Minor burns, cuts, abrasions, (“Smith-Nephew Website,”)
cellulose and glycerol with skin tears, Venous ulcers,
above 60% water. Surgical incisions, Diabetic
foot ulcers, Pressure ulcers,
Woun'Dres® Coloplast It contains the polymers like Dry wounds (“Coloplast Website,“)
carbomer and collagen with
other ingredients.

and polyvinylpyrrolidone. And this hydrogel is crosslinked via electron compared with the wound exposed to air without scab (George D Winter,
beams. This is having enough mechanical strength due to crosslinking. 1962).
The main advantage is that it contains about 90% of water and it has the
capability to absorbing and donating water to the wound environment. It 4.2. Cosmetic applications
also induces the granulation and epidermisation. Commercially available
hydrogel wound dressings like film, sheets and hydrogel incorporated The major function of the skin is to protect the body from environ-
gauze are depicted in Table 1 and gel form in Table 2. From all the mental factors such as microorganisms and UV radiation. Besides it also
products we can understand that all those promote moist wound healing, helps in maintaining the body temperature and body fluid (Papakon-
where it enhanced autolytic debridement. The moist wound healing was stantinou et al., 2012). Hydration of the skin is important in the main-
first described by George D Winter. From his experiments, he concluded tenance of its appearance and texture (Verdier-S
evrain and Bont
e, 2007).
that the epithelization of the superficial wound under moist is twice as Natural aging, due to the genetic factors and photoaging, due to sun

Table 3. Different types of hydrogel cosmetic products available in market.

Product name Manufacturer Hydrogel form/Characteristics Application Ref

Rose soothing Moira Face Mask made with sodium Face Skin (“Moira website,”)
hydrogel mask polyacrylate, glycerine, cellulose
gum, water etc. with maximum
absorption. Soothes and
rejuvenate the skin
Collagen Hydrogel Dr. Derm Hydrogel contains sea collagen Face Skin (“Bulgaria website,”)
Professional and hyaluronic acid. Nourishes,
regenerate the skin of the face
Advanced G
enifique Lancome Paris Hydrogel face mask made up Face Skin (“Lancome website,”)
Hydrogel Mask of glycerine, polyacrylate-13,
water etc. enriched with Bifidus
extract. Skin will become
moisturized, radiant, smoother
and looks healthy glow
Charcoal Hydrogel ELF cosmetics Under Eyemask contains water, Under eye skin (“Elf cosmetics website,”)
under eye mask charcoal, seaweed extract, etc.
Nourishes and gives a healthy
glow to the skin.
Lip patch Taiki Hydrogel patch contains Lip (“Taiki cosmetics website,”)
sodium hyaluronate and glycerine
for moisturizing. Strong adhesion
and gives lips elastic and hydrated
Aloe vera supple skin hydrogel Images Sheet mask contains Hyaluronic Face (“Images website,”)
acid, glycerol, water etc. Moisturizes,
nourishes, smooths the skin and also
gives elasticity and firmness to the skin.
Neutrogena® Hydro Boost® Johnson and Face mask contains hyaluronic acid. Face (“Neutrogena website,”)
Johnson Provide instant and long lasting
moisture to the skin.

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S.H. Aswathy et al. Heliyon 6 (2020) e03719

hydration to the skin (Papakonstantinou et al., 2012). Table 3 shows the

commercially available hydrogels for cosmetic applications.

