226
G. Keerthiga et al.
Oxime crosslinking reaction requires an amino-oxy/hydroxylamine group and a
functional aldehyde or ketone. These reactions are highly specific and occur even
in the presence of other functional groups. It offers an advantage of crosslinking
at the acidic condition and the only by-product being water. Self-healing, oxime
cross-linked hydrogel can undergo reversible gel-sol conditions at acidic conditions
[31].
Michael addition is a simple reaction between nucleophiles (donor) and activated electrophilic alkene or alkynes (acceptor). Often referring to thiol-containing
polymers are added to the α and β unsaturated carbonyl polymers under necessary conditions that are well suited for the formulation of a cellular scaffold, gene
transfection, and tissue replacements [124, 158].
iv. Covalent chemistry crosslinking
Reversibility of crosslinking helps to develop self-healing hydrogel that maintains strong integrity and internal annuity. This property of physical crosslinking is
extended to covalent bonding. For example, boronate esters prepared from boronic
acids and 1,2- and 1,3-diols that are pH-responsive, and it is designed based on its
pKa (Hydrogel formation is favored when pH > pKa; remains as an aqueous solution when pH < pKa). Polymers such as PEG, polyphenols such as ellagic acid,
epigallocatechin gallate (EGCG), and tannic acid (TA) were modified with linkers to
provide boronate ester bonds for gelation at pH 7.4 that promote self-healing property at the physiological environment [77]. Native enzymes such as cytochrome-c
can also be incorporated into hydrogel by structural integration to provide controlled
stimuli-responsive hydrogel [178].
3 Hydrogel Design
Biomedical applications of the hydrogel are highly depended upon the bulk structure
and parameters such as polymer volume in the swollen state (v 2, s ), the molecular
weight of the polymer chain between two crosslinks (Mc) and its corresponding
mesh size (ξ). The measured quantity of water imbibed and retained by the hydrogel
is given as polymer volume fraction. As random polymerization occurs, molecular
weight between two crosslinks (physical/chemical) is calculated as average value
(M c ) in the hydrogel. The correlation distance between adjacent crosslinks is also an
average quantification that gives a measure of space existing between the polymer
chains in the hydrogel. These parameters are related to each other, and dependent
on the nature and charge of the polymer, type of crosslink, which measured both
theoretically and experimentally [105, 104]. Two prominent theories widely used to
explain configuration of the hydrogel are [149]:
1. Equilibrium—swelling theory.
2. Rubber—elasticity theory.
G. Keerthiga et al.
Oxime crosslinking reaction requires an amino-oxy/hydroxylamine group and a
functional aldehyde or ketone. These reactions are highly specific and occur even
in the presence of other functional groups. It offers an advantage of crosslinking
at the acidic condition and the only by-product being water. Self-healing, oxime
cross-linked hydrogel can undergo reversible gel-sol conditions at acidic conditions
[31].
Michael addition is a simple reaction between nucleophiles (donor) and activated electrophilic alkene or alkynes (acceptor). Often referring to thiol-containing
polymers are added to the α and β unsaturated carbonyl polymers under necessary conditions that are well suited for the formulation of a cellular scaffold, gene
transfection, and tissue replacements [124, 158].
iv. Covalent chemistry crosslinking
Reversibility of crosslinking helps to develop self-healing hydrogel that maintains strong integrity and internal annuity. This property of physical crosslinking is
extended to covalent bonding. For example, boronate esters prepared from boronic
acids and 1,2- and 1,3-diols that are pH-responsive, and it is designed based on its
pKa (Hydrogel formation is favored when pH > pKa; remains as an aqueous solution when pH < pKa). Polymers such as PEG, polyphenols such as ellagic acid,
epigallocatechin gallate (EGCG), and tannic acid (TA) were modified with linkers to
provide boronate ester bonds for gelation at pH 7.4 that promote self-healing property at the physiological environment [77]. Native enzymes such as cytochrome-c
can also be incorporated into hydrogel by structural integration to provide controlled
stimuli-responsive hydrogel [178].
3 Hydrogel Design
Biomedical applications of the hydrogel are highly depended upon the bulk structure
and parameters such as polymer volume in the swollen state (v 2, s ), the molecular
weight of the polymer chain between two crosslinks (Mc) and its corresponding
mesh size (ξ). The measured quantity of water imbibed and retained by the hydrogel
is given as polymer volume fraction. As random polymerization occurs, molecular
weight between two crosslinks (physical/chemical) is calculated as average value
(M c ) in the hydrogel. The correlation distance between adjacent crosslinks is also an
average quantification that gives a measure of space existing between the polymer
chains in the hydrogel. These parameters are related to each other, and dependent
on the nature and charge of the polymer, type of crosslink, which measured both
theoretically and experimentally [105, 104]. Two prominent theories widely used to
explain configuration of the hydrogel are [149]:
1. Equilibrium—swelling theory.
2. Rubber—elasticity theory.