Advanced Materials - 2016 - Taylor - Self Healing Hydrogels

15214095, 2016, 41, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/adma.201601613 by Universidad del Bio Bio, Wiley Online Library on [15/01/2023].
See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
www.advmat.de
www.MaterialsViews.com
REVIEW
Self-Healing Hydrogels
Danielle Lynne Taylor and Marc in het Panhuis*
structure after rheological deforma-

Over the past few years, there has been a great deal of interest in the devel- tion.[2,3] Development of materials
opment of hydrogel materials with tunable structural, mechanical, and that have the ability to self-heal from
rheological properties, which exhibit rapid and autonomous self-healing and an event of damage has the potential
to prolong not only the life-time of a
self-recovery for utilization in a broad range of applications, from soft robotics
material but also restore and/or retain
to tissue engineering. However, self-healing hydrogels generally either pos- its original properties. Furthermore, it
sess mechanically robust or rapid self-healing properties but not both. Hence, can lead to increases in the durability,
the development of a mechanically robust hydrogel material with autono- reliability and, in certain applications,
mous self-healing on the time scale of seconds is yet to be fully realized. the safety of the material by avoiding
Here, the current advances in the development of autonomous self-healing failures caused by the accumulation of
cracks (or breaks). Even with the blue-
hydrogels are reviewed. Specifically, methods to test self-healing efficiencies prints provided by nature, the design
and recoveries, mechanisms of autonomous self-healing, and mechanically and development of self-healing mecha-
robust hydrogels are presented. The trends indicate that hydrogels that self- nisms via synthetic pathways are often
heal better also achieve self-healing faster, as compared to gels that only par- complex and difficult to control.[4–6]
tially self-heal. Recommendations to guide future development of self-healing In contrast to nature, synthetic mate-
rials, such as hydrogels, usually fail
hydrogels are offered and the potential relevance of self-healing hydrogels
catastrophically and without repair.
to the exciting research areas of 3D/4D printing, soft robotics, and assisted Self-healing and self-recovery (SELF)
health technologies is highlighted. mechanisms inspired or mimicked by
those encountered in natural systems
are being incorporated into synthe-
1. Introduction sized polymeric materials (hydrogels).[5] For instance, hydrogels
laden with healing agents or synthetic three-dimensional vas-
Autonomous self-healing is defined as the property that ena- cular networks have been developed to mimic skin and its self-
bles a material to intrinsically and automatically heal damages, healing functionality.[7,8] Another example is the blue mussel’s
restoring itself to normality. Autonomous self-healing usually secretions that have inspired the development of smart polymer
occurs in as-prepared materials (with a predefined set of con- hydrogels that utilize their responsivity to pH to self-heal.[9–11]
ditions) without the intervention of an external stimulus to Hydrogels are soft materials that possess 3D network struc-
promote the onset or magnitude of self-healing. Self-healing, ture with tuneable physical and chemical properties. The uti-
self-repair, and self-recovery are used synonymously, and refer lization of hydrogels is widespread across many areas with
to a material’s ability to self-mend damage and regain its asso- particular promise in biomedical fields.[12] Hydrogels are
ciated mechanical properties. Self-healing requires rebonding prominently used in many commercialized products such as
of a material to its original shape/condition, e.g., cutting a gel in wound dressings, contact lenses, and hygiene products.[13]
in half and then allowing it to bond back together again.[1] In The pre-gel fluidity of a hydrogel enables the filling of irregular
contrast, self-recovery refers to mending of internal damage cavities and shapes without the need for pre-shape forming
and tests a material’s viscoelastic properties, e.g., molecular processing. The water-retention abilities and network struc-
diffusion of ionic crosslinks to regain the 3D polymer-network ture can be similar to those of the extracellular matrix, making
hydrogels ideal for use as scaffolds in tissue engineering appli-
cations.[14–19] Hydrogels are being investigated for their use in
drug delivery as gel solutions can be loaded with biologically
D. L. Taylor, Prof. M. in het Panhuis active compounds, such as drugs and antibodies.[20–22] The
Soft Materials Group, School of Chemistry hydrogel carrier acts as a protection barrier from degradation
University of Wollongong
Wollongong, NSW 2522, Australia (e.g., enzymatic degradation) and controls the release of the
E-mail: panhuis@uow.edu.au loaded compounds.[20,23] Hydrogels hold great promise in the
Prof. M. in het Panhuis development of artificial implants (e.g., artificial meniscus).[24]
ARC Centre of Excellence for Electromaterials Science Traditionally, materials have been developed focussing on
AIIM Facility damage prevention in the form of tough wear-resistant mate-
University of Wollongong
Wollongong, NSW 2522, Australia
rials and not the ability to mend. Repairing materials at failure
is usually achieved via the addition of fillers or adhesives that
DOI: 10.1002/adma.201601613 do not retain the material’s original properties. Often SELF
9060 wileyonlinelibrary.com © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Adv. Mater. 2016, 28, 9060–9093
15214095, 2016, 41, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/adma.201601613 by Universidad del Bio Bio, Wiley Online Library on [15/01/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
www.advmat.de
REVIEW
systems involve the addition of healing agents to repair the
damage.[25] Breaks and cracks usually occur well before notice- Danielle Taylor is a Ph.D. can-
able damage is detected at the point of failure. Polymeric didate in the Soft Materials
materials currently in use are ineffective at preventing (or Group at the University
even delaying) the advancement of mechanical damage. How- of Wollongong (UOW) in
ever, the development of hydrogels that are able to respond to Australia. She has several
damage and self-heal (and/or self-recover) intrinsically have years experiences in polymer
emerged as a viable solution. For intrinsic SELF in hydrogels, research. Currently she is
the SELF capabilities are chemically or compositionally incor- working on hydrogels that
porated directly into the polymeric architectures via the incor- can self-heal and self-recover
poration of reversible bonds (crosslinks/reactions). autonomously and are
Hydrogel systems that are to possess autonomous SELF mechanically robust. These
capabilities must adhere to specified design criteria. Ideally the self-healing and self-recov-
self-healing hydrogel should be produced from inexpensive and ering hydrogels can be 3D-printed and are intended for
nontoxic/nonhazardous materials and techniques, and should application in soft robotics.
not degrade prematurely in respect to the application. Addition-
ally, autonomously self-healing hydrogels must: i) respond to Marc in het Panhuis is
damage autonomously (without external stimuli), rapidly and a Professor of Materials
repeatedly, ii) respond to damage (self-heal) from the micro- to Science in the School of
macroscale, iii) possess mechanical, rheological and other prop- Chemistry, the Associate
erties (e.g., biocompatibility) appropriate for the intended appli- Dean (International) for
cation, and iv) retain their original mechanical and rheological the Faculty of Science,
properties after self-healing.[4] Research into SELF hydrogels Medicine and Health, and
involves two main approaches; dynamic covalent reactions Chief Investigator in the
(chemical crosslinking) and noncovalent reactions (physical Australian Research Council
crosslinking).[5] Covalent reactions employed in hydrogel self- Center of Excellence for
healing often require the reapplication of the conditions used Electromaterials Science at
for polymerization or the application of an external stimulus, the University of Wollongong
e.g., pH,[10,26] alternating current (AC),[27] or UV light.[28–31] (UOW, Australia). His research laboratories are located in
There has been extensive research conducted on hydrogels the Australian Institute for Innovative Materials at UOW’s
and other polymeric materials that self-heal in response to a Innovation Campus and his activities are focused on tough
stimulus, and a number of reviews have been published sum- hydrogels, their mechanical (including recoverability) and
marizing this work.[1,6,32–38] Hydrogels that utilize dynamic electrical characterization, interactions with living cells,
covalent reactions that require no external intervention are and their processing using Additive Manufacturing (3D/4D
less common.[39,40] In the case of autonomous SELF hydrogels, printing) for applications in water treatment, tissue engi-
noncovalent interactions are generally utilized, separately or in neering, edible electronics, and soft robotics.
combination, such as ionic bonding,[41–43] hydrogen-bonding,[44]
supramolecular interactions,[45] hydrophobic bonding,[46] and
molecular diffusion and chain entanglement.[47]
Conventional hydrogels are considered to be weak and
brittle (low toughness) with fracture energies of <10 J m−2.[48] are capable of large deformations have been developed, incor-
Good mechanical properties are those comparable to that of porating multiple crosslinking mechanisms (not all are neces-
cartilage.[49] Articular cartilage is a proteoglycan gel matrix sarily used in the SELF mechanisms), such as those in (nano)
reinforced with collagen fibers and holds a crucial role in load composites and hybrid and interpenetrating polymer net-
bearing and load distribution of the knee.[12,49] Articular carti- works (IPN).[48] IPNs consist of two or more intertwined net-
lage exhibits high toughness (fracture energy of ≈1000 J m−2)[50] works absent of crosslinks between networks.[62,63] However, in
and high tensile strengths of up to 30 MPa.[12] The stretch- some instances the incorporation of a robust second network
ability of articular cartilage is limited with tensile elongation has been shown to limit SELF capabilities. For example, self-
ratios of a maximum of 140%.[51] The lack of mechanical tough- recovering IPN hydrogels that incorporate a second network of
ness exhibited by conventional hydrogels is analogous to that non-reversible chemical crosslinks do not reach 100% healing
of SELF hydrogels. Additionally SELF hydrogels exhibit poor recovery.[2,3] Once the bonds of the covalent network are broken
mechanical properties, a consequence of the weaker and revers- they cannot be re-formed and the damage is irreversible.[62] The
ible nature of the noncovalent interactions compared to that development of tough and rapid autonomous SELF hydrogels
of covalent bonding. Approaches for designing tough SELF has progressed but they are yet to be fully realized.
hydrogels are centerd on the efficient dissipation of mechanical Here, we take a detailed look at current polymeric hydrogel sys-
energy induced around the damaged area via the breakage of tems that possess autonomous SELF properties. We investigate
sacrificial bonds.[52–58] In this instance sacrificial bonds are pur- SELF hydrogels with a focus on methods to test for the efficien-
posefully included in the hydrogel networks and are designed cies of self-healing and recovery, and mechanisms of autonomous
to prevent backbone cleavage.[48,55,59–61] SELF hydrogels that SELF. This is followed by an explanation of the development of
Adv. Mater. 2016, 28, 9060–9093 © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim wileyonlinelibrary.com 9061
www.advmat.de
REVIEW
hydrogels that possess both SELF and robust mechanical prop- tests and used to quantify self-healing efficiencies. The healing
erties. We summarize the current work on autonomous SELF efficiency can be expressed as a ratio (or percentage) of a meas-
hydrogels, and recommend a number of future directions. In ured property of the healed and virgin hydrogels.[46]
particular, we highlight the potential use of SELF hydrogels com- Uniaxial elongation measurements have been performed on
bined with 3D/4D printing, and in application areas such as soft cylindrical and dog-bone-/dumbbell-shaped hydrogels of var-
robotic actuators and assisted health technologies. ying sizes that have been cut and the pieces pressed together
for a specified heal time.[7,46,52,54] Elongation at break meas-
ures the percentage increase in length of a stretched hydrogel
2. Testing for Autonomous SELF of Hydrogels before it breaks. The elongation ratio of the pristine (λb,0) and
healed (λb) hydrogels were used to determine the efficiency of
Autonomous SELF is used to describe systems that self-heal self-healing:[7,40,46,65]
and/or self-recover without the application of a stimulus out-
side of a predefined set of conditions. This predefined set of ⎛ λ ⎞
conditions is usually that of the “as-prepared hydrogels” or the ε H = ⎜ b ⎟ × 100 (1)
⎝ λ b,0 ⎠
conditions set by the practical application of the hydrogels.
It is important to define the set of environmental conditions For example, poly(N,N-dimethylacrylamide) was shown to
as working outside of these delves into the field of stimuli- self-heal after 10 min at 24 °C: a hydrogel sample was cut in
responsive hydrogels; for example, the temperature at which two (one dyed pink for clarity) and the two halves were placed
the tests are conducted can greatly affect SELF properties. It is back together.[65] After 10 min the hydrogel was stretched
conventional to assess a hydrogel’s self-healing ability by obser- without breaking to demonstrate the autonomous self-healing
vation, i.e., macroscopically by breaking it in half, placing the (Figure 1a). Tensile measurements (stress–strain curves) of
two pieces together, and visually noting changes occurring at virgin and self-healed samples (healed for various healing
the interface.[39,43] Testing the hydrogel’s ability to support its times) of the poly(N,N-dimethylacrylamide) hydrogel were con-
own weight after healing without breaking is another common ducted (Figure 1b). After 10 min, the healed hydrogel exhibited
test.[39,64] A comparative analysis of the self-healing abilities of a tensile fracture stress of 15 kPa, whereas 25 kPa was exhibited
different hydrogels is often difficult. Several different methods by the virgin hydrogel. Expressing the fracture stress of the
of quantitatively determining the self-healing are employed. For healed hydrogel as a percentage to that of the virgin hydrogel
example, bulk damage is assessed using tension or compression (15/25 × 100), a healing efficiency of 60% is obtained. If the
Figure 1. Self-healing test and efficiencies: a) Photographs of two poly(N,N-dimethylacrylamide) self-healing hydrogels. One of the samples was
colored with a dye for clarity. After cutting into two pieces and pressing the fractured surfaces together for 10 min at 24 °C, the hydrogel heals to form
a single hydrogel. b) Tensile measurements of the virgin hydrogel (uncut) and the healed hydrogel (hydrogel cut and halves placed back together) that
have healed for 2, 5, 10, 15, and 20 min. Reproduced with permission.[65] Copyright 2014, Elsevier. c) Self-recovery test: alternate step-strain relaxation
experiment at 25 °C. Large strain (1000%) inverted the values of G′ (squares) and G″ (circles), indicating breakage of crosslinks and conversion to
solution state. G′ was recovered under a small strain (10%) within 30 s. Reproduced with permission.[68] Copyright 2014, American Chemical Society.
www.advmat.de
REVIEW
healing time is increased to 20 min, a healing efficiency of number of linkages and strength (type) of moieties utilized in
100% is obtained.[65] It has been shown that bulk ruptures the linkages determine the degree of SELF ability, the stability
and larger samples require larger healing times compared to of the hydrogel formation, and the mechanical properties of
microscopic fractures and smaller samples, while both the time the hydrogel. This is important when designing hydrogels with
allowed for repair to occur and different geometries (e.g., cyl- regard to a particular application. For example, hydrogels com-
inder vs dumbbell) can affect the efficiencies obtained. The type posed of physical crosslinks that employ weaker interactions
of efficiency testing may also be limited by the softness of the (such as hydrogen bonding) are inherently weaker compared to
gels. For example, mechanically weak hydrogels may not have covalently crosslinked networks.[69,71]
the structural stability to withstand clamping for tensile testing.