4.3. Contact lens

Contact lens gets direct contact with the eye to correct the vision,
drug delivery for ophthalmic conditions and cosmetic use (Farandos
et al., 2015). There are two major types of contact lens, rigid and soft
contact lens. Rigid contact lenses are made with polymer polymethyl
methacrylate (PMMA). It has properties like surface wettability, high
modulus of elasticity with excellent durability. But it has no oxygen
permeability and which also causes eye effects (Geiges, 2001). In 1960,
Wichterle and Lim have first described hydrogel for the use of contact
lens and other applications (Wichterle and Lim, 1960). A hydrogel sys-
Figure 9. Properties or requirements suitable for hydrogel as contact lenses. tem based on Poly (2-hydroxyethyl methacrylate) (pHEMA) was the first
hydrogel material used to make a contact lens. Poly (vinyl alcohol),
polyacrylonitrile, etc. are the hydrophilic polymers that have been
investigated for making hydrogel contact lenses Ref: (Lai et al., 2014).
exposure serves as major reasons for skin damage apart from climatic
Besides this, silicone and fluorine-based hydrogel contact lens are also
conditions and pollution exposure (Baumann, 2007). Cosmetics products
investigated. But silicone-based hydrogel contact lenses are one of the
are used to enhance skin appearance and texture. Moisturizers, body
most dominant hydrogel material today (Musgrave and Fang, 2019). A
lotions, skin cleaners are some of the cosmetic items used for maintaining
soft or hydrogel contact lenses should have properties like high water
the body. Nowadays, the cosmetics industries showing more interest in
content, their ability to transfer water and oxygen permeability (Mun
can
hydrogels due to properties like biocompatibility, elasticity, softness and
et al., 2016). Oxygen permeability is a very important characteristic of
high water content.
the proper functioning of the cornea. Because cornea uses oxygen from
The hydrogel can be used for skin issues such as cellulite, wrinkles,
the air to maintain its structure, function, and clarity (Nicolson and Vogt,
pigmentation, skin hydration and aging. Caffeine-containing bioadhesive
2001). The oxygen permeability of hydrogel contact lenses is critically
hydrogel used for cosmetic applications mainly cellulite or gynoid lip-
related to the water content and thickness of the contact lens (McMahon
odystrophy. The bioadhesive property of hydrogel helps in releasing
and Zadnik, 2000). Apart from this, it should be biocompatible, comfort
caffeine gradually into the skin thereby enhancing skin appearance and
to wear, continuous tear film for clear vision, permeable to ions for
texture (Parente et al., 2015). Kim et al. developed a liposome in a
maintaining movement, non-irritable and resistant to tear film accumu-
hydrogel complex system for delaying photoaging, where it enhanced the
lation (Figure 9). Luminous transmittance and refractive index are the
skin permeation of drugs. The skin permeation of drugs was improved
important requirements for hydrogel for making contact lenses (Cal
o and
through the hydrogel system, which helps in loosening the skin barrier
Khutoryanskiy, 2015). The extended use of conventional hydrogel con-
through skin hydration (Kim et al., 2014). In the market, hydrogel
tact lenses can cause hypoxia on corneal physiology and corneal integrity
products such as face mask, lip mask, under eye pad, etc. are available for
and function. The high oxygen permeability capacity of silicone-based
treating skin related issues. Collagen hydrogel (“Bulgaria website,“) by
soft contact lens can avoid these types of adverse corneal effects. But
Dr. Derm professional is a hydrogel used as a cosmetic product, which
silicone-based hydrogel contact lens can also have the potential of
helps in regenerate and to restore the softness, elasticity and hydration of
causing corneal homeostasis with extended use (Stapleton et al., 2006).
the skin. This hydrogel is made up of hyaluronic acid and collagen. Hy-
The hydrogel contact lens is available in the market on the basis of
aluronic acid plays an important role in skin moisture by giving
daily wear, biweekly wear, monthly contacts, and light adaptive contact.

Table 4. Commercially available soft contact lenses.

Product name Manufacturer Characteristics Applications Ref

Airsoft™ Maxvue vision Silicone hydrogel Astigmatism (“Maxvue vision website,”)
material with high
water content and
oxygen permeability.
Gentle 59 Mark'ennovy Bioinspired Short sight and long sight (“Markennovy website,”)
silicone hydrogel lens.
Clariti® 1 day CooperVision® Silicone hydrogel with Short sight and long sight (“Cooper vision Website,“)
high oxygen permeability.
Keep eyes moist by attracting
water molecules to the lens.
Miacare™ 1 day BenQ Silicone hydrogel with Myopia (“Miacare Website,”)
ultra-high oxygen permeability.
Contains Hyaluronic acid and
sodium alginate as moisturizing agents.
Soflens daily disposable Bausch & Lomb Keep eye comfortable by Short and Long sightedness (“Bausch and Lomb Website,“)
giving moisture around the lens.
Focus® DAILIES® with Ciba Vision Lubricates the eye for every blink. Astigmatism (“Cibavision Website,“)
AquaRelease™
ACUVUE OASYS® Johnson& Maintain moisture, tear film Presbyopia (“Acuvue Website,“)
Johnson and reduce dryness.
everclear™ ELITE Visco Vision Flexible silicone hydrogel Long sightedness (“Visio direct Website,”)
with high oxygen permeability.

