Additionally, the disulfide bond scission can occur in the presence of a tripeptide,
namely, glutathione, found in elevated amounts in cancerous tissues and cells.
Cleavage of disulfide bond in the presence of thiol-containing molecules occurs
through a disulfide-thiol exchange reaction. The exchange reaction does not require
any catalyst, UV irradiation, or heat to be triggered. Due to aforementioned advantages, this chemistry has been utilized to yield self-healing hydrogels which may
possess a potential as redox-sensitive smart materials especially for drug delivery
and tissue engineering systems.
The concept of designing self-healing polymeric materials via the thiol-disulfide
redox reversible exchange reaction has been known for almost a decade.
Matyjaszewski and coworkers disclosed self-healing polymer films based on thioldisulfide exchange reaction [58]. Poly(n-butyl acrylate) multi-arm star polymers
were synthesized and further used as macroinitiators for chain extension by ATRP
of bis(2-methacryloyloxyethyl) disulfide to yield a disulfide cross-linked gel. This
disulfide cross-linked macroscopic gel was reduced to obtain thiol (SH)-bearing
polymers in solution. Thereafter, available SHs on the periphery of polymers were
oxidized by either I 2 or FeCl 3 . Disulfide cross-linked film was obtained upon
reformation of disulfide bonds by oxidation of thiol-functionalized polymers.
Scratches with different width and depth ranging from nanometers to micrometers
were formed on the surface of the film, and rapid self-healing behavior without
external intervention was reported, as deduced from analysis with atomic force
microscopy.
A few years later, in 2015, Waymouth and coworkers reported self-healing
hydrogels that contained disulfide linkages and could be formed under neutral
conditions [59]. They utilized 1,2-dithiolanes, i.e., five-membered cyclic disulfides,
to obtain reversible linkages. Hydrogels were synthesized from water-soluble ABA
triblock copolymers which contained a central poly(ethylene oxide) block and
terminal dithiolane blocks (p(TMCDT-PEG-TMCDT)). To obtain cross-linked network, p(TMCDT-PEG-TMCDT) copolymer was mixed with a dithiol, namely,
ODT, in water (Fig. 24a). Dynamic strain tests were carried out to demonstrate
self-healing using alternating strain between 1 and 800% for a 10 wt % hydrogel at
25
C. Strain-induced deformation was recovered immediately (<10 s) upon reducing strain to 1%, repeatedly (Fig. 24b). The frequency-dependent viscoelastic
behavior of the hydrogel was also investigated by rheological tests, and it was
compared with a hydrogel that was immersed in excess maleimide solution to cap
the free SH groups existing in gel construct irreversibly.
Designing disulfide containing hydrogels with self-healing property in acidic
condition will widen their area of application, and thus obtaining such systems is
desirable. To yield hydrogels that can self-heal under mildly acidic to alkaline
conditions, Zhang and coworkers reported an injectable, thermo-responsive hydrogel which was constructed by cross-linking thiol-functionalized F127 (HS-F127SH) and dithiolane-modified PEG (DT-PEG-DT) (Fig. 25a) in PBS (pH 7.38)
[60]. Hydrogels exhibited thermo-responsive gelation at body temperature (37
C)
and self-healing not only under alkaline conditions but also in neutral or even mildly
acidic conditions. Dynamic strain sweep measurements where strain was alternated
Self-Healing Hydrogels Based on Reversible Covalent Linkages: A Survey of. . .
275
namely, glutathione, found in elevated amounts in cancerous tissues and cells.
Cleavage of disulfide bond in the presence of thiol-containing molecules occurs
through a disulfide-thiol exchange reaction. The exchange reaction does not require
any catalyst, UV irradiation, or heat to be triggered. Due to aforementioned advantages, this chemistry has been utilized to yield self-healing hydrogels which may
possess a potential as redox-sensitive smart materials especially for drug delivery
and tissue engineering systems.
The concept of designing self-healing polymeric materials via the thiol-disulfide
redox reversible exchange reaction has been known for almost a decade.
Matyjaszewski and coworkers disclosed self-healing polymer films based on thioldisulfide exchange reaction [58]. Poly(n-butyl acrylate) multi-arm star polymers
were synthesized and further used as macroinitiators for chain extension by ATRP
of bis(2-methacryloyloxyethyl) disulfide to yield a disulfide cross-linked gel. This
disulfide cross-linked macroscopic gel was reduced to obtain thiol (SH)-bearing
polymers in solution. Thereafter, available SHs on the periphery of polymers were
oxidized by either I 2 or FeCl 3 . Disulfide cross-linked film was obtained upon
reformation of disulfide bonds by oxidation of thiol-functionalized polymers.
Scratches with different width and depth ranging from nanometers to micrometers
were formed on the surface of the film, and rapid self-healing behavior without
external intervention was reported, as deduced from analysis with atomic force
microscopy.
A few years later, in 2015, Waymouth and coworkers reported self-healing
hydrogels that contained disulfide linkages and could be formed under neutral
conditions [59]. They utilized 1,2-dithiolanes, i.e., five-membered cyclic disulfides,
to obtain reversible linkages. Hydrogels were synthesized from water-soluble ABA
triblock copolymers which contained a central poly(ethylene oxide) block and
terminal dithiolane blocks (p(TMCDT-PEG-TMCDT)). To obtain cross-linked network, p(TMCDT-PEG-TMCDT) copolymer was mixed with a dithiol, namely,
ODT, in water (Fig. 24a). Dynamic strain tests were carried out to demonstrate
self-healing using alternating strain between 1 and 800% for a 10 wt % hydrogel at
25
C. Strain-induced deformation was recovered immediately (<10 s) upon reducing strain to 1%, repeatedly (Fig. 24b). The frequency-dependent viscoelastic
behavior of the hydrogel was also investigated by rheological tests, and it was
compared with a hydrogel that was immersed in excess maleimide solution to cap
the free SH groups existing in gel construct irreversibly.
Designing disulfide containing hydrogels with self-healing property in acidic
condition will widen their area of application, and thus obtaining such systems is
desirable. To yield hydrogels that can self-heal under mildly acidic to alkaline
conditions, Zhang and coworkers reported an injectable, thermo-responsive hydrogel which was constructed by cross-linking thiol-functionalized F127 (HS-F127SH) and dithiolane-modified PEG (DT-PEG-DT) (Fig. 25a) in PBS (pH 7.38)
[60]. Hydrogels exhibited thermo-responsive gelation at body temperature (37
C)
and self-healing not only under alkaline conditions but also in neutral or even mildly
acidic conditions. Dynamic strain sweep measurements where strain was alternated
Self-Healing Hydrogels Based on Reversible Covalent Linkages: A Survey of. . .
275