Instead, their healing efficiencies are determined using com-
pression testing.[45,66,67] 3.1. Dynamic Covalent Bonding
Self-recovery is used to quantify a material’s ability to recover
from internal damage and the subsequent restoration of Dynamic covalent crosslinks are permanent bonds that can
mechanical viscoelastic properties. Mechanical testing of self- break and re-form. Depending on the conditions, these bonds
recovery generally involves cyclic loading/unloading in tension, can be as reversible as non-covalent physical bonds or per-
compression or shear. Strain-relaxation experiments (or alter- manent like conventional covalent bonds. For example, a
nate step strain measurements) involve exposing the hydrogels self-healing network that exploits two dynamic covalent mecha-
to a constant deformation (strain) in a stepwise manner over nisms, acylhydrazone and disulfide bonds, was developed by
a period of time (Figure 1c). These tests reveal the material’s Deng et al.[72] In this poly(ethylene oxide) (PEO)-based hydrogel,
viscoelastic response to damage and subsequent reversibility acylhydrazone exchange reactions occur at acidic pH, while
of internal crosslinks. A decrease of the storage modulus with disulfide exchange reactions occur at basic pH. The hydrogel
applied strain is an indication that the applied force is sufficient exhibited autonomous self-healing at room temperature (RT)
in overcoming the interactions associated with the crosslinks of (20 °C) over a large pH range by intrinsically selecting between
the network. Once the high strain is removed, self-recovering the two dynamic mechanisms. However, self-healing did not
hydrogels exhibit recovery of their storage/loss moduli, and this work at neutral pH as the covalent bonds were not dynamic.[72]
time-course experiment can be used to reveal the lifetime of the Other examples include hydrogels consisting of triblock
reversible interactions.[68] A similar experiment tracking the vis- (ABA) copolymers, with a central poly(ethylene oxide) block
cosity with changes in shear rate has also been reported.[69] and terminal dithiolane blocks. The SELF behavior was a result
The type of crosslinking utilized in hydrogel formation has of the reversible ring opening of the pendant 1,2-dithiolanes
been shown to limit self-recovery. Physically crosslinked net- caused by the disulfide exchange between the 1,2-dithiolanes
works generally exhibit 100% self-recovery.[70] However, the self- and dithiols. The self-healing nature enabled the hydrogel to
recovery of IPNs with chemical and physical crosslinks gener- be injected through a syringe. The hydrogel exhibited imme-
ally does not reach 100% due to the irreversible nature of the diate and complete self-recovery of storage and loss moduli
covalent linkages of one network. Hysteresis (the amount of after severe step-strain deformations (γ = 1 or 800%) at
energy dissipated during a loading/unloading cycle), calculated 25 °C.[73] SELF hydrogel coatings were developed by the photo-
from compressive and tensile stress–strain measurements, is polymerization of monomers poly(ethylene glycol) methyl
used to determine a hydrogel’s ability to recover from deforma- ether methacrylate (PEGMA), N-hydroxyethyl acrylamide
tion. The first cycle reveals the limit of recovery imposed on (HEAA), and 2-(methacryloyloxy)-ethyl trimethylammonium
the IPN by damage to the irreversible covalent network. Sub- chloride (META), and a disulfide-containing crosslinker bis(2-
sequent cycles can reach 100% recovery compared to the initial methacryloyl)-oxyethyl disulfide (BMOD). Hydrogel-coated
loading cycle (dependant of healing time). This is an indication stainless steel was scratched (>10 µm) by the probe of a step
of recovery, achieved as a result of the reversible crosslinks of profiler and self-healing observed via an optical microscope to
the physical second network.[3] However, self-recovery is gener- occur in 30–60 min at RT (20 °C).[74] When samples were cut
ally on the time-scale of minutes to hours, due to the nature of by razors to form microscopic cuts (≈10 µm), self-recovery was
the reversible crosslinks. For instance, an ionically crosslinked observed by atomic force microscopy (AFM) to occur within
gellan gum and covalently genipin-crosslinked gelatin IPN was 72 h at RT (20 °C). In both instances, the recovery and healing
able to recover 82 ± 7% hysteresis after resting in simulated were attributed to the dynamic interactions of the disulfide
body fluid for 5 h after the first loading cycle at 21 °C.[2] IPNs exchange. These hydrogel coatings also exhibited antifouling
composed of ionically crosslinked gellan gum and covalently and antibacterial properties.[74] SELF in neutral conditions
crosslinked poly(acrylamide) were able to recover 53 ± 4% hys- was achieved using an N-carboxylethyl chitosan–oxidized
teresis after 80 min rest between cycles at 21 °C.[3] sodium alginate–adipic acid dihydrazide (CEC-l-OSA-l-ADH)
hydrogel,[66] which contained reversible acylhydrazone bonds
formed between the oxidized sodium alginate (OSA) and the
3. Mechanisms of SELF adipic acid dihydrazide, as well as reversible imine bonds
between the OSA and the N-carboxylethyl chitosan. It was
The mechanisms of SELF are reliant on the reversibility of shown that, at neutral pH, imine bonding is the predominant
the crosslinks. Dynamic covalent, hydrogen bonding, ionic, self-healing mechanism. Self-healing efficiencies (beam-shaped
supramolecular host–guest, and hydrophobic interactions have compression) of up to 90 ± 2.7% were achieved after 48 h of
been incorporated into SELF polymeric hydrogel networks. The healing at 25 °C. Self-recovery of the storage and loss moduli
www.advmat.de
REVIEW
Figure 2. The injectability of the self-healing CEC-l-OSA-l-ADH hydrogel. a) Two disk-shaped hydrogels (one stained with rhodamine B and the other
stained with methylene blue) were separately injected into a beaker and compacted together (b,c). d) The hydrogel disk autonomously self-healed
after 6 h at 25 °C and could stand. e,f) After immersion in PBS (pH 7.0) for 3 h, the healed hydrogel disk could maintain its integrity. Reproduced with
permission.[66] Copyright 2015, Wiley-VCH.
was achieved immediately from alternate strain-deformation reversible and no self-healing was observed. The reversibility of
measurements (γ = 1, 80, 300, or 800%). SELF was demon- the imine linkages was not limited to freshly cut or damaged
strated by injecting solid samples into a beaker. The fragmented surfaces, with four separately prepared hydrogels becoming
pieces were compacted together and left to re-form one solid unified with no visible interfaces when stretched after 3 h
structure after 6 h at 25 °C (Figure 2).[66] (Figure 3h–k). Complete recovery of the mechanical properties
Several research groups have utilized the reversibility of was also observed from step-strain deformation measurements
dynamic Schiff base (imine) linkages to achieve SELF. Telech- (γ = 1 or 200%) at 25 °C.[78] A reversible imine linkage was also
elic dibenzaldehyde-terminated poly(ethylene glycol) (PEG) was utilized in an injectable chondroitin sulfate multiple aldehyde
synthesized by esterification of hydroxyl-terminated PEG with and N-succinyl-chitosan self-healing hydrogel for cell encapsu-
4-formylbenzoic acid.[75] When the functionalized PEG is com- lation. Self-healing of a hydrogel cut in two halves and placed
bined with a solution of chitosan, a hydrogel is formed that self- back together was achieved in 2 h at RT (20 °C) with reinforce-
heals in 2 h at RT (20 °C). Recovery of mechanical properties ment via hydrogen bonding and chain entanglement.[79]
was observed from alternate step-strain-deformation measure- The dynamic covalent transesterification reaction of boronic
ments within 100 s (γ = 200 or 200%) at 37 °C.[75] Replacing acid with diols has been utilized as an autonomous SELF
the chitosan with glycol chitosan resulted in better solubility mechanism.[39] 2-Acrylamidophenylboronic acid was copo-
under physiological conditions (Figure 3a). These hydrogels lymerized with N,N′-dimethylacrylamide. The copolymer
exhibited autonomous self-healing in 12 h at RT (20 °C) and was then crosslinked with either diol-containing poly(vinyl
act as a promising vehicle for the encapsulation of neural stem alcohol) or the catechol-functionalized copolymer of N,N′-
cells for repairing deficits of the central nervous system. The dimethylacrylamide and dopamine acrylamide. Intermolecular
self-recovery of these hydrogels was demonstrated by con- coordination, via the favorable tetrahedral geometry of boron
tinuous step-strain (1% strain → 300% strain → 1% strain) atoms, was shown to stabilize the crosslinks across a large pH
measurements at 37 °C (Figure 3b).[76] After injection through and promote boron ester formation. The hydrogels exhibited
a needle, a homogeneous hydrogel could be recovered, and its complete self-healing after 1 h (at acidic to neutral pH) at RT
use as an injectable cell-therapy carrier was demonstrated.[76,77] (20 °C). The catechol-functionalized copolymer hydrogel’s self-
Schiff base reactions (reversible imine linkages) were utilized healing capabilities are limited to within 48 h after hydrogel for-
as the SELF mechanism of an acrylamide-modified chitin and mation. This is a result of the oxidation of the catechol groups
oxidized alginate self-crosslinking hydrogel.[78] Sliced and reat- and subsequent formation of permanent and nonreversible
tached hydrogels were shown to visually self-heal and regain quinone crosslinks. These gels displayed rheological properties
conformity of shape after 3 h at neutral and basic pH at RT consistent with reversible crosslinks with frequency-dependent
(20 °C) (Figure 3c–g). At pH 5, the imine linkages were not moduli, with G′ > G″ at high frequencies. Complete recovery
www.advmat.de
REVIEW
Figure 3. a,b) Mechanism of SELF (a) and continuous strain step experiment (37 °C) (b) for the hydrogel, composed of telechelic difunctional
poly(ethylene glycol) (PEG) and glycol chitosan. Reproduced with permission.[76] Copyright 2015, Wiley-VCH. c–k) Photographs demonstrating the self-
healing process of acrylamide-modified chitin (AMC) and oxidized alginate hydrogels with (c–g) and without (h–k) fresh cuts at RT (20 °C). Self-healing
is shown at different time intervals (0 min, 60 min, and 180 min) and stretchability is also shown after 180 min of healing at RT (20 °C). Reproduced
with permission.[78] Copyright 2015, The Royal Society of Chemistry.
of the mechanical properties was observed after the hydrogels hydrogel together at RT (20 °C). The self-healing property could
were exposed to a ramping strain until the crosslinks failed be retained over several cycles of being cut, held back together,
(γ = 400%) at 25 °C.[39] Self-healing hydrogels could be formed and healing. Recovery of the mechanical properties at 25 °C was
by boronic ester networks via photoinitiated radical thiol–ene observed after 17 s at 50% strain after the gels were exposed to
click chemistry of the di- and tetrathiols 3,6-dioxa-1,8-octan- a strain ramp until the bonds failed (up to 387%).[80]
edithiol and pentaerythritol tetrakis(3-mercaptopropionate),
respectively with 4-((allyloxy)methyl)-2-(4-vinylphenyl)-1,3,2-
dioxaborolane (VPBE). The proposed mechanism, along with 3.2. Hydrogen Bonding
photographs of self-healing of the boronic ester network,
is illustrated in Figure 4.[40] After healing for 3 days at 85% Hydrogen bonding is a physical interaction that is much
humidity and RT (20 °C), these hydrogels were able to recover weaker than dynamic covalent and ionic crosslinks. When a
≈100% tensile strength (≈1.4 MPa) and ≈85% elongation at hydrogen atom is bonded directly to a highly electronegative
break after three cycles of tensile stretching. The theory behind atom (e.g., O, N, or F) partial positive and negative charges
the exchange of components between diols and boronic acids exist at the hydrogen and electronegative atom, respectively.
in the recovery of bonds was reflected in the long time (days) Reversible crosslinks form between different polymer chains
required for self-healing.[40] The same group also developed a by electrostatic interactions that occur between the hydrogens
SELF oxime-functionalized hydrogel formed via the copolymer- (hydrogen donors) and electronegative atoms (hydrogen accep-
ization of N,N-dimethylacrylamide (DMA) and diacetone acryla- tors) of different moieties. For example, the self-complementary
mide (DAA), and subsequent crosslinking with the difunctional quadruple hydrogen-bonding functionality of ureidopyrimi-
alkoxyamine O,O′-1,3-propanediylbishydroxylamine dihydro- dinone (Upy) units has been exploited in the development of
chloride. Hydrolytic cleavage of the oxime bond is reversible SELF hydrogels.[14,44,81–83] The SELF mechanisms lie with the
and provided the hydrogels with SELF properties. These gels quadrupole donor–donor–acceptor–acceptor (DDAA or ADDA)
exhibited self-healing after 2 h of holding two pieces of cut self-complementary hydrogen bonds that enable reversible
www.advmat.de
REVIEW
Figure 4. Self-healing property of a boronic ester network hydrogel. a) Proposed mechanism of complete healing. b) Photographs of the healing process
at 85% humidity and RT (20 °C). Reproduced with permission.[40] Copyright 2015, American Chemical Society.