8
S.H. Aswathy et al. Heliyon 6 (2020) e03719

Figure 10. Commercially available hydrogel implant for drug delivery (a) Cervidil® that contains 10 mg of dinoprostone in a hydrogel and, (b) SUPPRELIN® LA, a
subcutaneous implant (Image courtesy: (a) Ferring Pharmaceuticals Inc. USA, (b) Endo Pharmaceuticals, USA.

Bausch and Lomb in 1971 launched the first hydrogel contact lens to the second method is the formed hydrogel is immersed in drug solution
market Lai et al., 2014). Today Bausch and Lomb is one of the most (Mishra et al., 2017). The main disadvantages of hydrogel drug delivery
popular soft contact lens manufacturers. SofLens Daily disposable, Ultra system are their low tensile strength and difficulty in loading hydro-
Contact lens, PureVision2 HD, iconnect and New Biotrue® are the soft phobic drugs (Hoare and Kohane, 2008). To increase the loading effi-
contact lens produced by Bausch and Lomb for short and ciency of hydrophobic drugs to the hydrogel matrix is by the
long-sightedness (“Bausch and Lomb website,”-a). They also produced incorporation of molecules that have the ability to form inclusion com-
contact lenses such as SofLens Daily Disposable toric, SofLens Toric and plexes and incorporation of hydrophobic moieties (Larra~ neta et al.,
PureVision 2 for astigmatism (“Bausch and Lomb website,”-b) and 2018). Molecular imprinting of supermolecular hydrogels increases the
SofLens Multifocal, Bio true ONEday lens and Pure Vision 2 for presby- drug loading efficiency without affecting the release kinetics (Juric et al.,
opia (“Bausch and Lomb website,”-c). Like this, manufacturers such as 2019). Diffusion-controlled, swelling controlled, and chemically
Johnson & Johnson, CooperVision, Ciba vision, etc. are producing controlled are the drug release models for the controlled release of drug
different types of soft contact lenses for different applications. Some of from hydrogel (Sri and Chatterjee, 2014).
the products are depicted in Table 4. Francisco et al. studied the shape Hydrogel drug delivery system can be used for ophthalmic, vaginal,
changes in cornea induced by hydrogel contact lenses, specifically first transdermal, subcutaneous, oral, rectal applications, etc. Anda et al.
and second-generation hydrogel CLs. They reported that there are reported that the nitrosalicyl-imine-chitosan hydrogel system loaded
changes in topological indices like anterior corneal astigmatism, surface with diclofenac sodium salt provides sustained delivery for local
regularity index, and mean keratometry those who are using Soflens 38 therapy (Craciun et al., 2019). Poloxamer, a block copolymer hydrogel
and these indices are stable where those who are using Focus Night & loaded with tetramethylpyrazine (TMP) were studied for the
Day and Acuvue Oasys hydrogel CLs (Alba-Bueno et al., 2009). Biotrue™ controlled drug delivery. Poloxamer is compatible with both hydro-
solution manufactured by Bausch and Lomb contains Hyaluronan which philic and hydrophobic drugs. In this study they reported that the
can be used for conditioning agent for contact lenses irrespective of its release rate of the drug was reduced due to TMP is wrapped in micelles
water content (Scheuer et al., 2010). and the release rate is increased as the temperature increases (Xia,
2019). Another study reported that paclitaxel-loaded thermo-sensitive
in situ forming hydrogel may be used to inhibit local tumor reap-
4.4. Drug delivery pearance at tumor resection site (Shive, Bichara, Berrada, &
Ruel-garie, 2004).
The process of administering a drug to the human or animal body to Cervidil® (Ferring Pharmaceuticals Inc.) is a hydrogel vaginal
achieve a desired therapeutic effect is known as drug delivery (Tiwari insert used to prepare the cervix for delivery (“Iodine Website,”). It
et al., 2012). The drug delivery system should deliver the drug in a contains dinoprostone also known as prostaglandin E2, it has an
controlled manner and it should release the drug at an effective rate to important role in cervical ripening. After insertion, the dinoprostone
the targeted site (Sandeep, SL, & Kanupriya, 2012). There is an releasing rate is 0.3 mg/h from the total concentration of 10mg.
increasing interest in using hydrogel as a drug delivery system due to its SUPPRELIN® LA (Endo Pharmaceuticals Inc.) (www.fda.gov/med-
three-dimensional structural network with high water holding capacity. watch, 2017) is a subcutaneous implant, used for the treatment of
This property of hydrogel supports in holding drugs and release the drug central precocious puberty. It is a hydrogel polymer reservoir con-
in a controlled manner. The high amount of water present in hydrogel taining 50 mg histrelin acetate drug in a small flexible tube. It delivers
helps in encapsulate hydrophilic drugs (Li and Mooney, 2016). The the drug at the rate of 65 mcg per day by diffusion controlled manner
sustained release of the drug is achieved by its physical properties such as over 12 months. Figure 10 showing the commercially available
porosity (Narayanaswamy and Torchilin, 2019). The drug is loaded on hydrogel implant for drug delivery. There is only a limited number of
the hydrogel by two methods. In the first method, the polymer is mixed products are available in the market.
with drug followed by polymerization along with crosslinker and the

