Recent insights into polysaccharide-based hydrogels and their potential applications in food sector: a review

Fig. 2. Schematic diagram of hydrogel preparation.
Table 3 
Types of agents used in physical or chemical cross-linking in hydrogel 
preparation.
Hydrogel 
Mediating agent 
Potential applications 
References 
Chemically cross-linked 
Gelatin 
Aldehyde 
Drug delivery (TGF-β1) 
[254] 
PAA/GG graft 
copolymer 
Glutaraldehyde 
Sorbent material for 
chromium ion (Cr (VI)) 
[255] 
PAVA 
EGDMA 
Drug delivery 
[256] 
GC 
Oxidized alginate 
Drug delivery 
[88] 
PE 
Silane 
Electrical wires
Chitosan 
Glutaraldehyde 
Scaffold of hepatocyte 
[257] 
PAA/GG graft 
copolymer 
Glutaraldehyde 
Drug delivery, water 
transportation 
[258] 
AB 
Zinc 
Drug delivery 
[259] 
Agarose and 
chitosan 
Dextrins (oxidized) 
Tissue engineering 
[260]
Physically cross-linked 
PAA 
Antigen-antibody 
mixture 
Drug delivery 
[261] 
Pullulan 
Nanoparticles 
Drug delivery 
[262]
A. Manzoor et al.

---

International Journal of Biological Macromolecules 213 (2022) 987–1006
995
in food industries due to its availability and cost-effectiveness. The 
laccase enzyme is also responsible for the oxidation of phenolic com-
pounds (ferulic acid, tryptophan, and cysteine) through cross-linkage 
formation 
[121]
. Ethylene glycol di-methacrylate (EGDMA), a cross- 
linking agent is used for the synthesis of chemically cross-linked PVA 
from methacrylic acid as a monomer unit in an aqueous medium which 
is thereby used in colorectal cancer for 5-fluorouracil drug delivery 
[122]
. 
Hydrogels are held together by molecular association or physico-
chemical interlinkage such as hydrogen bonds, hydrophobic in-
teractions, charge condensation, or supramolecular chemistry. The 
interactions in this form of the hydrogel are relatively weak. They are, 
nonetheless, numerous and have a role in the occurrence of complicated 
actions. In contrast to covalently bonded materials, hydrogel in-
teractions are extremely dependent on external stimuli (pH, ionic 
strength, solvent composition, or temperature). This allows hydrogels to 
be highly adaptable in terms of the environment 
[123]
. 
C-PVA = Chitosan-Poly vinyl alcohol, PVA = poly vinyl alcohol, PAA 
=
polyacrylamide, GG = guar gum, PAVA = Poly (acrylic-co-vinyl sul-
fonic) acid, GC = Glycol chitosan, PE = Polyethylene, AB = Alginate 
bead, PEG = poly (ethylene glycol), PET = poly (butylene tere-
phthalate), EGDMA = Ethylene glycol dimethacrylate. 
2.2.1. Polymer–polymer crosslinking 
Activated reactive regions of pre-functionalized polymer chains have 
been suggested by many studies as a way to reduce or remove the need 
of small molecule crosslinkers during the hydrogel manufacturing pro-
cess. Hydrogels made via polymer–polymer interaction have many ad-
vantages, but they also have certain drawbacks due to their multi-step 
preparation and purifying process 
[124]
. 
2.2.2. Crosslinking using enzymes 
Enzymes are being utilized to crosslink polymer chains to create 
covalently crosslinked hydrogels. Enzymatically generated PEG-based 
hydrogels are the most prevalent example. The catalytic interaction 
between the carboxamide group and the amine group of lysine is cata-
lyzed by this enzyme, resulting in amide linkage between the polymers 
[125]
. 
2.2.3. Condensation reactions 
Condensation reactions involving functional groups such as –OH or 
–
NH2 with carboxylic acids or derivatives thereof are widely used to 
make polyesters and polyamides chains comprising polymers. Tan et al. 
described a method for making covalently crosslinked alginate and PEG- 
diamines-based gels with better mechanical properties than ionically 
crosslinked hydrogels using EDC 
[126]
. 
2.2.4. High energy irradiation 
Polymer crosslinking with high intensity and energy irradiations can 
also be used to create permanent gels. Gamma and electron beams are 
the most commonly employed of these radiations. They've been utilized 
to successfully polymerize hydrophilic polymers. The vinyl group is 
polymerized to form hydrogels in this way 
[127]
.