supramolecular assembly. For example, Upy end-functionalized occurs within 2–5 min, but is restricted to ambient conditions
poly(ethylene glycol) (PEG) has been developed for use as an (pH range of 7–8 and 20 °C).[82,83]
injectable delivery system.[81] This Upy-functionalized hydrogel Hydrogen bonding occurs between the hydroxyl moieties of
exhibits complete self-recovery from alternate step-strain defor- adjacent chains in poly(vinyl alcohol) (PVA) hydrogels. When
mations (γ = 1 or 100) at 37 °C.[81] two severed PVA hydrogels are brought into contact, chains
The incorporation of the Upy moiety, grafted onto a diffuse across the interface from both sides to re-form the
polymer chain to form pendant or brush-like functional hydrogen bonds with the disappearance of the interface in the
groups, has been explored to facilitate SELF.[44] The monomer bulk after 12 h at RT (20 °C) (Figure 6a–e).[47] This self-healing
2-( N ′-methacryloyloxyethylureido)-6-(1-adamantyl)-4[1 H ]- hydrogel was able to recover 72% tensile stress at 48 h healing
pyrimidinone was copolymerized with N,N-dimethylacrylamide time (Figure 6f–g). However, the predominant self-healing
to form a SELF hydrogel. The adamantyl substituent creates abilities of PVA hydrogels are limited to less than 1 hour due
a hydrophobic pocket that protects the hydrogen bonds from to the rearrangement of the hydroxyl moieties in the forma-
the disruptive effect of water. A hydrogel that was injected tion of intra- or interchain hydrogen bonds. There is a decrease
through a 22-gauge syringe and then subjected to a fixed strain in the toughness of the self-healed hydrogels, which has been
amplitude in a rheometer (at 21 ± 1 °C) exhibited good restora- attributed to the possible loss of some water molecules during
tion of mechanical properties compared to those of a pristine the specimen manipulation required for the self-healing
sample.[44] A Upy-functionalized dextran hydrogel was shown experiment.[47] Self-healing (within 1 h) of a glutaraldehyde-
to self-heal within minutes at RT (20 °C) when the Upy den- crosslinked PVA and chitosan hydrogel is also attributed to
sity was sufficiently high. It possessed shear-thinning behavior, the spontaneous diffusion of PVA chains, chitosan chains, and
which enabled it to behave like a liquid under shear stress water at the interface, and subsequent hydrogen bonding. The
during injection and quickly regain its solid structure after hydrogel’s injectability (SELF ability) and pH sensitivity was
injection, forming a self-integrated structure (Figure 5a,b). The exploited in a drug-delivery and controlled-release system.[84]
dynamic modulus of the hydrogel was shown to recover after The role of hydrogen bonding was also responsible for self-
cyclic high (100 Pa) and low (0.1 Pa) stresses at RT (20 °C). The healing in a hydrogel formed by the in situ polymerization
self-healing, self-recovery, injectability, and biocompatibility of of acrylic acid and acrylamide in the presence of glycogen.[85]
the hydrogel were demonstrated in the successful fabrication Autonomous self-healing under ambient conditions was evi-
of a self-integrated scaffold to engineer a bone–cartilage tissue dent after 12 h due to hydrogen bonding between the carboxyl
complex.[14] Upy pendants have also been utilized in the self- and amide moieties of the acrylic acid and acrylamide groups.
healing mechanism of a hydrogel containing the copolymer However, pH studies have revealed that the autonomous self-
of 2-(dimethylamino)-ethyl methacrylate (DMAEMA) and healing is limited to neutral pH.[85] A hydrogel consisting of the
2-(3-(6-methyl-4-oxo-1,4-dihhydropyrimidin-2-yl)ureido)ethyl oligomeric electrolyte poly(pyridinium-1,4-diyl-iminocarbonyl-
methacrylate (SCMHBMA) (Figure 5c–e). DMAEMA is the 1,4-phenyle-nemethylene chloride) exhibited self-recovery of its
hydrophilic and predominant component whereas the SCM- mechanical properties 220 min at 25 °C after the cessation of a
HBMA contains the hydrophobic Upy unit. Rapid self-healing 30 min high shear rate of 1000 s−1. The self-recovery was due
www.advmat.de
REVIEW
Figure 5. Formation of Upy-functionalized dextran hydrogel, its injectability, and SELF properties at RT (20 °C). a) Dextran with no modification or
with low UPy density remains in solution state, while a DEX–UPy polymer with an high UPy density readily forms a hydrogel, and is injectable through
a 26-gauge needle (images left to right). b) Self-healing of the hydrogel pieces to form various structures. Some of the hydrogel disks were dyed with
rodamine (pink) and the others were left kept at their original color (yellow) to better visualize the interfaces. Scale bar = 5 mm. Reproduced with
permission.[14] Copyright 2015, Wiley-VCH. c) Chemical structure of the copolymer containing DMAEMA and SCMHBMA; d) the schematic model of
the self-healing and stretching of the DMAEMA and SCMHBMA copolymer hydrogel at ambient conditions; and e) the hydrogen-bonding Upy unit.
Reproduced with permission.[82] Copyright 2015, The Royal Society of Chemistry.
to chlorine-ion-mediated hydrogen bonding between the hydro- tripolyphosphate. These ionotropic stiff hydrogels can self-
gens of the amide groups and water.[86] heal when torn and present remarkable adhesion to both
A SELF hydrogel has been constructed from a DNA-grafted hydrophilic and hydrophobic substances under water. These
polypeptide and an ”X”-shaped DNA linker.[87] The revers- hydrogels are able to recover their mechanical properties
ible linkages occurred via precise DNA recognition (based on (after 10–30 minutes at RT, 20 °C) after deformation caused
hydrogen bonding). Freshly prepared hydrogels were shown by a strain amplitude sweep up to 200%.[88] A carboxylbetaine
to adhere to each other immediately and could be lifted up by acrylamide (AAZ) hydrogel exploits zwitterionic electrostatic
tweezers after several minutes at RT (20 °C). The self-healed interactions as the SELF mechanism.[42] This SELF ability of
hydrogel was able to restore 100% of its original mechanical this zwitterionic hydrogel did not change with regard to healing
strength after 5 min of healing. Continuous stress-relaxa- time at RT (20 °C). Physically crosslinked hydrogels generally
tion measurements (0.7 Pa or 1000 Pa) at 25 °C revealed that exhibit self-healing only of freshly cut surfaces that are imme-
the hydrogel was able to recover 100% mechanical behavior diately (within seconds) placed back together due to the sur-
(storage modulus) immediately and without fatigue. The face rearrangement and stabilization of moieties at the freshly
hydrogel exhibited shear-thinning behavior and was able to be cut surfaces (Figure 7a).[42] For example, time-dependent
injected through a needle and recover gelation after printing.[87] self-healing at RT is exhibited by hydrogen-bonded poly(vinyl
alcohol) (PVA) due to the rearrangement of the chains at the
surface.[47] This rearrangement allows their hydroxyl groups to
3.3. Ionic Bonding form either inter- or intrachain H-bonds to minimize the sur-
face energy. Consequently, over time, there is a decrease in the
The ionic SELF mechanisms occur via the reversible electro- number of ahydroxyl groups that are available to re-form the
static interactions of oppositely charged ions. This may involve hydrogen bonds between the two surfaces, and the self-healing
a charged polymer chain crosslinking with an oppositely diminishes or ceases to occur. In contrast, this zwitterionic
charged polymer chain or with oppositely charged ions. How- hydrogel exhibited spontaneous self-healing properties regard-
ever, depending on the experimental conditions, these may less of the time that had passed before the cut surfaces were
become deprotonated and result in electrostatic repulsion, hin- re-joined.[42] The zwitterionic surface is stabilized by a hydrated
dering SELF.[26] Certain combinations of polyelectrolytes and/ layer and the hydrophilic moieties remain exposed without rear-
or counter ions in aqueous solutions will interact and form a rangement. When pieces of the cut hydrogel are reconnected,
3D hydrogel network via ionic crosslinks. The physical nature the exposed moieties fuse across the boundary via zwitterionic
of these electrostatic interactions makes them ideal for exploi- fusion (Figure 7c–g). This self-healing hydrogel recovered 90%
tation as a SELF mechanism. The polycation poly(allylamine of its tensile strength (≈62 kPa before being cut) and mod-
hydrochloride) has been ionically crosslinked separately by ulus (≈24 kPa before being cut) immediately and after 24 h of
phosphate-bearing multivalent anions, pyrophosphate and healing at RT (20 °C). The healing efficiencies decreased with
www.advmat.de
REVIEW
Figure 6. Photographs demonstrating self-healing properties of poly(vinyl alcohol) (PVA) hydrogel at RT (20 °C). a) Two pieces of the original hydrogel
with (pink) and without (clear) rhodamine B. b) Two cut pieces of the original hydrogels. c) Self-healed hydrogel upon bringing the two pieces of
hydrogel into contact for 12 h in air at RT (20 °C) without any external stimulus. d) Bending of the self-healed hydrogel. e) Stretching of the self-healed
hydrogel to about 100% extension. f) Stress–strain curves of the original and the self-healed PVA hydrogel at various healing times at RT (20 °C) and
under a tensile rate of 1 mm s−1. g) Plot of the recovery (efficiency) of the tensile strength (fracture stress) of self-healed hydrogel vs healing time.
Reproduced with permission.[47] Copyright 2012, American Chemical Society.
increasing crosslinker concentration. This hydrogel also exhib- assemblies are held together by noncovalent interactions
ited impressive fatigue resistance and recovery, and was able (such as hydrogen bonding), the crosslinks are reversible and
to sustain 10 000 cycles of compressive deformation with no can be exploited as a SELF mechanism. For example, the 3D
significant difference to the modulus. Complete recovery of the truncated cone structure of cyclodextrins, cyclic oligosaccha-
mechanical properties was also observed from continuous step- rides composed of α-(1→4)-linked glucopyranoside units, has
strain deformation measurements at 25 °C (γ = 1 or 1000%).[42] been utilized as a reversible supramolecular host to facilitate
self-healing at RT (20 °C) (Figure 8a).[45] β-Cyclodextrin (host)-
functionalized poly(acrylamide) copolymerized with the hydro-
3.4. Supramolecular Interactions phobic monomer N-adamantane-1-yl-acrylamide (guest) formed
hydrogels (β-CD-Ad) that exhibited immediate and autonomous
Guest–host interactions are those that involve two or more chem- self-healing (Figure 8b) with complete restoration of the initial
ical species that cause molecular assembly via non-covalent com- adhesion strength achieved after 24 h at RT (20 °C). Changing
plementary inclusion binding. A unique structural relationship the hydrophobic guest monomer to n-butyl acrylate and host
exists, such that one moiety (the guest) is physically inserted and group to α-cyclodrextrin resulted in hydrogels (α-CD-nBu) with a
included inside another moiety (the host). As the supramolecular decrease in self-healing ability; i.e., only 74% of adhesion strength
www.advmat.de
REVIEW
Figure 7. Illustration and demonstration of zwitterionic-fusion-induced time-independent self-healing behavior at RT (20 °C). a) Different healing
behaviors of single-charged, non-ionic, and zwitterionic materials. b) Chemical structure of single-charged 7-acrylamidoheptanoate acid (AAS), control,
and non-ionic (hydroxyhexylacrylamide (AAN), control, and zwitterionic carboxybetaine acrylamide (AAZ). c) Illustration of construction process of a
block hydrogel from different colored AAZ hydrogels. d–g) Photographs of individual AAZ hydrogel blocks dyed with different colors (d), self-healed
hydrogel composed of the four different blocks of hydrogel (e), the self-healed hydrogel stretched (f), and the self-healed hydrogel upon bending (g).