9
S.H. Aswathy et al. Heliyon 6 (2020) e03719

Figure 11. Morphological evaluation of GelrinC after implanted in patient. Faster regeneration of cartilage was achieved by using GelrinC implant Series of proton
density fat suppressed images in coronal plane show development of cartilage transplant in follow-up examinations after (a) 1 week; (b) 6 months; (c) 12 months; and
(d) 24 months. Arrows and circle delineate RT area (Adapted from Trattnig et al., 2015 with permission).

4.5. Tissue engineering Injectable hydrogels are more advantageous than normal hydrogel scaf-
folds owing to its easy filling of irregular defects and it does not require
Tissue engineering is an interdisciplinary field that combines various complex surgical procedures. Xiao et al. described that in situ
fields like material science, cell biology, and engineering to repair cross-linkable hyaluronan hydrogel can be used for tissue engineering
damaged tissues (O'Brien, 2011). The aim of tissue engineering is to purposes. Hyaluronan is the extracellular matrix constituent, where it
produce scaffolds that can mimic the extracellular matrix for tissue helps in cell adhesion, proliferation, and differentiation (Shu et al.,
regeneration. A scaffold material should have an interconnected porous 2004). Polyethylene glycol-modified with RGD motifs which is an in situ
structure for the cell ingrowth, nutrients transport, waste removal and it photopolymerized injectable hydrogels for bone tissue engineering
should have mechanical strength that mimics the native tissue. Besides, (Burdick and Anseth, 2002).
the scaffolds should also have biocompatibility, biodegradability, steril- Gelrin C™ (Regentis Biomaterial Ltd.) is a photocrosslinked hydrogel
ity and to provide structural support for the cell attachment, proliferation made up of polyethylene glycol and human fibrinogen protein. This is a
and differentiation (Cascone and Lamberti, 2019). There are different non-porous injectable hydrogel, which is being evaluated for knee
approaches for constructing scaffolds, which include premade porous cartilage regeneration (Figure 11) (Trattnig et al., 2015). This product is
scaffolds, decellularized extracellular matrix, cell sheets with secreted now under clinical trial. Mebiol® Gel PNIPAAm-PEG 3D Thermo
extracellular matrix and cell encapsulated in self-assembled hydrogel reversible hydrogel (Cosmo Bio co ltd.) is the commercially available
(Chan and Leong, 2008). Hydrogels gained great interest in tissue engi- hydrogel for stem cell culture, cell implantation, organ or tissue regen-
neering due to its resemblance to the native extracellular matrix. There eration, drug delivery, and non-cell culture applications (“Cosmobio
are several approaches for hydrogel scaffold fabrication including Website,”). The Mebiol® hydrogels can be only used for research pur-
lyophilization, emulsification, solvent casting – leaching, gas foaming – poses. It is a thermoreversible sol-gel that remains in the gel state at high
leaching, photolithography, microfluidic, micro molding and 3D printing temperature and transforms into a liquid state at a low temperature. The
(El-sherbiny & Yacoub, 2013). main features of Mebiol® are easy handling, biocompatible, and highly
Hydrogels scaffolds are used in the regeneration of cardiac tissues, transparent for cell observation. Qiang Li et al. reported that, by using
cartilage, and bone. Ayesha et al. reported that hydrogel based on this thermoreversible three dimensional hydrogel may be used for
nanocellulose and sodium alginate crosslinked with calcium chloride can culturing cells to produce proteins for the therapeutic purpose (Q. Li
be used for cartilage tissue engineering (Al-sabah et al., 2019). Another et al., 2018). HyStem® Hydrogel UV Quick Set Kit (ESI BIO) is the hy-
study reported that gelatin-based hydrogel reinforced with eggshell aluronic acid UV light-controlled system which supports
particles, where it helps in the differentiation of pre-mature cells into three-dimensional cell culture for tissue engineering purposes and 3D
osteoblast (Wu, Stroll, Lantigua, Suvarnapathaki, & Camci-unal, 2019). printing applications (“Esibio Website,”). Corning® Matrigel® matrix

