disk and allowed to heal for 12 h in humid atmosphere. Resulted hydrogel demonstrated almost the same G
0 value as the in situ formed hydrogel, thus proving good
self-healing ability. Macroscopic self-healing of two cut pieces is illustrated in
Fig. 6b where two pieces of Dex-aT3/CECS hydrogel healed immediately after
they were put in contact at room temperature. Several cell types including myoblast
cell are encapsulated and released from the hydrogel with good viability and
proliferation ability. This novel biocompatible self-healing hydrogel has a great
potential as a cell delivery carrier for skeletal muscle or tissue repair.
In 2017, Guo and coworkers used N-carboxyethyl chitosan (CEC) and PEG-DA
to obtain self-healing hydrogel for local delivery of chemotherapeutic agent doxorubicin (DOX). CEC was synthesized by a green method in this work using water as
a solvent. Hydrogels were obtained by mixing polymer solutions prepared in
deionized (DI) water at 37
C, and rapid gel formation (within ca. 60 s) was recorded
by using vial tilting method. Self-healing assessment was done by visual and
quantitative experiments. In visual experiments, when four pieces of stained
hydrogels were incubated at 25
C for 3 h, boundary disappearance was observed.
In quantitative experiments, alternate strain test was carried out between 1 and 300%
strain values for three cycles. Under high strain (300%), storage modulus (G
0 ) of
hydrogel decreased from 11 to 1.05 kPa showing strain-induced network deformation and unloading strain on hydrogel (1%) enabled recovery of G
0 back to its initial
value within 100 s [19].
Self-healing hydrogels containing a protein-based component were reported by
Hsu and coworkers in 2017. They synthesized a chitosan-fibrin (CF)-based hydrogel
in water and compared the self-healing property with fibrin and classical glyco
chitosan (CS)-based gels with similar physical properties. The CF and CS hydrogel
systems were optimized to obtain suitable stiffness (1.2 kPa) for blood capillary
formation, and fibrin gel was used as a positive control. Fibrinogen gels were
obtained in the presence of thrombin, which converts it to a fibrin network. To
demonstrate macroscopic self-healing properties of resulted gels, the disappearance
of a punctured hole in hydrogels was investigated. Fibrin gel did not self-heal, as
expected, but the CF gel showed faster healing than the traditional CS hydrogel
system (Fig. 7a). Aditionally, rheological tests were carried out, which indicated that
the breaking strain of CF gel was higher than CS gel, yet, both CS and CF hydrogels
showed quick recovery in continuous step strain tests where strain was alternated
between 1 and 150% (Fig. 7b) [20].
The utility of such Schiff base-based hydrogels was expanded by a recent study
by Zhao, Sun, and coworkers. They designed an injectable self-healing hydrogel as
microwave ablation therapy agent by simply mixing GCS and difunctionalized
DF-PEG in saline, at room temperature. The ionic hydrogel produced hightemperature hyperthermia upon a low power density microwave (2.0 W,
2.45 GHz) exposure because of the ions that are fixed through saline. Self-healing
property of hydrogel is demonstrated by using a periodic step change of oscillatory
strain between 300 and 1%. G
0 of damaged hydrogel returned back to its initial value
quickly upon reducing strain to 1% [21]. Another example utilizing similar combination was reported by Hsieh and coworkers in 2018, who designed a self-healing
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R. Kilic and A. Sanyal
0 value as the in situ formed hydrogel, thus proving good
self-healing ability. Macroscopic self-healing of two cut pieces is illustrated in
Fig. 6b where two pieces of Dex-aT3/CECS hydrogel healed immediately after
they were put in contact at room temperature. Several cell types including myoblast
cell are encapsulated and released from the hydrogel with good viability and
proliferation ability. This novel biocompatible self-healing hydrogel has a great
potential as a cell delivery carrier for skeletal muscle or tissue repair.
In 2017, Guo and coworkers used N-carboxyethyl chitosan (CEC) and PEG-DA
to obtain self-healing hydrogel for local delivery of chemotherapeutic agent doxorubicin (DOX). CEC was synthesized by a green method in this work using water as
a solvent. Hydrogels were obtained by mixing polymer solutions prepared in
deionized (DI) water at 37
C, and rapid gel formation (within ca. 60 s) was recorded
by using vial tilting method. Self-healing assessment was done by visual and
quantitative experiments. In visual experiments, when four pieces of stained
hydrogels were incubated at 25
C for 3 h, boundary disappearance was observed.
In quantitative experiments, alternate strain test was carried out between 1 and 300%
strain values for three cycles. Under high strain (300%), storage modulus (G
0 ) of
hydrogel decreased from 11 to 1.05 kPa showing strain-induced network deformation and unloading strain on hydrogel (1%) enabled recovery of G
0 back to its initial
value within 100 s [19].
Self-healing hydrogels containing a protein-based component were reported by
Hsu and coworkers in 2017. They synthesized a chitosan-fibrin (CF)-based hydrogel
in water and compared the self-healing property with fibrin and classical glyco
chitosan (CS)-based gels with similar physical properties. The CF and CS hydrogel
systems were optimized to obtain suitable stiffness (1.2 kPa) for blood capillary
formation, and fibrin gel was used as a positive control. Fibrinogen gels were
obtained in the presence of thrombin, which converts it to a fibrin network. To
demonstrate macroscopic self-healing properties of resulted gels, the disappearance
of a punctured hole in hydrogels was investigated. Fibrin gel did not self-heal, as
expected, but the CF gel showed faster healing than the traditional CS hydrogel
system (Fig. 7a). Aditionally, rheological tests were carried out, which indicated that
the breaking strain of CF gel was higher than CS gel, yet, both CS and CF hydrogels
showed quick recovery in continuous step strain tests where strain was alternated
between 1 and 150% (Fig. 7b) [20].
The utility of such Schiff base-based hydrogels was expanded by a recent study
by Zhao, Sun, and coworkers. They designed an injectable self-healing hydrogel as
microwave ablation therapy agent by simply mixing GCS and difunctionalized
DF-PEG in saline, at room temperature. The ionic hydrogel produced hightemperature hyperthermia upon a low power density microwave (2.0 W,
2.45 GHz) exposure because of the ions that are fixed through saline. Self-healing
property of hydrogel is demonstrated by using a periodic step change of oscillatory
strain between 300 and 1%. G
0 of damaged hydrogel returned back to its initial value
quickly upon reducing strain to 1% [21]. Another example utilizing similar combination was reported by Hsieh and coworkers in 2018, who designed a self-healing
252
R. Kilic and A. Sanyal