Reproduced with permission.[42] Copyright 2014, Elsevier Ltd.
was regained after 24 h at RT (20 °C). The elastic modulus was Another example of a pendent guest–host interaction uti-
shown to be dependent on the association constant of the guest lized as a SELF mechanism was achieved by the radical copo-
hydrophobe, clearly demonstrating the effect that the choice of lymerization of N,N′-dimethylacrylamide functionalized with
moiety has on the hydrogel and self-healing properties.[45] The cholic acid and β-cyclodextrin.[68] Self-healing at RT (20 °C) was
same host–guest interaction was utilized in β-cyclodextrin- and achieved within less than 1 min and found to be dependent
adamantane-modified hyaluronic acid SELF (or adaptable) hydro- on the cross-sectional size of the applied damage, i.e., larger
gels. The hydrogels were capable of being injected after gelation areas of damage require greater healing times to reach com-
and rapidly regained solid behavior in situ.[89–92] Continuous step- plete self-healing. Rheological step-strain measurements at
strain experiments at 25 °C (3.5 cycles of 0.5% then 250% strain) 25 °C revealed that the hydrogel recovered 97% of its storage
revealed that the hydrogels were able to recover 100% storage modulus in 30 s at 10% strain after being placed under a large
modulus within 30 s.[90] The use of these hydrogels as “inks” for strain of 1000%. Plots of the variation of viscosity as a function
3D printing was successfully demonstrated. The hydrogel could of shear rate revealed a two-flow regime. At low shear rates,
be directly printed into SELF “support” hydrogels. The revers- the hydrogels exhibited shear-thickening until a maximum was
ible bonds of the guest–host interaction could be disrupted by reached. At higher shear rates the gel exhibited shear-thinning,
application of shear stress (extrusion through a nozzle), and associated with breakage of the guest–host interactions.[68]
was observed to re-form rapidly upon removal of the stress (on Rapid self-healing was achieved by the guest–host recogni-
the substrate after printing).[92] Tethering the β-cyclodextrin and tion between β-cyclodextrin-functionalized acrylamide and
adamantane to the hyaluronic acid via a peptide enabled pro- α-bromonaphthalene-functionalized acrylamide. Self-healing
tease-mediated degradation for controlled drug delivery. These was evident within 1 min of two cut pieces of hydrogel being
peptide-tethered hydrogels were also able to recover more than put back together and complete self-healing was exhibited after
95% of their initial storage modulus after 3 s following the 1 h at RT (20 °C).[93] Mixing the β-cyclodextrin-functionalized
applied deformation at 37 °C.[91] acrylamide and α-bromonaphthalene-functionalized acrylamide
www.advmat.de
REVIEW
ferrocene) exhibited 100% self-recovery of the

storage and loss moduli during continuous
step-strain-relaxation (γ = 0.1 and 100%)
experiments.[97] β-Cyclodextrin-functionalized
acrylamide, adamantane-functionalized
acrylamide, ferrocene-functionalized acryl-
amide and poly(N-isopropylacrylamide)/
poly(acrylamide) hydrogels also exhibited
self-healing within 2 h, at RT (20 °C) and
under “wet conditions”.[98] This hydrogel
obtained 68% healing efficiency based on
the restoration of the adhesion strength
after 72 h of healing. The hydrogel exhibited
redox-responsive behavior, i.e., redox stimuli
caused the uptake and release of water
causing the volume to expand and contract,
and resulted in shape-memory behavior.[98]
Polyelectrolyte hydrogels based on choles-
terol (Chol)-modified triblock poly(L-glutamic
acid)-block-poly(ethylene glycol)-block-poly(L-
glutamic acid) ((PLGA-b-PEG-b-PLGA)-g-
Chol) and β-cyclodextrin (β-CD)-modified
poly(L-glutamic acid) (PLGA-g-β-CD) were
capable of SELF.[99] After 1 min at RT
(20 °C) the hydrogel appeared to self-heal
and regained its original shape. An alternate
step-strain test at 25 °C revealed 100% self-
recovery within seconds. The SELF proper-
ties were attributed to the guest–host inter-
actions of cholesterol and β-cyclodextrin,
and this was exploited in the construction
of multilayered structures with potential
in tissue-engineering applications. Unlike
Figure 8. a) Preparation of the supramolecular hydrogels of host–guest interactions of
α-cyclodextrin-n-butyl (α-CD-nBu) and β-cyclodextrin-adamantine (β-CD-Ad). b) After standing
many of the acrylic-acid- and acrylamide-
for 5 s, two cut pieces of (β-CD-Ad) hydrogel were rejoined and the was crack sufficiently based cyclodextrin-based hydrogels, this
healed to form one hydrogel at RT (20 °C). Reproduced with permission.[45] Copyright 2013, hydrogel was shown to be biodegradable and
Wiley-VCH. biocompatible.[99]
Metal coordination interactions are those
with gold nanoparticles modified with 6-thio-β-cyclodextrin that involve a metal ion bound to a ligand (atom, molecules, or
produced hydrogels with rapid self-healing behavior. After ions that donate electrons) to form complexes with a preferred
placing two cut pieces of hydrogel together, the interface dis- coordination geometry. Hydrogels are formed by self-assembly
appeared after 1 min and mechanical characteristics (storage into supramolecular networks. The reversible nature of metal-
and loss moduli) were nearly completely recovered after 1 h coordinated bonds has been exploited in hydrogels formed by
of healing at RT (20 °C).[94] Poly(ethylene glycol) methyl ether the coordination of catechol-functionalized chitosan with Fe3+.
methacrylate (PEGMA)-grafted lignin hyperbranched copoly- Rapid self-recovery of the initial mechanical strength (storage
mers readily formed self-recovering hydrogels in the presence modulus) was observed in 100 s during continuous step-strain
of α-cyclodextrin. Continuous step-strain measurements at relaxation measurements at RT (20 °C).[100]
37 °C revealed the hydrogels were able to rapidly recover 100%
of their mechanical behavior (storage modulus) within 5 s.[95]
A self-healing hydrogel from the supramolecular arrange- 3.5. Hydrophobic Bonding
ment of β-cyclodextrin-functionalized acrylamide and ferrocene-
functionalized poly(acrylic acid) chains exhibited self-healing Hydrophobic interactions occur with the aggregation of hydro-
after 24 h at RT (20 °C).[96] The self-healing behavior was shown phobic surfaces or hydrophobes in aqueous media. Compact
to be controllable via redox treatments, i.e., application of an hydrophobic structures are easily formed and, when disturbed,
oxidizing or reducing agent to the freshly cut surfaces com- quickly re-form. Micelle copolymerization is one method that
pletely prevented or enabled, respectively, self-healing of the re- has been used to allow the incorporation of stable hydro-
joined surfaces.[96] A supramolecular hydrogel from poly (N,N- phobic domains into hydrogels without disrupting the hydro-
dimethylacrylamide-r-glycidol methacrylate-β-cyclodextrin) and philic nature. It involves the simultaneous polymerization of
poly( N , N -dimethylacrylamide- r -2-hydroxyethylmethacryl ate- hydrophilic monomers with a small quantity of hydrophobic
www.advmat.de
REVIEW
monomers that subsequently form micelles. The rearrange- exhibited when the hydrogels were cut in half and the halves
ment of the hydrophobic associations of micelles forms the placed back together for 10 min at 24 °C (Figure 9b–e), and
basis of a SELF mechanism. This strategy has been used in these hydrogels exhibit 100% healing efficiency with regard to
a SELF hydrogel, with octyl phenol polyethoxy ether acrylate the elongation-at-break ratios after 20 min at 24 °C (Figure 9f).
hydrophobic monomers incorporated into a hydrophilic acryla- These hydrogels exhibited 100% recovery of their mechanical
mide hydrogel.[101,102] Micelles were formed by associations characteristics after cyclic compression deformations.[70] The
between the hydrophobic acrylates and sodium dodecyl sul- addition of NaCl salt led to the growth of wormlike micelles
fate (SDS). A cylindrical sample was cut, and the halves were and aided in the hydrophobe’s inclusion into the hydrophobic
placed back together (submerged in water at RT, 20 °C) in a poly(acrylamide) network. The role of SDS in solubilizing
closed plastic pipe. Approximately 70% efficiency (tensile strain (weakening the hydrophobic associations) proved vital in con-
at break) was exhibited after 3 days of healing. 100% recovery of trolling the reversibility of the associations, and the subsequent
the mechanical characteristics was exhibited after the cessation self-healing and mechanical properties. Free blocks of C18
of a large deformation (1000% strain) at ≈75 min at 25 °C. Self- (those not involved in hydrophobic associations) were para-
healing was initiated by the formation of a monolayer mem- mount in the self-healing.[64,70] Hydrogels formed without the
brane at the cut interface formed by the SDS of the dissociated addition of SDS behave like gels that are covalently crosslinked,
micelles. The hydrophobic monomers would then interact with i.e., they do not possess self-healing properties.[70] Utilizing
the SDS to re-form micelles. The self-healing, mechanical, and n-alkyl (meth)acrylates of various lengths and concentrations
remoldable properties are attributed to the dissociation and re- as the hydrophilic monomer produced hydrogels with varying
association of the micelle crosslinks.[102] degrees of self-healing ability.[103] An increase in healing effi-
Okay and co-workers developed similar mechanisms that ciency (29 to 34%) at 25 ± 0.5 °C was obtained with an increase
employ reversible crosslinking, required for autonomous in the alkyl chain length (C16 to C18), and a maximum healing
SELF.[46] SELF hydrogels were formed via the micelle copo- efficiency (34%) was achieved for the hydrogel composed of
lymerization of hydrophobic monomer, stearyl methacrylate the hydrophobe of 18 carbons. The self-healing could be fur-
(C18), with the hydrophilic monomer acrylamide (AAm) in an ther increased (88% for C18) by incorporating methacrylates
aqueous solution of SDS/NaCl (Figure 9a).[70] Self-healing was into the hydrogels, as compared to the corresponding acrylates
Figure 9. a) Illustration of the self-healing hydrogel formed via the micelle copolymerization of hydrophobic stearyl methacrylate (C18) with the hydro-
philic monomer acrylamide (AAm) in an aqueous solution of SDS/NaCl. b–e) Photographs of the hydrogel: cut into two pieces (b,c), the fractured
surfaces pressed together for 10 min at 24 °C (d), and the self-healed hydrogel that can be stretched without breaking (e). f) Elongation ratio at break
of healed gel samples (λb) shown as a function of the healing time at 24 °C. The horizontal line and the dashed area represent the mean value and the
standard deviation for the virgin hydrogel sample. Reproduced with permission.[70] Copyright 2012, American Chemical Society.
www.advmat.de
REVIEW
(34% for C18). The greater extent of self-healing ability was and weak nature of SELF hydrogels limits their use in stress
attributed to the limited flexibility of the backbone chain and and load-bearing applications such as soft robotics.[107] Conse-
a consequent increase in the number of the free hydrophobic quently, there is a push to develop mechanically robust SELF
blocks. The self-recovery for these gels reached 100% within hydrogels.[64] In general, the mechanical characteristics have
2 min after cyclic compression deformations at 25 ± 0.5 °C.[103] been improved via the development of SELF hydrogels that
An alternative approach to grow wormlike micelles is to use incorporate multiple crosslinking mechanisms, such as those
a combination of oppositely charged surfactants. Mixtures of used in (nano)composites, and in hybrid and interpenetrating
the anionic surfactant SDS and the cationic surfactant cetyl- polymer network (IPN) hydrogels.[108]
trimethylammonium bromide (CTAB) induce micelle growth,
increase hydrophobe solubility, and enhance the mechanical
properties of the self-healing hydrogel. An increase in micelle 4.1. (Nano)composite Hydrogels
size caused an increase in the degree of temporary spatial inho-
mogeneity and lifetime of the hydrophobic associations, and Composites and nanocomposites are materials that are com-
simultaneously decreased the elongation at break ratios. An posed of immiscible organic (polymer) and inorganic compo-
average healing efficiency of 98% was exhibited after healing nents (clays/particles) with complex (nanometer) structures.
