Gels or hydrogels are described as the matrix of cross-linked polymers. Hydrogels are naturally a part of the body in the form of collagen,
gelatin, mucous, tear films, cartilage, vitreous humor, cornea, and tendon. Collagen, gelatin, and nanofillers can be used to modify the strength of
hydrogels. Use of biodegradable hydrogel scaffold is ideal for tissue regeneration, where the scaffold degrades as the tissue regeneration occurs.
The hydrogel can be lone or composition of fundamental properties such as edible, non-edible, biodegradable, non-biodegradable, injectable,
topical, natural, synthetic, physically crosslinked, chemically cross-linked. During past three decades hydrogels due to various factors such as
biodegradable, absorbent, tissue resemblance and easy use, have received the enormous attention from researchers around the globe. Although
hydrogels have become part of a variety of industries but quest for biomedical application of hydrogels is ongoing. This review addresses the
recent advances in different forms of hydrogels and their biomedical use.
Researchers are working on hydrogels over decades and according
to researchers a water-swollen, network of cross-linked
polymers produced by the reaction between one or more monomers
or by hydrogen bonding or by large van der Waals interaction
between chains [1-3]. It has also been reported that the hydrogel
is a superabsorbent material that absorbs water over 99% of its
capacity without dissolving itself and swells to form a gel called
hydrogel [2,3]. The hydrogel is a colloidal material involving disperse
phase and dispersion medium combined to yield a semisolid
material like jelly [4]. Over 70 years ago the process of methacrylic
acid polymerization was patented [5], and now hydrogels are existing
in a variety of forms. In the biomedical field, the hydrogels have
entered in the mainstream due to interesting porous structure, biocompatibility
and easy of production [6,7].
The hydrogel can be lone or combinations of different source,
composition, charge, and structure [1]. Hydrogels are broadly classified
as chemical and physical hydrogels by their crosslinking ability
[1]. Chemical crosslinking involves the conversion of hydrophobic
polymers into the hydrophilic polymeric gel to form a network
with the aid of crosslinking agents. However, the crosslinking agent
can often be toxic and cannot be used in the biological application.
Hence their removal is required before its implementation in bio
logical systems [3,7]. Chemically cross-linked hydrogels can be pre
pared either by high irradiation energy or by photo-polymerization
[1]. Physically cross-linked gels do not possess toxicity like chemically
cross-linked gels. Mechanism of physically cross-linked gel
formation is a molecular entanglement or use of secondary force
such as ionic interaction, hydrogen bonding, crystallization, hydrophobic
interaction and protein interaction [3,8].
Hydrogels are widely used in the field of drug delivery, tissue
engineering, regenerative medicine, food industries as well as fashionable
showcase materials providing safety cushion and identity
to the biomedical device [9,10]. In pharmaceuticals, the peptide,
MIP, nanofiller enhanced hydrogels are being considered as drug
delivery system [11,12]. Designing of the biomaterial surface can
turn the material into smart biomaterial, and this surface modulation,
e.g., for cell adhesion[13], chemo-selective conjugation of biologicals
[14], etc. are gaining more attention of researchers in fields
like material science as well as bioscience [9]. Swelling nature of
the gels mainly depends on their network structure, but the latter
part is significantly related to the condition under which the gel has
formed [15].
Hydrogels have become omnivorous, the pharmaceutical, nutraceutical,
agricultural, medical devices and cosmetic industries have formulations or developing formulation based on hydrogels
(Table 1). Modulation of material surface with stimuli-responsive
polymers can show considerable changes in properties in response
to various stimuli’s [9,10]. Use of such stimuli-responsive polymers
in hydrogel preparation can make it stimuli-responsive hydrogel
and such hydrogel can undergo considerable change in their structure
upon a small change in external environment; such hydrogels
are called as stimuli-responsive hydrogels [9]. These environmental
changes could be changed in pH, temperature, light and hormonal
secretion and have different applications mentioned further in
Table 1.
Table 1: Hydrogels and their biomedical applications
Tissue regeneration and drug delivery are the focused applications
of peptide-based hydrogels [16]. Supramolecular structure
of the peptides capable of self-gelation (gelating peptides) can be
used to deliver and control the release of the drugs physiological
conditions [17-20]. Peptide-based hydrogel as cochlear implants
describes the advancement of hydrogels in biomedical applications
[21,22]. Recent findings point the possibility of the peptide-based
hydrogels as functionalized biomaterials scaffold to attract projections
from neurons, its attachment and stability providing an uninterrupted
interface between cochlear implants and audio-neurons
[21]. Peptide-based hydrogels can mimic extracellular matrix
(ECM), where the peptides and related derivatives self-assemble
to form a gel [23,24]. During early 90’s Zhang et al. described that
peptides can be staggered using their structure, for example, ionic
bonds formed between alanine side chains facing each other and
the charged lysine and glutamic acid chains facing each other [25].