10
S.H. Aswathy et al. Heliyon 6 (2020) e03719

(Corning Incorporated Life sciences) is a hydrogel, which mimics the Additional information
natural extracellular matrix used as a model for 2D and 3D cell culture
experiments (“Corning Website,”-a). Corning® PuraMatrix™ peptide No additional information is available for this paper.
hydrogel (Corning Incorporated Life sciences) is another hydrogel used
for 3D cell culture. It is mainly composed of water (99%) with 1% of Acknowledgement
amino acids. It is used for stem cell proliferation, tumor cell migration
and invasion, and in vivo analysis of tissue regeneration (“Corning The authors SHA and IM gratefully acknowledge the support from
Website,” n.d.-b). Bioglex Ltd. producing various products includes Bio- DST project on hydrogels (DST/SERB/EMR/2017/003504).
gelx™-S, Biogelx™-RGD, Biogelx™-IKVAV, Biogelx™-YIGSR, and Bio-
gelx™-GFOGER (“Biogelx Website,”). These are synthetic peptide References
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biomedical. It is clear that there is a long way to go in research on -for-nearsighted-farsighted.
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hydrogel in biomedical applications especially for tissue engineering and es-for-astigmatism.
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Bausch and Lomb Website.. http://www.bausch.in/our-products/contact-lenses/lenses-fo
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temperature and for sustained release of the drug. The other applications regulate neuronal morphogenesis. Int. J. Pharm. 523 (2), 545–555.
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sive impact on hydrogel-based research for drug delivery. In tissue en- Bootsma, K., Fitzgerald, M.M., Free, B., Dimbath, E., Conjerti, J., Reese, G., Sparks, J.L.,
gineering fabrication technique is very important, nowadays, more 2017. 3D printing of an interpenetrating network hydrogel material with tunable
researches are based on in situ crosslinked hydrogel. Cathal et al. viscoelastic properties. J. Mech Behav. Biomed. Mater. 70, 84–94.
Bulgaria website, Retrieved August 8, 2019, from, https://www.cosmeticsbulgaria.com/
developed a biopen, which can be used for in situ fabrication of hydrogel en/product/collagen-hydrogel-for-face-dr-derm-professional/.
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2016). Although extensive studies have been done on hydrogels in tissue modified PEG hydrogels for bone tissue engineering. Biomaterials 23, 4315–4323.
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Author contribution statement Chai, Q., Jiao, Y., Yu, X., 2017. Hydrogels for biomedical applications: their
characteristics and the mechanisms behind them. Gels.
Chan, B.P., Leong, K.W., 2008. Scaffolding in tissue engineering: general approaches and
All authors listed have significantly contributed to the development tissue-specific considerations. Eur. Spine J. 17.
and the writing of this article. Chen, H., Cheng, R., Zhao, X., Zhang, Y., Tam, A., Yan, Y., Shen, H., Zhang, Y.S., Qi, J.,
Feng, Y., Liu, L., Pan, G., Cui, W., Deng, L., 2019. An injectable self-healing
coordinative hydrogel with antibacterial and angiogenic properties for diabetic skin
wound repair. NPG Asia Mater. 11, 3. https://doi.org/10.1038/s41427-018-0103-9.
Funding statement Cibavision Website. http://www.cibavision.com.my/lenses/focus_ dailies/focus_dail
ies.shtml.
Coloplast Website. https://www.coloplast.us/woundres-collagen-hydrogel-1-en-us.aspx.
This work was supported by Science and Engineering Research Board Connell, C.D.O., Di Bella, C., Thompson, F., Augustine, C., Beirne, S., 2016. Development
(SERB), India (EMR/2017/003504). of the Biopen: a handheld device for surgical printing of adipose stem cells at a
chondral wound site. Biofabrication 8 (1).
Cooper vision Website.. https://coopervision.com/contact-lenses/clariti-1-day.
Corning Website. (n.d.-a). https://www.corning.com/in/en/products/life-sciences/pro
Competing interest statement ducts/surfaces/matrigel-matrix.html.

The authors declare no conflict of interest.

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