for 60 min at 35 °C.[104] Using poly(N-isopropylacrylamide) The clays are not just dispersed into the polymer network,
as the hydrophilic monomer and cetyltrimethylammonium but act as multifunctional crosslinks. Healable, recoverable,
bromide (CTAB) as the surfactant produced SELF hydrogels. stable, and stiff nanocomposite hydrogels have been devel-
Healing efficiencies of 100% were obtained after 30 min of rest oped using a three-component hydrogel architecture consisting
at 24 °C.[105] Hysteresis from cyclic loading/unloading cycles of: i) poly(vinyl alcohol) functionalized with methyl viologen
(compression) up to large maximum strains (90%) was 100% (PVA-MV), ii) cellulose nanocrystal (CNC) colloidal rods con-
recovered after 5 min of sample resting at 24 °C, and this indi- taining copolymer grafts of protonated dimethylaminoethyl
cates that the damage done was recoverable in nature. When methacrylate and nephthyl methacrylate (CNC-g-P(DMAEMA-r-
swollen, these hydrogels lose their self-healing ability due to the NpMA), and iii) cucurbit[8]uril (CB[8]) (Figure 10a–c).[109] CB[8]
leakage/loss of surfactant, and subsequent strengthening of the simultaneously binds the methyl viologen (MV) and nephthyl
hydrophobic interactions. However, hydrogels, swollen or not, (NP) of components i and ii, respectively, together in host–
exhibit self-healing with the inclusion of acrylic acid mono- guest reactions (Figure 10c,d). These nanocomposite hydrogels
mers, which is due to the additional ionic interactions between exhibit significant mechanical strengths and stiffness with a
the acrylic acid and the CTAB.[105] storage modulus of >10 MPa. Immediate self-recovery was
A self-recovering hydrogel formed of short peptides self- shown via step-strain measurements at 25 °C and rapid self-
assembled into nanoscale amyloid fibrils was developed as a healing abilities were observed at RT (within 30 s). A broken
scaffold for tissue engineering.[106] The amyloid fibrils con- hydrogel kept apart for 4 months was able to rapidly self-heal
sist of highly repetitive cross-β-sheets and a 3D hydrogel net- (within 10 s) once re-joined (Figure 10e,f). The SELF was attrib-
work is formed by the combination of hydrophobic and π–π uted to the cleavage and reassembly of the guest–host inter-
interactions and hydrogen bonding. Complete recovery of the actions.[109] Hydrogels prepared by blending nanofibrillated
mechanical characteristics was exhibited after alternate step- cellulose (NFC), poly(vinyl alcohol) (PVA), and borax have been
strain measurements (γ = 0.5 or 100%) at 25 °C. Hydrogels vor- shown to exhibit self-healing behavior.[110] The hydrogels were
texed for 5 min were converted to the solution state, and their able to be broken apart and re-form into a single piece at RT
gel state was recovered autonomously after 10–15 min at RT (20 °C). Deformations caused the breakage of the tetrahedral
(20 °C). The self-recovery mechanism is attributed to reversible PVA–borax complexes, NFC chain entanglement, and hydrogen
sticky hydrophobic surfaces of the fibrils.[106] bond interactions between NFC–NFC, NFC–PVA, and trigonal
PVA–borax. The re-formation of some of the hydrogen bonds
was responsible for the self-healing ability and enhanced
4. Tough SELF Hydrogels mechanical properties of these hydrogels.[110] Negatively
charged hyaluronic acid and carboxymethylcellulose (CBMC)
The SELF ability of a hydrogel is generally inversely proportional were adsorbed onto biodegradable nanoparticles comprising
to its mechanical strength. Increasing efficiencies and recoveries of poly(ethylene glycol)-b-poly(lactic acid) (PEG-b-PLA) to form
are achieved with a decrease in the lifetimes of the reversible a self-recovering hydrogel.[111] The electrostatic interactions
crosslinks. In contrast, good mechanical characteristics (think between the biopolymers and nanoparticles were enhanced by
cartilage) are achieved by strengthening the crosslinks. Further- the use of a positively charged surfactant, CTAB. At 25 °C, these
more, the design of tough hydrogels is based on the dissipation hydrogels were able to restore 100% mechanical characteristics
of mechanical energy to reduce the propagation of crack forma- (storage modulus) within 20 s after deformation at a high shear
tion.[59] Swelling of polymers, as in hydrogels, decreases the rate of 100 s−1.[111] Other hydrogels composed of cellulose nano-
number of polymeric chains per unit cross-sectional area and whiskers, acrylamide, stearyl methacrylate, and SDS were able
consequently reduces the number of chains needed to advance to self-heal due to the dissociation and re-association of hydro-
the crack or the number of chains available for viscoelastic phobic micelles.[112] Nearly 100% healing efficiencies (tensile)
energy dissipation. Thus, in general, highly swollen conven- were exhibited after 60 min of healing. The network exhibited
tional hydrogels do not possess the efficient energy-dissipation high extendibility of up to 2500%, and high tensile and com-
mechanism that is required for toughness.[48] The current soft pressive strengths of 1.338 MPa and 2.835 MPa, respectively.[112]
www.advmat.de
REVIEW
Figure 10. Schematics and architecture for the three-component hydrogel architecture consisting of: a) poly(vinyl alcohol) functionalized with methyl
viologen (PVA–MV), b) cellulose nanocrystal (CNC) colloidal rods containing copolymer grafts of protonated dimethylaminoethyl methacrylate and
nephthyl methacrylate (CNC-g-P(DMAEMA-r-NpMA), and c) cucurbit[8]uril (CB[8]). d) The supramolecular crosslinks based on the three-component
recognition of CB[8]. e) Self-healing immediately after cutting at RT (20 °C): 1) original hydrogel, 2) hydrogel cut in two pieces, 3) self-healing by
bringing the two cut pieces together for 30 s immediately after the cutting, 4) subsequent stretching of the material, and 5) a new point of failure.
f) Self-healing after 4 months of storage: 1,2) the pieces were brought together for 10 s and stretched until breakage occurred at new point of failure
(3–6). Reproduced with permission.[109] Copyright 2014, Wiley-VCH.
Graphene oxide sheets have been used physical crosslinks between the acrylamide chains, and between the acrylamide
in a hydrophobic-associated poly(acrylamide) composite and graphene oxide sheets.[114] Significant degrees of self-
hydrogel.[113] The hydrogels exhibit high strength with a tensile healing in terms of fracture tensile stress (88%), breaking
stress of 243 kPa and high extendibility with elongations up tensile strain (92%) and elastic (Young’s) modulus (100%)
to 1990%, and high toughness was demonstrated with a dis- were achieved after 24 h of healing at 30 °C. This composite
sipated energy of up to 263 kJ m−3. The hydrophobic-associated possessed enhanced mechanical strength and could withstand
poly(acrylamide) was able to reconstruct without any external large elongations (49 times). This was found to be dependent
stimulus and the hydrogels exhibited self-healing (53% tensile on the physical crosslinks between the graphene oxide sheets
healing efficiency) and fatigue resistance (up to 51% recovery and acrylamide.[114] Graphene oxide nanosheet and poly(acrylic
of energy dissipation following successive loading/unloading acid) composite hydrogels crosslinked by Fe3+ ions exhibited
cycles).[113] A graphene oxide and poly(acrylamide) composite self-healing behavior at 45 °C for 48 h, i.e., ≈60% and ≈80%
hydrogel was observed to exhibit self-healing via mutual tensile stress and strain healing efficiencies, respectively.[115]
diffusion and entanglement of polymer chains across the 86.8% recovery of hysteresis was exhibited after 48 h from cyclic
broken interface, followed by subsequent hydrogen bonding tensile tests. It was suggested that the reversibility of the ionic
www.advmat.de
REVIEW
interactions endowed the SELF and is crucial in the efficient of brucite Mg(OH)2 octahedra sandwiched in between layers
dissipation of energy (11.9 MJ m−3) when subjected to stress. of tetrahedral silicate with covalently linked aminopropyl moi-
These hydrogels also exhibited high tensile strength (777 kPa) eties. Reversible hydrogen bonding occurs between the ami-
and stretchability (elongation at break of 2980%).[115] nopropyl group of the organoclay and the amide moiety of the
Nanocomposite hydrogels composed of either poly(N,N- PVP. The integration of mesostructured building blocks ena-
dimethylacrylamide) (PDMAA) or poly(N-isopropylacrylamide) bled the hydrogel to retain and release drugs and biologically
(PNIPA), crosslinked with exfoliated 1 nm synthetic hectorite active molecules via guest–host interactions. The sequester and
nanoplatelets were shown to exhibit self-healing properties at assembly of guest molecules is driven by the electrostatic inter-
ambient temperature (20 °C) without external stimuli. The nan- actions between the cationic organoclay nanosheets and anionic
oplatelets were dispersed and linked via reversible hydrogen guest molecules (e.g., ibuprofen).[121]
bonding with the polymer chains. Stabilization via surface Autonomous self-healing hydrogels using nanocomposite
rearrangement of exposed moieties was not exhibited with brushes, formed by the surface polymerization of acrylic acid
self-healing properties, evident after long periods of waiting on vinyl hybrid silica nanoparticles, have also been demon-
(>120 h). Increased healing rates were facilitated by heat strated.[122] The healing was achieved by the simultaneous diffu-
(100% tensile stress/strain in 20 min at 80 ºC) and addition of sion of ferric ions and poly(acrylic acid) across the macroscopic
dimethylsulfoxide (DMSO).[116] Montmorillonite exfoliated ani- interface, followed by their subsequent entanglement and,
onic clay nanoplatelets have been utilized as multifunctional finally their association via hydrogen bonding and ferric-ion-
crosslinks in a poly(acrylamide) to produce SELF hydrogels.[117] mediated ionic interactions. The hydrogel (80% water) exhib-
These hydrogels exhibited remarkable stretchability with a frac- ited high toughness and stretchability with tensile strengths of
ture strain of up to 11 800%. However, autonomous self-healing 860 kPa and elongation at break of 2300%. Approximately 23%
was weak, i.e., healing was easily disrupted at the interface and (tensile stress) and 52% (tensile stain) healing efficiencies were
required multiple dry–reswell treatments to reach completion. achieved after 24 h at 25 °C. The self-healing was evident without
The hydrogels exhibited 100% recovery (after 5 days at 25 °C) an external stimulus, but was enhanced (≈65% initial tensile
of their mechanical characteristics from cyclic tensile deforma- strength and ≈78% initial tensile strain) by the addition of heat
tions. The SELF properties were attributed to hydrogen bonding (50 ºC) and increasing the healing time to 48 h.[122] Gerth et al.
between the platelet sheets and the poly(acrylamide).[117] A reported a multiple physically crosslinked self-recovery mecha-
similar montmorillonite/sodium polyacrylate network was nism involving metal coordination and hydrogen bonding.[123]
entangled with methyl-guanidine hydrochloride functional- Multivalent tectons were created by the spontaneous adsorp-
ized xylose (Figure 11a) to form a self-healing hydrogel at RT tion of terpyridine-end-capped poly(ethylene glycol) onto silica
(20 °C).[118] It was suggested that the gelation and self-healing nanoparticles. Composite hydrogels were subsequently formed
mechanisms occur via the reversible noncovalent interac- by the coordinated assembly of these tectons by Co(II). Greater
tions of the hydrogen bonds and the reversible electrostatic than 90% recovery of storage modulus was exhibited after large
adsorption between the guanidine hydrochloride pendants deformations during rheological measurements performed at
and the clay nanoplatelets.[118] Self-recovering hydrogels have 23.5 °C. The self-recovery mechanism involved the transient
also been formed by the addition of ferric ions to an aqueous metal–coordination linkages between the tectons and hydrogen
solution of exfoliated montmorillonite clay sheets coated with bonding between the polymer and nanoparticle.[123] Hydrogels
poly(dopamine).[119] The hydrogels were able to recover 70% of formed from the triblock copolymer of dimethylaminoethyl
their mechanical characteristics within 600 s during alternate methacrylate (DMAEMA) and ethylene oxide (EO) in aqueous
step-strain deformation measurements performed at 23 °C. It nanoclay dispersions of LAPONITE and Pluronic P127 expo-
was shown that self-recovery occurred by the reversible coordi- sure to CO2 exhibited 100% self-recovery after ≈100 s, shown
nation bonding between the ferric ions and the catechol moie- via alternate step-strain deformation tests (γ = 0.1 or 80%) per-
ties of the functionalized clay sheets.[119] formed at 25 °C.[124] The recovery can be explained as follows:
A nanoclay/dendritic macromolecular hydrogel was observed the hydrophobic poly(propylene oxide) blocks of the Pluronic
to self-heal at RT (20 °C) (Figure 11b,c) and rapidly self-recover F127 adsorb onto the surface of the LAPONITE nanoclays
via oscillatory continuous step-strain measurements performed leaving the hydrophilic PEO segments to dangle free. The steric
at 20 °C.[120] The mechanism of SELF is achieved as follows. First, hinderence of the PEO enables the exfoliation of the nanoclay.
dendritic macromolecules were functionalized with multiple In the presence of CO2, the amine groups of the DMAEMA
guandinium-ion pendants on the peripheries (Figure 11b). The become protonated and form ionic interactions with the nega-
functionalized dendritic macromolecules that are positively tively charged surface of the nanoclay.[124]
charged can than attach via ionic electrostatic interactions onto
the surface of the clay nanosheets with a negatively charged sur-
face and a positively charged edge. This is then re-dispersed in 4.2. Physical Multi-Mechanism Single-Network SELF Hydrogels
an entangled solution of sodium polyacrylate (Figure 11c).[120]
Other examples include a poly(vinylpyrrolidone) (PVP)/organ- Several physical networks employ the use of multiple
oclay nanocomposite hydrogel with self-healing ability that crosslinking mechanisms in the one miscible network. Gulyuz
was developed for drug delivery (Figure 11d).[121] The complex and Okay developed fully physically crosslinked SELF hydrogels
structure is composed of synthetic aminopropyl-functionalized that exhibit a high tensile strength of 0.7–1.7 MPa, a stretch at
magnesium phyllosilicate exfoliated organoclays. These nano- break of 800–900% and shape-memory properties.[125] Healing
clays possess a mesolamellar structure based on a central layer efficiencies of 100% and 30% were exhibited after 30 min (25 °C)
www.advmat.de
REVIEW
Figure 11. The gelation, self-healing process, and shape properties of several (nano)composite hydrogels. a) Sodium polyacrylate, exfoliated mont-
morillonite nanoplatelets, and methylguanidine functionalized xylose hydrogel (1) was cut in half (2), and the pieces that were held back together for
a few minutes at RT (20 °C) (3). once healed, were able to support their own weight (4). Reproduced with permission.[118] Copyright 2015, The Royal
Society of Chemistry. b) Dendritic macromolecules functionalized with multiple guandinium ion pendants on the peripheries (G3-binder). Reproduced
with permission.[120] Copyright 2015, Macmillan Publishers Ltd. c) Proposed mechanism for hydrogelation of sodium polyacrylate (ASAP), exfoliated
clay nanosheets (CNSs), and guanidinium-functionalized dendritic macromolecule hydrogels. CNSs, entangled with one another (1), are dispersed
homogeneously by interaction of their positively charged edge parts with anionic ASAP (2). Upon addition of Gn-binder, exfoliated CNSs are crosslinked
to develop a 3D network (3). Optical images of an aqueous suspension of CNSs (4), an aqueous dispersion of CNSs and ASAP (5), and a physical gel
upon addition of G3-binder to the dispersion (6). Reproduced with permission.[120] Copyright 2015, Macmillan Publishers Ltd. d) Poly(vinylpyrrolidone)
(PVP) and aminopropyl-functionalized magnesium phyllosilicate exfoliated organoclay hydrogel was prepared without (1) and with (3) ibuprofen,
and moulded into a transparent macroscopic object (2). Self-adhesion of freshly cut pieces was evident immediately (4) and after 3 h at RT (20 °C)
(5). 6–8) Swelling behavior of hydrogel after 0 h (6), 24 h (7) and 72 h (8). Reproduced with permission.[121] Copyright 2011, Wiley-VCH.