These hydrophilic/hydrophobic nanosheets then form a fibrous hydrogel
in the presence of salts [21].
Moreover, even the shortest peptide comprised of natural amino
acids found capable of creating the transitional α-helices inside
hydrophilic environment as well as self-assembled into fibrous
structure [26]. Use of peptide-based hydrogels has begun for nutraceutical
purposes too [27-29]. Molecularly imprinted polymer
(MIP) based hydrogels are getting popular in biomedical applications
as smart hydrogels systems [24]. The MIP based hydrogels
are non-covalently bonded hydrogels formed by hydrogen bonding
between the monomer and imprint template [24]. The imprints of
the MIPs formed as a result of template monomer interaction [30].
The application of this system involves recognition of target molecules
at the molecular level [31]. Precisely, the claims of these MIPs
prominently associated with microfluidic devices [32,33].
Addition of nanofillers can substantially influence material’s
mechanical, optical and thermal properties [34]. Based on the dimensions
the nanofillers can be classified as one dimensional, e.g.,
clay nanoplates [35], two dimensional, e.g., nanofibers (nanotubes
and nanofibers) [36] and three dimensional, e.g., metallic nanoparticles
[34,37]. Clay nanoplates or nanoclays are the basic nanofillers
to be used in the hydrogels and can be natural, e.g., montmorillonite
[38], or synthetic, e.g., hydrotalcite [34]. Clays are used as catalysts,
absorbents, metal chelating agents as well as polymer nanocomposites
to make the hydrogel mechanically stronger than conventional
hydrogels [39]. The water absorption is controlled with the
inclusion of clay nanofillers in the hydrogels for wound dressing
[40]. However, other nanostructures like carbon nanotubes (CNT)
and graphene are one of the novel nanofillers to be used in hydrogels
[41,42]. Both graphenes, as well as CNT, are being studied for
their use in tissue engineering as well as in drug delivery [42];
moreover, it can be used to coat the electrodes in solar cell operated
medical devices [43]. Similarly, graphene-enhanced hydrogel
actuators [44], a small amount of graphene could increase the conductivity
four times benefiting conductive tapes [45,46], element
sensor [47].
Super absorbent hydrogels are another example of smart hydrogels.
Swelling of hydrogel could result in complications in case
of implants, but the superabsorbent hydrogels withstand the swelling
[48,49]. Super absorbent hydrogels can also be referred as super
porous hydrogels [49]. Hydrophilic polymers can adsorb water
up to 90 % of their weight without dissolving. This property of hydrogels
has been addressed for dressings for wound healing, e.g., alginate-based hydrogel dressing [50]. The research on collagen
product has broadened in past two decades, and the collagen-based
hydrogel is part of that development [51]. The skin, bone, cartilage,
tendon, and vasculature are the different collagen [51]. The
network of collagen fibers and related components is recognized
as ECM [52]. Although collagen itself is water-insoluble, it can be
blended with other hydrophilic polymers to form hydrogels scaffolds
mimicking skin, bone, etc. [53]. Multilayered collagen hydrogel
can be prepared for retaining the cellular functions [54]. Moreover,
collagen hydrogels have found less toxic compared to many
others and most efficient in proliferation [7]. The inclusion of polysaccharides
like Beta-glucan (beta-1,6-branched beta-l,3-glucan)
has been reported biocompatible and effective in encouraging cell
growth as well as rejuvenate the collagen [55].
Hyaluronic acid (HA) is a polysaccharide-based component of
the natural ECM [3]. Hydrophilic nature of the HA helps in water
binding, but on the other side, HA has a short half-life of 1-2 days
due enzymatic degradation and over-hydration [56]. HA could be
low molecular weight or high molecular weight [6]. However, the
low molecular weight HA renders the cell functions and could develop
cancer [57]. On the other side, high molecular weight HA is
nonimmunogenic, aids in nutrient transportation as well penetration
of fibers, cells, and vesicles [58]. HA-based implants have
promising results, e.g., CNS scaffold implantation aids neural rejuvenation
[59], elastic nature of HA reduces bone friction [60-80],
HA gel filler restores skin elasticity and gives uniformity [56].
Hydrogels have become one of the essential and vital players
of biomedical sector. Since chemically cross-linked hydrogels are
toxic, the physically cross-linked hydrogels are in demand. Hydrogels
based on peptides, HA, acrylamide are patented and marketed.
However, the quest for monomers and cross-linkers will remain to
invent and modify biological applications of hydrogels [81-89].
ISSN: 2574 -1241
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