CNCs (CNC-NH 2 ) were used to tune the mechanical properties of the
polysaccharide hydrogel. The CNC-reinforced composite hydrogel provides both
physical and chemical cross-linking at the same system. By one-step mixing of
CNC-NH 2 , HPCS, and CAA, enamine bond formation and the consequent gelation
occurred rapidly at room temperature. The dynamic equilibrium of the enamine
bonds in the cross-linked network endowed the polysaccharide hydrogel with selfhealing abilities and pH-responsive properties.
3.1.2 Acylhydrazone Bonds
Acylhydrazone bonds, formed by the condensation reaction of aldehydes with
hydrazides, are a closely related bond type with Schiff bases but are much more
stable with reversibility under mild conditions. Thus, the acylhydrazone bonds have
been utilized to construct the dynamic hydrogels with diverse functions, such as selfhealing ability, stimuli responsiveness, and robust mechanical property [127–
132]. A straightforward one-pot oxidation can surface functionalized CNCs with
aldehyde groups by sodium periodate. Cranston’s group reported all-polysaccharide
hydrogel system based on the acylhydrazone cross-links [133–135]. By mixing the
aldehyde-functionalized CNCs (CHO-CNCs) with other aldehyde-functionalized
polymers and coextruding the mixture with hydrazide-modified polymers,
hydrazone bond formation and gelation occur rapidly as the hydrogel components
came into contact. For example, injectable hydrogels of dextran and carboxymethyl
cellulose were reinforced with CNCs acting as simple fillers (unmodified CNCs) or
as chemical cross-linkers (aldehyde-functionalized CNCs) [134]. No additional
chemicals, changes in temperature, or processing was required for gelation, and
hydrazine cross-links were formed when the adipic acid dihydrazide-modified
carboxymethyl cellulose (CMC-NHNH 2 ), aldehyde-modified dextran (dextranCHO), and CHO-CNCs solutions came into contact under normal physiological
conditions. However, the dynamic acylhydrazone bonds can only proceed in a
slightly acidic environment (pH ¼ 4.0–6.0), and the reaction efficiency dropped
off sharply at pH outside these ranges. Indeed, the dynamic acylhydrazone bonds
tend to be kinetically locked under a neutral condition, so the self-healing performance of the hydrogels was significantly impaired and even disappeared.
In order to address the demand for the biocompatible, strong, and efficient selfhealing hydrogels based on acylhydrazone bonds in the practical biomedical applications, Yang et al. [126] presented new cellulose-based self-healing hydrogels with
dual-responsive and good mechanical properties constructed through the dynamic
covalent acylhydrazone linkages (Fig. 6). The carboxyethyl cellulose-graftdithiodipropionate dihydrazide (CEC-TPH) and dibenzaldehyde-terminated poly
(ethylene glycol) (PEG-DA) were initially synthesized, and then the hydrogels
could be generated from their mixed solutions under 4-amino-DL-phenylalanine
(4a-Phe) catalysis (Fig. 6a). The resulted hydrogels exhibited excellent self-healing
ability with a high healing efficiency (%96%) and good mechanical properties. The
self-healing abilities of the obtained hydrogels were evaluated by direct visual
Dynamics in Cellulose-Based Hydrogels with Reversible Cross-Links
333
polysaccharide hydrogel. The CNC-reinforced composite hydrogel provides both
physical and chemical cross-linking at the same system. By one-step mixing of
CNC-NH 2 , HPCS, and CAA, enamine bond formation and the consequent gelation
occurred rapidly at room temperature. The dynamic equilibrium of the enamine
bonds in the cross-linked network endowed the polysaccharide hydrogel with selfhealing abilities and pH-responsive properties.
3.1.2 Acylhydrazone Bonds
Acylhydrazone bonds, formed by the condensation reaction of aldehydes with
hydrazides, are a closely related bond type with Schiff bases but are much more
stable with reversibility under mild conditions. Thus, the acylhydrazone bonds have
been utilized to construct the dynamic hydrogels with diverse functions, such as selfhealing ability, stimuli responsiveness, and robust mechanical property [127–
132]. A straightforward one-pot oxidation can surface functionalized CNCs with
aldehyde groups by sodium periodate. Cranston’s group reported all-polysaccharide
hydrogel system based on the acylhydrazone cross-links [133–135]. By mixing the
aldehyde-functionalized CNCs (CHO-CNCs) with other aldehyde-functionalized
polymers and coextruding the mixture with hydrazide-modified polymers,
hydrazone bond formation and gelation occur rapidly as the hydrogel components
came into contact. For example, injectable hydrogels of dextran and carboxymethyl
cellulose were reinforced with CNCs acting as simple fillers (unmodified CNCs) or
as chemical cross-linkers (aldehyde-functionalized CNCs) [134]. No additional
chemicals, changes in temperature, or processing was required for gelation, and
hydrazine cross-links were formed when the adipic acid dihydrazide-modified
carboxymethyl cellulose (CMC-NHNH 2 ), aldehyde-modified dextran (dextranCHO), and CHO-CNCs solutions came into contact under normal physiological
conditions. However, the dynamic acylhydrazone bonds can only proceed in a
slightly acidic environment (pH ¼ 4.0–6.0), and the reaction efficiency dropped
off sharply at pH outside these ranges. Indeed, the dynamic acylhydrazone bonds
tend to be kinetically locked under a neutral condition, so the self-healing performance of the hydrogels was significantly impaired and even disappeared.
In order to address the demand for the biocompatible, strong, and efficient selfhealing hydrogels based on acylhydrazone bonds in the practical biomedical applications, Yang et al. [126] presented new cellulose-based self-healing hydrogels with
dual-responsive and good mechanical properties constructed through the dynamic
covalent acylhydrazone linkages (Fig. 6). The carboxyethyl cellulose-graftdithiodipropionate dihydrazide (CEC-TPH) and dibenzaldehyde-terminated poly
(ethylene glycol) (PEG-DA) were initially synthesized, and then the hydrogels
could be generated from their mixed solutions under 4-amino-DL-phenylalanine
(4a-Phe) catalysis (Fig. 6a). The resulted hydrogels exhibited excellent self-healing
ability with a high healing efficiency (%96%) and good mechanical properties. The
self-healing abilities of the obtained hydrogels were evaluated by direct visual
Dynamics in Cellulose-Based Hydrogels with Reversible Cross-Links
333