with regard to the modulus and fracture stress, respectively. The to autonomously self-heal.[125] The micelle copolymerization of
healing efficiency (fracture stress) increased to 75% with an poly(acrylic acid) and stearyl methacrylate in aqueous solutions
increase in temperature (80 °C). 100% hysteresis was recovered of SDS and NaCl produced hydrogels that exhibited enhanced
in 5 min during cyclic compression measurements (25 °C). The autonomous self-healing at 23 ± 2 °C (60% in 30 min) com-
hydrogels’ single network was formed by the copolymerization pared to poly(acrylamide) (0% in 30 min) hydrogels prepared
of stearyl methacrylate and acrylic acid in an aqueous solution under identical conditions.[126] Both hydrogels possess the same
of cationic surfactant CTAB and NaBr. The stearyl methacrylate reversible micelle crosslinks; however, the carboxyl groups of
and CTA+ form hydrophobic crosslinks in the form of micelles the poly(acrylic acid) undergo hydrogen bonding, which stabi-
and the CTA+ (at the outer edge of the micelle) ionically inter- lizes the hydrophobic domains. The hydrogels prepared with
acts with the oppositely charged poly(acrylic acid). The CTAB poly(acrylic acid) also exhibited self-recovery of their mechan-
was shown to weaken the hydrophobic crosslinks and extrac- ical characteristics during cyclic measurements of increasing
tion of the free CTAB after gelation (hydrogels in equilibrium elongations.[126] Algi and Okay utilized poly(N,N-dimethylacryl-
with water) was shown to increase the mechanical performance amide) (PDMA) in another micelle copolymerized hydrogel that
of the hydrogels. However, these hydrogels were no longer able exhibits self-healing and self-recovery at 24 °C.[65] 100% healing
www.advmat.de
REVIEW
efficiencies with regard to modulus and fracture stress/strains re-form), while the chemical crosslinks are there to provide
are achieved after 2 and 20 min, respectively. The hydrogels are structural and mechanical strength. For example, a network
able to recover 100% hysteresis after 7 min from cyclic compres- consisting of poly(dodecyl glyceryl itaconate) (PDGI) within
sion and tensile tests. The hydrogel is crosslinked by hydrogen a chemically crosslinked poly(acrylamide) (PAAm) network
bonding in addition to the hydrophobic micelles. The combi- possess hysteresis, self-recovery (100% tensile hysteresis after
nation of the hydrophobic interactions with hydrogen binding 15 min rest), fatigue resistance, and crack-blunting properties.[57]
results in the hydrogels possessing enhanced stretchability, The separate PDGI network forms hydrophobic-associated
which is not obtained by conventional PDMA hydrogels. These lamellar bilayers within the PAAm network and acts as revers-
PDMA hydrogels could reach 43 times their original length.[65] ible sacrificial bonds to enhance the toughness.[57] Okay and
A zwitterionic-based hydrogel of acrylamide and 3-((2-(meth- co-workers developed a hybrid hydrogel with enhanced mechan-
acryloyloxy)ethyl) dimethylammonio)propane-1-sulfonate ical properties, as well as self-healing and self-recovery.[128] The
(DMAPS) was shown to exhibit rapid self-recovery at 25 °C.[41] hydrogel was formed by the copolymerization of acrylamide and
Reversible electrostatic interactions existed between the zwit- stearyl methacrylate, and simultaneous covalent crosslinking
terionic DMAPS moieties, and hydrogen bonding between with N,N′-methylenebis(acrylamide). The hydrogel was com-
acrylamide moieties. The hydrogel’s rapid recovery (<9 s) posed of permanent covalent and reversible hydrophobic
was predominantly attributed to the interactions between crosslinks. The hybrid gels exhibited an 80% healing efficiency
the DMAPS moieties, while the hydrogen bonding provided (tensile modulus) after 60 min and 100% recovery of hysteresis
strength.[41] A rapid self-healing hydrogel was developed, which in 14 min from cyclic tensile loading/unloading at 24 ± 1 °C.
was composed of genetically engineered, amphiphilic, elastin- The hybrid gel was able to withstand compressive stresses
like polypeptides (ELP) with the amino acid sequence MG- of more than 24 times and 4 times greater those of the indi-
(VPGVG)60(VPGAGVPGGG)30HEDGHWDGSEHGY-G.[67] The vidual chemically and physically crosslinked hydrogels, respec-
ELPs assembled into micelles with the large hydrophobic block tively. However, these hybrid hydrogels do not possess the same
at the center of the micelle, and the exposed hydrophilic block stretchability of the respective physical hydrogel (without cova-
terminus was decorated with metal-coordination motifs on the lent crosslinks). Autonomous self-healing was evident only in
coronae. The micelles are stabilized by hydrophobic and van der hydrogels with low crosslink density. For hydrogels that had a
Waals interactions, and the micelles are crosslinked by coordi- high crosslink density a decrease in mobility/flexibility of the
nation with Zn2+. These hydrogels exhibited ≈90% healing effi- hydrophobes in the inhomogeneous network structure was
ciency (compressive stress) after 1 min of healing at RT (20 °C). attributed to the loss of self-healing ability.[128]
These hydrogels exhibit enhanced mechanical properties with a A hybrid SELF hydrogel was developed from poly(acrylic acid)
storage modulus of ≈1 MPa, which is attributed to the efficient (PAAc) simultaneously crosslinked by the covalent crosslinker
dissipation of energy obtained with the breaking and subse- N,N -methylenebisacrylamide and cerium ions.[129] SELF was
quent partial reformation of the reversible linkages.[67] attributed to the reversible ionic interactions while the cova-
A self-healing double covalently crosslinked hydrogel was lent crosslinks provided the mechanical support. Self-healing
designed by integrating Diels–Alder and dynamic acylhydra- was demonstrated and tensile healing efficiencies reached 80%
zone interactions.[127] The hydrogel consisted of furylamine- after 6 h healing at RT (20 °C). Near-complete microscopic self-
and adipic-dihydrazide-functionalized hyaluronic acid, and healing was observed by the disappearance of surface damage
furylamine-functionalized and oxidized hyaluronic acid. Diels– on thin films (observed via a microscope over 12 h). In addi-
Alder chemistry occurred between the furan and maleimide, tion, the hydrogel recovered immediately from alternate step-
which provides the network with mechanical integrity. Revers- strain measurements (10% and 600% strains).[129] An ionically
ible acylhydrazone bonds occur between the acylhydrazine crosslinked alginate network and N,N -methylenebisacrylamide
and the aldehyde and provide the self-healing mechanism of covalently crosslinked poly(acrylamide) network were joined
the hydrogel. The acylhydrazone bonds are known to be pH by covalent crosslinks to form a hybrid hydrogel that exhibited
responsive and the gel will transition to the solution state at self-recovery properties, high toughness (fracture energies of
pH < 4. This pH-responsive sol–gel transition was not observed ≈9000 J m−2) and high stretchability (stress and stretch at rup-
with the double-crosslinked hydrogel. Complete healing was ture of 156 kPa and 23 cm (>20 times initial length), respec-
exhibited after 3 h at ambient temperature (20 °C) with little tively).[130] As the hydrogel is stretched, the ionic alginate net-
difference between the compressive storage modulus (≈18 kPa) work unzips progressively and the covalent poly(acrylamide)
of the pristine and healed samples (100% healing efficiency). network remains intact, bridges the crack, and stabilizes defor-
This self-healing hydrogel was also shown to adhere to cartilage mation. The hybrid hydrogel exhibited pronounced hysteresis
via a Schiff base reaction between the aldehyde groups of the after it was loaded to a maximum stretch and unloaded to zero
hydrogel and the amines of the local cartilage tissue.[127] force. The gel was able to autonomously recover hysteresis
“somewhat” after 1 day at 20 °C during cyclic tensile loading/
unloading. Recovery of hysteresis was increased to 74% when
4.3. Hybrid SELF Hydrogels the hydrogel was left to heal at 80 °C for 1 day. The ionic net-
work re-forms and self-recovers the internal damage.[130] N,N′-
Hybrid networks are composed of both chemical and physical methylenebisacrylamide covalently crosslinked poly(acrylic
crosslinks in the one network in order to improve mechanical acid) and ferric ions have been used in a hydrogel that exhibits
toughness. Generally the physical crosslinks are designed to SELF via reversible ionic interactions.[43] The hydrogel exhibited
be sacrificial (i.e., to break upon the event of damage and then a healing efficiency of 88% after 6 h of healing at RT (20 °C).
www.advmat.de
REVIEW
Figure 12. a–i) The hybrid poly(acrylic acid) and ferric ion (PAA/Fe3+) self-healing hydrogel at RT (20 °C). a) Schematic illustration of the structure
of the PAA/Fe3+ ICE hydrogel. b–f) Self-healing and stretching of a cylindrical PAA/Fe3+ ICE hydrogel. g–i) Optical microscopy photographs of the
PAA/Fe3+self-healing hydrogel film dried on a glass surface. Reproduced with permission.[43] Copyright 2013, Wiley. j–q) The hybrid network hydrogel
formed from the copolymerization of PU–PEGMA and SCMHBMA. j–m) Self-healing and stretching of a cylindrical PU–PEGMA/SCMHBMA hydrogel
at ambient temperature (20 °C). n–q) Optical microscopy photographs of the self-healing PU–PEGMA and SCMHBMA hydrogel. Reproduced with
permission.[131] Copyright 2014, The Royal Society of Chemistry.
The gels showed 100% recovery (immediately) of mechanical after 10 min at ambient temperature (20 °C) (Figure 12j–m
characteristics during alternate step strain deformations (γ = 5 and 12n–q, respectively).[131] Other hydrogels were formed by
or 400%) performed at 25 ± 0.1 °C. The healing and recovery is the tris(bipyridine)ruthenium(II)-chloride-mediated covalent
attributed to the reversible ionic bonding between the ferric ions crosslinking of suckerin-19 (a block-copolymer-like structural
and the carboxylic groups of the poly(acrylic acid) (Figure 12a–i). protein).[132] Suckerin-19 is composed of a β-sheet structure
An increase in the degree of physical crosslinking was shown that is mediated by extensive hydrogen bonding, and possesses
to cause a decrease in the elastic properties of the hydrogel. large tyrosine content. Tyrosine readily forms dityrosine and
The self-healing was shown to be dependent on the degree of forms the basis of the covalent linkages in the hydrogel. Ampli-
covalent crosslinking, with increases in covalent crosslinking tude-strain-sweep measurements performed at 20 °C reveal
reducing the mobility of the polymer chains, and slower diffu- the hydrogel is able to completely self-recover its mechanical
sion of the ferric ions. However without covalent crosslinking, properties (storage modulus) within 30 s. The self-recovery
the hydrogels lacked mechanical strength and self-healing was behavior is attributed to the disassociation and re-association of
mostly due to the viscosity.[43] the β-sheets (hydrogen bonds).[132] A single network of (N,N′-
A hybrid network hydrogel was formed from the copoly- methylenebisacrylamide) covalently crosslinked carboxymethyl
merization of poly(ethylene glycol) methacrylate end-capped chitosan and acryloyl-6-aminocaproic acid was shown to self-
urethane ether prepolymer with 2-(3-(6-methyl-4-oxo-1,4-dihydro- heal (66% and 85% of tensile stress and strain, respectively) in
pyrimidin-2-yl)ureido)ethyl methacrylate (SCMHBMA) bearing less than 1 h in mild conditions. The self-healing ability was
Upy (2-ureido-4-pyrimidone) pendant units.[131] The rapid self- due to the extensive hydrogen bonding.[133] An amphiphilic
healing at ambient temperature (20 °C) (80.2–86.6% tensile molecule composed of a lauryl tail (hydrophobic), a peptide
stress in 10 min) was due to the quadrupole hydrogen bonding center block, and an amide-capped end block (hydrophilic) was
of the Upy units, and the chemical crosslinking provided the covalently crosslinked via glutaraldehyde to form a self-recov-
elasticity and mechanical support to sustain the hydrogel ering hydrogel.[134] Amplitude strain sweeps (up to 1000%)
shape. The self-healing properties were demonstrated by the revealed the hydrogel was able to recover most of the reversible
disappearance of the interface of two merged hydrogel pieces linkages within 10 min at 4 °C. The amphiphilic molecules self-
and the disappearance of an incision made to hydrogel films assembled into nanofibers directed by the hydrogen bonding
www.advmat.de
and subsequent β-sheet structure formation of the peptide

REVIEW
and rapid. 100% mechanical characteristics were recovered in

sequence. The lauryl tails promoted reversible hydrophobic less than 6 s during alternate step-strain measurements (γ = 1
interactions. The reversible linkages endowed the hydrogel with or 500%) performed at 37 °C. The hydrogel was shown to self-
self-recovery while the covalent crosslinks provided increased heal when cut and the halves placed back together immedi-
mechanical stability compared to the corresponding hydrogel ately (without leaving time to heal). This SELF hydrogel exhib-
without covalent linkages.[134] ited shear-thinning and bio-antifouling properties with poten-
tial use in bioengineering applications.[21] A fully physical
poly(dodecyl glyceryl itaconate) (PDGI) and polyacrylamide
4.4. Interpenetrating Polymer Network (IPN) SELF Hydrogels (PAAm) IPN was developed, which self-recovered.[52] Greater
than 90% recovery of the mechanical characteristics during
Chemical crosslinks increase the mechanical strength of a cyclic tensile loading/unloading was exhibited within 30 min
hydrogel but limit the SELF ability. Incorporating multiple net- at RT (20 °C). Depending on the concentration of the acryla-
works of physical crosslinks (sacrificial bonds) into a hydrogel mide, there exists two structural phases. A small concentra-
can lead to an increase not only of the self-healing properties, tion of acrylamide resulted in an isotropic structural phase,
but also (simultaneously) of the mechanical properties. A fully and a larger concentration produced an anisotropic structural
physically crosslinked interpenetrating polymer network has phase. Gelation occurred via hydrophobic interactions of the
been developed that utilizes a hydrogen bonded agar network bilayers and additional hydrogen bonding between polymer
and a hydrophobic-associated poly(acrylamide) network.[135] chains and the bilayer surfaces. The reversible hydrophobic
The second network’s ability to dissipate energy and with- interactions of the bilayers are utilized as the self-recovery
stand stress by sacrificial bonds (breakage and reformation mechanism, while the adsorption and the large extensibility
of the hydrophobic interactions) results in the large values of of the PAAm chains sustain very large deformations. The
toughness (650 J m−2), self-recovery (66% of tensile modulus strength of these hydrogels is a result of the rupture of the
in 120 min) and self-healing (40% tensile stress in 120 min) hydrophobic bonds between the bilayers that serve to dissi-
at RT (20 °C). The hydrogels exhibited excellent mechanical pate mechanical energy.[52]
strength and toughness comparable to chemically crosslinked Ionic–covalent-entanglement (ICE) network hydrogels are a
or hybrid-crosslinked gels. Rapid self-recovery of stiffness specific type of IPN. ICEs exhibit enhanced mechanical proper-
(60%) and toughness (40%) was achieved within 2 min. How- ties and consist of a tough and self-recovering IPN of an iono-
ever, full recovery of the mechanical characteristics was not tropic polymer network and a chemically crosslinkable polymer
achieved autonomously (i.e., without an external stimulus). To network. An ICE of ionically crosslinked gellan gum and cova-
achieve complete recovery, heat treatment was required.[135] A lently crosslinked poly(acrylamide) has been shown to recover
self-healing and shape-memory covalent poly(ethylene glycol) 53 ± 4% of its energy dissipation (hysteresis) of the first load
(PEG) hydrogel was developed by the incorporation of a physi- and almost completely recover from subsequent cycles at 21 °C.
