hydrogels prepared from G1 and G2 could self-heal at acidic and basic environments
and did not self-heal under neutral environment which validates the fact that both
dynamic reactions involved in cross-linking were kinetically locked at neutral
pH. However, addition of catalytic amount of aniline in hydrogel precursors was
accelerating acylhydrazone dynamic reaction at neutral pH. Eventually, each of the
healed gels was found to be resistive toward stretching by a tweezer at the end of
healing process (Fig. 30b).
In 2015, Wei et al. synthesized a double-network (DN) self-healing hydrogel with
dynamic imine and acylhydrazone bonds coexisting in the cross-linked architecture
[75]. Hydrogel was prepared by mixing oxidized sodium alginate (OSA) solution
with N-carboxyethyl chitosan (CEC) and adipic acid dihydrazide (ADH) solution at
room temperature with different pH environments (PBS pH 7.0 or 6.0). Continuous
step strain measurements performed to assess the self-healing property of gels
suggested immediate recovery of their storage G
0 and loss moduli G
00 . In the same
year, Yu et al. reported a hyaluronic acid-based DN hydrogel cross-linked via the
Diels-Alder reaction and acylhydrazone bonds for tissue engineering applications
[76]. To fabricate the gels, two sets of HA derivatives were obtained: one
functionalized with furan and adipic dihydrazide (HA-furan-ADH) and the other
with furan and aldehyde (HA-furan-CHO) groups. Hydrogels were obtained by
mixing HA-furan-ADH and HA-furan-CHO in deionized water and cross-linked
via covalent acylhydrazone bond in several minutes. Thereafter, difunctionalized
PEG-maleimide (MAL-PEG-MAL) was added to the mixture to obtain DN through
the Diels-Alder cycloaddition reaction (Fig. 31a). To examine the mechanical
properties of self-healed hydrogels, compressive stress-strain tests were conducted
on original and healed hydrogels. Results demonstrated that both gels possessed
similar stress-strain curves (Fig. 31b). Standard DMA (dynamic mechanical analysis) test was used to compare the toughness of DN hydrogels with SN (only
acylhydrazone) and revealed that storage modulus G
0 of DN gel was significantly
higher than SN gel (Fig. 31c). Additionally, visual self-healing experiments were
carried out where samples were cut into two halves and put in contact for 3 h at
ambient temperature, and thus healed DN gel sample stood its own weight and
resisted pulling (Fig. 31d).
In 2017, Yang et al. reported a cellulose-based SN injectable hydrogel with dualresponsiveness and self-healing properties for drug release and 3D encapsulation of
cells [77]. Hydrogels were formed through the dynamic covalent acylhydrazone
linkages between cellulose-graft-dithiodipropionate dihydrazide (CEC-TPH) and
dibenzaldehyde-functionalized poly(ethylene glycol) (PEG-DA) in the presence of
4-amino-dl-phenylalanine (4a-Phe) as a catalyst in aqueous media at room temperature (Fig. 32a). CEC-TPH installed redox responsiveness due to the disulfide
bridges, while the acylhydrazone linkages introduced tunable mechanical properties
and excellent self-healing capability. Visual self-healing experiments demonstrated
that hydrogels were healed for 6 h at 25
C (Fig. 32b). Furthermore, compressive
stress-strain tests were conducted on original and healed hydrogels to show recovery
of mechanical properties (Fig. 32c). The effect of healing time and 4a-Phe content on
Self-Healing Hydrogels Based on Reversible Covalent Linkages: A Survey of. . .
283
and did not self-heal under neutral environment which validates the fact that both
dynamic reactions involved in cross-linking were kinetically locked at neutral
pH. However, addition of catalytic amount of aniline in hydrogel precursors was
accelerating acylhydrazone dynamic reaction at neutral pH. Eventually, each of the
healed gels was found to be resistive toward stretching by a tweezer at the end of
healing process (Fig. 30b).
In 2015, Wei et al. synthesized a double-network (DN) self-healing hydrogel with
dynamic imine and acylhydrazone bonds coexisting in the cross-linked architecture
[75]. Hydrogel was prepared by mixing oxidized sodium alginate (OSA) solution
with N-carboxyethyl chitosan (CEC) and adipic acid dihydrazide (ADH) solution at
room temperature with different pH environments (PBS pH 7.0 or 6.0). Continuous
step strain measurements performed to assess the self-healing property of gels
suggested immediate recovery of their storage G
0 and loss moduli G
00 . In the same
year, Yu et al. reported a hyaluronic acid-based DN hydrogel cross-linked via the
Diels-Alder reaction and acylhydrazone bonds for tissue engineering applications
[76]. To fabricate the gels, two sets of HA derivatives were obtained: one
functionalized with furan and adipic dihydrazide (HA-furan-ADH) and the other
with furan and aldehyde (HA-furan-CHO) groups. Hydrogels were obtained by
mixing HA-furan-ADH and HA-furan-CHO in deionized water and cross-linked
via covalent acylhydrazone bond in several minutes. Thereafter, difunctionalized
PEG-maleimide (MAL-PEG-MAL) was added to the mixture to obtain DN through
the Diels-Alder cycloaddition reaction (Fig. 31a). To examine the mechanical
properties of self-healed hydrogels, compressive stress-strain tests were conducted
on original and healed hydrogels. Results demonstrated that both gels possessed
similar stress-strain curves (Fig. 31b). Standard DMA (dynamic mechanical analysis) test was used to compare the toughness of DN hydrogels with SN (only
acylhydrazone) and revealed that storage modulus G
0 of DN gel was significantly
higher than SN gel (Fig. 31c). Additionally, visual self-healing experiments were
carried out where samples were cut into two halves and put in contact for 3 h at
ambient temperature, and thus healed DN gel sample stood its own weight and
resisted pulling (Fig. 31d).
In 2017, Yang et al. reported a cellulose-based SN injectable hydrogel with dualresponsiveness and self-healing properties for drug release and 3D encapsulation of
cells [77]. Hydrogels were formed through the dynamic covalent acylhydrazone
linkages between cellulose-graft-dithiodipropionate dihydrazide (CEC-TPH) and
dibenzaldehyde-functionalized poly(ethylene glycol) (PEG-DA) in the presence of
4-amino-dl-phenylalanine (4a-Phe) as a catalyst in aqueous media at room temperature (Fig. 32a). CEC-TPH installed redox responsiveness due to the disulfide
bridges, while the acylhydrazone linkages introduced tunable mechanical properties
and excellent self-healing capability. Visual self-healing experiments demonstrated
that hydrogels were healed for 6 h at 25
C (Fig. 32b). Furthermore, compressive
stress-strain tests were conducted on original and healed hydrogels to show recovery
of mechanical properties (Fig. 32c). The effect of healing time and 4a-Phe content on
Self-Healing Hydrogels Based on Reversible Covalent Linkages: A Survey of. . .
283