cally crosslinked poly(vinyl alcohol) (PVA) network.[136] Exten- The recovery behavior is attributed solely to the reversible inter-
sive hydrogen bonding associated with PVA crosslinking actions of the ionically crosslinked gellan-gum network.[3] Simi-
provided the reversible interactions involved in the self-healing larly, another ICE fully swollen hydrogel based on the ionically
that would not normally be exhibited by covalently crosslinked crosslinked gellan gum and covalently genipin-crosslinked
hydrogels. Self-healing was observed and a tensile self-healing gelatin was able to recover hysteresis partially during cyclic
efficiency of 68% was obtained after 48 h at RT (20 °C). It compression tests.[2] This hysteresis during the first loading/
is known that PVA mechanical properties are improved unloading cycle to constant stress (150 kPa) or constant strain
by increasing the number of freeze/thaw cycles. However, (50%) was 24 ± 2 kJ m−3 and reduced to 6 ± 2 kJ m−3 for the
increasing the number of freeze/thaw cycles from 0 to 3 was immediate subsequent cycle (25% recovery) (Figure 13). In
shown to weaken the self-healing efficiencies from 68% to contrast, after reswelling in simulated body fluid (SBF), the
≈10%. The concept of anisotropic self-healing was explored for hydrogel was able to recover 95 ± 2% and 82 ± 7% hysteresis
the first time. Oriented chains in the width direction (where the at 37 °C after reloading to either constant stress (150 kPa) or
chains are on the fracture surface plane) were shown to have constant strain (50%), respectively.[2]
greater self-healing efficiencies (≈13% compared to ≈9% after
48 h healing), likely due to more hydroxyl group interactions,
greater space between crystallites, and, subsequently, more 5. Conclusions and Recommendations
chain movement.[136]
Another rapid SELF mechanism was developed based on Self-healing hydrogels present many advantages compared to
the self-assembly of an ABA tri-block copolymer through conventional hydrogels, with extended life-times and mechan-
hydrogen bonding, and aromatic π–π stacking and quadru- ical performance due to the absence of (or decrease in) irrevers-
polar (edge to face) interactions.[21] This hydrogel, formed by ible damage. Although this field of study shows great promise,
the triblock copolymer poly[(N-isopropylacrylamide)-co-(N- it is not without its challenges. When considering applications
3,4-dihydroxyphenethyl acrylamide)]-block-poly(ethylene for SELF hydrogels, it is fundamental to examine both the self-
oxide)-block-poly[(N-isopropylacrylamide)-co-(N-3,4-dihydroxy- healing abilities in conjunction with the mechanical robustness.
phenethyl acrylamide)], exhibits a thermoresponsive sol–gel These two properties are generally in opposition. Adopting the
transition and forms a gel at room temperature (20 °C). How- approach of incorporating multiple reversible reactions appears
ever, self-recovery was shown to be completely autonomous to be an appropriate direction.
www.advmat.de
REVIEW
tions. As the field of self-healing hydrogels is
an emerging one, there does not seem to be a
standard set of measurements used uniformly
across the literature to quantify self-healing. In
Table 1–6, we have presented measurements
that have been performed on samples under
either tension, compression, or shear. How-
ever, with each technique, there are several
different parameters available to quantify self-
healing. The self-healing performance of the
different types of hydrogels reviewed in this
paper is illustrated in Figure 14 (in the style of
an Ashby plot), where the self-healing time is
Figure 13. Stress–strain curves for loading/unloading cycles 1 and 2 of typical ICE network
hydrogel (2.75% w/w) samples compressed to 50% after resting in air. b) Hysteresis of the plotted against self-healing efficiency. The data
second loading/unloading cycle of a typical ICE network hydrogel compressed to 50% strain is selected from Table 1–6, but is not exhaus-
after resting in air (diamonds) or immersion in SBF for 10 min (squares) after the initial tive, as many studies state that they have
loading/unloading cycle. Reproduced with permission.[2] Copyright 2014, The Royal Society demonstrated self-healing (usually through
of Chemistry. visual means), but do not report experimental
data. The lack of an adopted standard in dem-
In Table 1–6 we present our summary of current SELF hydro- onstrating and quantifying self-healing makes a comparison
gels including details regarding classification, SELF mechanisms, between studies difficult.
self-healing efficiencies and/or recoveries, mechanical, rheolog- In terms of self-healing time, hydrogels with SELF mecha-
ical, or other characteristics, and (if any) demonstrated applica- nisms involving hydrophobic bonding and multi-mechanism
Table 1. Self-healing mechanism, self-healing efficiency, recovery, mechanical properties, demonstrated applications, and predicted suitability for
3D/4D printing for self-healing chemical hydrogels.
Polymer/materials SELF Healing testa) Self-healing Self-recoverya) Mechanical Demonstrated Predicted Ref.
mechanisms efficiencya) [%] propertiesb) application 3D/4D
[%] printing
ability [Y/N]
3-Armed poly(ethylene Acylhydrazone 48 h, 25 °C, >50%, 48 h ((f), – Up to ≈104 kPa – Y [72]
oxide) (PEO) terminated and disulfide pH 3, 6, and 9 break stress and (l) and ≈650%
with dithiodipropionic exchange (acidic and basic strain) (m)
acid dihydrazide and hex- conditions), (a)
anedioic acid dihydrazide,
respectively
Triblock (ABA) of Disulfide 24 h, 25 °C, (a) – 100%, <10 s, 2180 Pa (l) – Y [73]
1,2-dithiolane-func- exchange ((i), 4 cycles of
tionalized trimethlyene γ = 1% and 800%,
carbonate monomers ƒ = 1 Hz)
(A) and PEO (B), and
3,6-dioxa-1,8-octanedithiol
Poly(ethylene glycol) Up to 72 h, RT – – 38.6 kPa and Antifoulingand Y [74]
methyl ether methac- (20 °C), (e) 23.7 kPa (n) antibacterial coat-
rylate (PEGMA), and ings on stainless
poly(N-hydroxyethyl steel substrates
acrylamide (HEAA) and
2-(methacryloyloxy)-ethyl
trimethylammonium
chloride (META)),
and crosslinker bis(2-
methacryloyl)-oxyethyl
disulfide (BMOD)
Oxidized sodium Schiff base 6 h, 25 °C, pH 7, 86 ± 3.4%, 12 h 100%, <10 s ((i), 6044 ± 224 Pa 3D cell encapsula- Y [66]
alginate (OSA), adipic (imine linkage) (a) and (c) and 90 ± 2.7%, 1 cycle of γ = 1%, (l), ≤≈35 kPa (n) tion and drug
acid dihydrazide and and acylhydra- 48 h (g, beam– 80%, 1%, 300%, and ≤≈60% (n) delivery
N-carboxylethyl chitosan zone exchange shaped test) 1%, 800%, and
1%, ω = 10 rad s−1)
www.advmat.de
REVIEW
Table 1. Continued
Polymer/materials SELF Healing testa) Self-healing Self-recoverya) Mechanical Demonstrated Predicted Ref.
mechanisms efficiencya) [%] propertiesb) application 3D/4D
[%] printing
ability [Y/N]
Telechelic difunctional Schiff base 2 h, RT (20 °C), ≈590 Pa, at 100%, <100 s, ≈1150 Pa (l) Controlled releases Y [75]
poly(ethylene glycol) reactions (b) 0 min healing 37 °C ((i), 2 cycles of biomolecules
(PEG), and chitosan or (imine-linkage) time and 1050 Pa of γ = 20% and
glycol chitosan after 10 min of 200%, ƒ = 1 Hz)
healing, and
≈1150 Pa for
original sample
(h)
12 h, RT – 100%, < 10 s, ∼0.8 kPa at 25 °C Neural tissue Y [76]
(20 °C), (b) 37 °C (i, 3 cycles of and ∼1.5 kPa at engineering, 3D
γ = 1% and 300%, 37 °C (l) cell culture (CC),
ƒ = 1 Hz) and injection cell
therapy
15 min (b), ≈390 Pa at 0 min 100%, < 10 s ≈2 kPa (l) Tissue engineering Y [77]
30 min (c), RT healing time and ((i), 2.5 cycles of (TE), 3D CC,
(20 °C) ≈2000 Pa for γ = 1% and 200%, and injection cell
original sample ω = 6.3 rad s−1) therapy
(h)
Acrylamide modified 1–3 h, RT – 100%, < 10 s, ≈570 Pa (l) – N [78]
chitin and oxidized (20 °C), pH 7.4, 25 °C (i, 2 cycles of
alginate pH 10, (a), (b), γ = 1% and 200%,
(d), and (e) ƒ = 1 Hz)
Chondroitin sulfate 2 h, RT (20 °C), – – ≈103 Pa (l) TE, 3D CC, and Y [79]
multiple aldehyde and moisture, (a) injection cell
N-succinyl-chitosan and (e) therapy
Copolymer of 2-acrylami- Boronic ester 1 h, RT (20 °C), – 100%, <50 s, 25 °C ≈1 kPa and – Y [39]
dophenylboronic acid and exchange pH 4, pH 7, (a) ((j), ramp strain ≈350 kPa (l),
N,N′-dimethylacrylamide to 400% then respectively
(DMA) crosslinked with retraction to lesser
either poly(vinyl alcohol) strain in LVE)
(PVA) or copolymer of
DMA and dopamine
acrylamide (DOPAA)
3,6-dioxa- 2 min–4 days, ≈100%, 3 days – ≈1.4 MPa (m) – Y [40]
1,8-octanedithiol, RT (20 °C), (a) ((f) stress at
pentaerythritol tetrakis(3- break) and
mercaptopropionate) ≈85% ((f)
and 4-((Allyloxy)methyl)- elongation at
2-(4-vinylphenyl)-1,3,2- break)
dioxaborolane
N,N′-dimethylacrylamide Oxime exchange 2 h, RT (20 °C), – 100%, <17 s, 25 °C 102 kPa (l) – Y [80]
(DMA) and diacetone acryl- pH 7, (a) ((j), strain sweep test
amide (DAA) copolymer of 0.1–1000% then
crosslinked with γ = 50% strain,
O,O′-1,3-ççpropanediyl- ω = 10 rad s−1)
bishydroxylamine
dihydrochloride
a)Conditions and type: a) pieces of cut hydrogel rejoined, b) a hole punched from center of hydrogel, c) hydrogel injected after gelation, d) pieces of separately prepared
hydrogels joined, e) microscopy of cracks/scratches, f) tensile stress-strain curves, g) compression stress–strain curves, h) rheology test tracking storage modulus G′ [Pa],
i) alternative step strain deformation, or j) single strain deformation (tracking storage modulus G′, Pa or as stated), k) cyclic mechanical tests; b)Mechanical properties:
l) storage modulus G′ [Pa], m) tensile stress–strain curves or n) compressive stress–strain curves, o) energy dissipated (hysteresis), p) fracture energy.
www.advmat.de
REVIEW
Table 2. Self–healing mechanism, self–healing efficiency, recovery, mechanical properties, demonstrated applications, and predicted suitability for
3D/4D printing for self–healing physical hydrogels.
Polymer/materials SELF Healing testa) Self–healing Self–recoverya) Mechanical Demonstrated Predicted Ref.
mechanisms efficiencya) [%] [%] propertiesb) application 3D/4D printing
ability [Y/N]
PEG terminated by Ureidopy- Hydrogen – – ≈100%, min, 24 kPa (l) Catheter- Y [81]
rimidinone (Upy) (with urea bonding 37 °C ((i), 4.5 injection drug
functionality) cycles of delivery
γ = 1% or 100%,
ω = 1 rad s−1)
2-(N′-methacryloyloxyethyl- 25 ± 1 °C, (c) – – ≈102 Pa (l) – Y [44]
ureido)-6-(1-adamantyl)-
4[1H]-pyrimidinone and
N,N′-dimethylacrylamide
copolymer
Upy-functionalized dextran minutes, (a), – 100%, seconds, 700 Pa (l) TE, CC, and Y [14]
(c), and (d), RT RT (20 °C) injection cell
(20 °C) ((i), 3 cycles of therapy
σ = 0.1 Pa and
100 Pa,
ω = 1 rad s−1)
2-(Dimethylamino)-ethyl 5 min at RT – – – N [82,83]
methacrylate (DMAEMA) and (20 °C), (a) or
2-(3-(6-methyl-4-oxo-1,4-dihy- 2 min, (e),
dropyrimidin-2-yl) ureido)ethyl pH 7–8
methacrylate (SCMHBMA) (and
nitrobenzyl-caged SCHHBMA)
copolymer
Poly(vinyl alcohol) (PVA) 12 h, RT ≈72%, 48 h ((f), – ≈280 kPa (m) – N [47]
(20 °C), (a) stress at break)
PVA, chitosan, and 1 h (b) – – – CC and con- Y [84]
glutaraldehyde trolled drug
release
Acrylic acid, acrylamide, and 12 h (a) and – – 106 Pa (l) Water N [85]
glycogen 70 min (e), purification
neutral pH, RT
(20 °C)
Oligomeric poly(pyridinium-1,4- – – 100%, 220 min, 102 Pa (l) – Y [86]
diyl-iminocarbonyl-1,4-phenyle- 25 °C ((j),
nemethylene chloride) γ = 0.5% for
20 min then
γ˙ = 1000 s−1 for
30 min,
ω = 2 rad s−1)
DNA-grafted polypeptide and Immediate, (c), 100%, 5 min, 100%, imme- ≈275 Pa (l) – Y [87]
“X”-shaped DNA linker (d), RT (20 °C) 25 °C (h) diate, 25 °C ((i),
1.5 cycles of
σ = 0.7 Pa and
1000 Pa)
Poly(allylamine hydrochloride) Ionic – – 100%, ≈35 min, ≈400 kPa (l) – Y [88]
crosslinked with pyrophosphate (0.1−200%
or tripolyphosphate, respectively strain sweep
then γ = 0.4%,
ω = 1 rad s−1)
Carboxybetaine acrylamide 0 min, (a), RT 90%, immedi- 100%, 100 s, ≈62 kPa stress Cell adhesion Y [42]
(N,N′-methylenebis(acrylamide) (20 °C) ately, RT ((f), 25 °C ((i), 2.5 and ≈24 kPa and culture
crosslinked) stress and cycles of γ = 1% modulus m)
modulus) and 1000%) and ≈100 kPa
modulus (n)
www.advmat.de
REVIEW
Table 2. Continued
ability [Y/N]
β-cyclodextrin-functionalized Supra- 0 min–24 h, RT 99% and 74%, – ≤680 kPa – N [45]
poly(acrylamide) and N-adaman- molecular (20 °C), (a) respectively, 24 h and 0.33 kPa,
tane-1-yl-acrylamide copolymer ((g), wedged- respectively (l)
or α-cyclodextrin-functionalized shape strain
poly(acrylamide) n-butyl acrylate compression)
copolymer
β-cyclodextrin- and adamantine- – – – – Delivery of Y [89]
functionalized hyaluronic acid therapeutic
biomolecules for
chronic kidney
disease
– – 100%, <30 s, 103 Pa (l) Vehicle for Y [90]
25 °C ((i), 3.5 delivery of
cycles of therapeutic
γ = 0.5% and biomolecules
250%, f = 10 Hz)
– – – – 3D bioprinting Y [92]
β-cyclodextrin and adamantane 37 °C – ≥95%, 3 s, 37 °C 103 Pa (l) Protease-medi- Y [91]
bound by peptide tether to ((i), 3.5 cycles ated degradation
hyaluronic acid of γ = 0.5% and for controlled
250%, f = 10 Hz) drug delivery
Cholic-acid- and <1 min, RT – 97%, <30 s, ≤217 Pa (l) – Y [68]
β-cyclodextrin-functionalized (20 °C), (a) 25 °C ((i),
N,N′-dimethylacrylamide 2.5 cycles of
γ = 10% and
1000%)
β-cyclodextrin- and 1 min–1 h, RT – – >3000 Pa (l) – Y [93]
α-bromonaphthalene- (20 °C), (a)
functionalized acrylamide
β-cyclodextrin- and 1–60 min, RT ≈100%, 1 h, – 1300 Pa (l) – Y [94]
α-bromonaphthalene- (20 °C), (a) RT (h)
functionalized acrylamide with
gold nanoparticles modified with
6-thio-β-cyclodextrin
Poly(ethylene glycol) methyl – – 100%, 5 s, 37 °C ≈10 kPa (l) CC Y [95]
ether methacrylate (PEGMA)- ((I), 4.5 cycles of
grafted lignin hyperbranched γ = 0.01% and
copolymers and α-cyclodextrin. 10%)
β-cyclodextrin- and ferrocene- 24 h, RT – – 176 Pa (l) – Y [96]
functionalized poly(acrylic acid), (20 °C), (a)
respectively
Poly(N,N-dimethylacrylamide- – – 100%, imme- ≈103 Pa (l) CC Y [97]
r-glycidol methacrylate- diate ((I), 3.5
β-cyclodextrin) and cycles of
poly(N,N-dimethylacrylamide- γ = 0.1% and
r-2-hydroxyethylmethacrylate-fer- 100%)
rocene)
β-cyclodextrin-, adamantine-, 2 h, RT (20 °C), 68%, 72 h, – ≤20 kPa – Y [98]
and ferrocene-functionalized wet circum- RT (20 °C) modulus (m)
poly(N-isopropylacrylamide) stance (a) ((g), adhesion
strength (stress)
from tensile
test)
www.advmat.de
REVIEW
Table 2. Continued
ability [Y/N]
Cholesterol (Chol)-modified 1 min (a) and – ≈100%, <200 s, Up to 46 kPa In vitro degrada- Y [99]
triblock poly(L-glutamic 5 min (e), RT 25 °C ((i), 4 (n) tion, cytocom-
acid)-block-poly(ethylene glycol)- (20 °C) cycles of patability, and
block-poly(L-glutamic acid) γ = 0.1% and multilayer struc-
((PLGA-b-PEG-b-PLGA)-g-Chol) 500%, ω = 1.0 tures for use in
and β-cyclodextrin (β-CD)- rad s−1) hybrid tissue
modified poly(L-glutamic acid) regeneration
(PLGA-g-β-CD)
Catechol-functionalized chitosan – – 100%, 100 s, 800 Pa (l) and – Y [100]
and Fe3+ RT (20 °C) ((I), 5.1 × 103 J m−3
pH 5 and 7, 2.5 (o)
cycles of γ = 1%
and 1000%)
Acrylamide and octyl phenol Hydrophobic 6 days, RT – 100%, 15 min, ≤210 kPa and – Y [101]
polyethoxy ether acrylate (20 °C), “wet 25 °C ((k), ≈2750% (m)
copolymer, and sodium dodecyl conditions”, (a) tensile force
sulfate (SDS) as surfactant after 4 cycles of
stretching)
3 days, RT ≈40%, 3 days, ≈100%, ≈75 ≤210 kPa and – N [102]
(20 °C), “wet 25 °C ((f), stress min, 25 °C ((j), ≈1700% (m)
conditions”, (a) at break) and 1000% strain
≈70%, 3 days then recovery
((f), strain at after release)
break)
Acrylamide and stearyl methac- 20 °C, (a) ≈100%, few sec- – ca.103 Pa (k) – N [64]
rylate (C18) copolymer with SDS onds ((f), strain and 3600 ±
and NaCl at break ratios 630% (m)
of original and
healed samples
3600 ± 630 and
3580 ± 520%,
respectively)
24 °C, 10 min, 100%, 20 min, 100%, 2 min, <1700% (m) – N [70]
(a) 24 °C ((f), elon- 24 °C ((k)
gation at break 3 cycles of
ratios) compression
of constant
crossover speed
of 5 mm min−1 to
maximum load of
5 N then imme-
diate retraction
to zero load)
Acrylamide and n-alkyl (meth)- – 29, 34, and 20% 100%, <2 min, ≈10 kPa – Y [103]
acrylates (C12–22) copolymers for acrylates of 25 ± 0.5 °C modulus,
with SDS and NaCl C16, C18, and ((k), 3 cycles of 15–60 kPa,
C22, respectively, compression 10–15% strain
and 36, 49, 71, of constant at break (m)
and 88% (meth- crosshead speed
acrylates of C12, of 5 mm min−1
C16, C17.3, and to a maximum
C18, respectively, load of 5 N
30 min, 25 ± 0.5 then immediate
°C ((f), elonga- retraction to
tion at break zero load)
ratios)
www.advmat.de
REVIEW
Table 2. Continued
ability [Y/N]
Acrylamide and C18 copolymer 3 min, RT 98%, 60 min, 100%, seconds, 103 kPa (l), – Y [104]
with cetyltrimethylammonium (20 °C), (a) 35 °C ((f), 35 °C ((i), 4 6–10 kPa and
bromide (CTAB), SDS, and NaCl modulus) cycles of γ = 0.01 1800–5000%
rad s−1 of 200 s (m)
and strain-sweep
of γ = 0.01–4
rad s−1)
Poly(N-isopropylacrylamide), 30 min, 24 °C, 100%, ≈100%, 5 min, Up to 20 ± 2 – Y [105]
C18, CTAB and NaBr (a) 30 min for ≤10% 24 °C ((k), kPa modulus
monomer con- hysteresis from (m)
centration, 24 °C cyclic compres-
((f), modulus) sion of constant
crosshead speed
of 5 mm min−1
to a maximum
load of 90% the
immeiate retrac-
tion to zero
load).
Nano-amyloid fibrils – – 100%, seconds, – Cell adhesion Y [106]
25 °C ((i), 4 and 2D/3D
cycles of CC, neuronal
γ = 0.5% and differentiation
100%,
ω = 10 rad s−1)
a)
Conditions and type: a) pieces of cut hydrogel rejoined, b) a hole punched from center of hydrogel, c) hydrogel injected after gelation, d) pieces of separately prepared
hydrogels joined, e) microscopy of cracks/scratches, f) tensile stress–strain curves, g) compression stress–strain curves, h) rheology test tracking storage modulus G′ [Pa],
i) alternative step strain deformation, or j) single strain deformation (tracking storage modulus G′, Pa or as stated), k) cyclic mechanical tests; b) Mechanical properties:
3D/4D printing for self-healing nanocomposite hydrogels.
Polymer/materials SELF mechanisms Healing testa) Self-healing Self-recoverya) Mechanical Demonstrated Predicted 3D/4D Ref.
efficiencya) [%] propertiesb) application printing ability
[%] [Y/N]
Poly(vinyl alcohol) function- Supramolecular 10–30 s, RT – 100%, immediate, 14.3 kPa (l), – N [109]
alized with methyl viologen, guest–host (20 °C), (a) 25 °C ((i) 10
cellulose nanocrystal (CNC) cycles of
colloidal rods containing γ = 0.05%,
copolymer grafts of 120 s and
protonated dimethylamino- γ = 150%, 30 s)
ethyl methacrylate and
nephthyl methacrylate, and
cucurbit[8]uril
Nanofibrillated cellulose Hydrogen (a), RT (20 °C) 29.7 kPa for - ≤74.0 kPa – N [110]
(NFC), poly(vinyl alcohol) bonding healed (30 m) modulus and
(PVA), and borax and 31.1 kPa for 29.0 kPa
pristine sample, maximum stress
30 °C ((g), (n)
modulus)
Poly(acrylamide) and gra- 20 s at 4 °C and 88%, 24 h, - 0.35 MPa and – N [114]
phene peroxide 24 h at 30 °C, (a) 30 °C ((f), 4900% (m), and
and (d) fracture stress), 900 J m−2 (p)
92% (breaking
strain) and
100% (h)
www.advmat.de
REVIEW
Table 3. Continued
[%] [Y/N]
Poly(acrylamide), stearyl Hydrogen 3 days, in a wet ≤53% (f, fracture ≤51% ((k), hys- 243 kPa and Reusable absor- N [113]
methacrylate, sodium bonding and cabinet, (a) stress) teresis from 4.5 ≤1990% (m), bents for water
dodecyl benzene sulfonate, hydrophobic cycles of tensile and 263 kJ m−3 purification
and graphene oxide elongation to (o)
1000% strain)
Poly(acrylic acid), graphene Hydrogen 48 h, 45 °C, (a) ≈60 and ≈80%, 86.8%, 48 h, ≈860 kPa (m) – Y [115]
oxide, and Fe3+ bonding and 48 h, 25 °C 25 °C ((k), hyster-
ionic ((f), stress esis from tension
and strain, tests)
respectively)
Poly(N,N′- Hydrogen 48 h, 25 °C, (d) – – – – N [116]
dimethylacrylamide) bonding
(PDMAA) or poly(N-iso-
propylacrylamide) (PNIPA),
crosslinked with exfoliated
hectorite nanoplatelets
Poly(acrylamide) and 7 days, 25 °C, <1800% for 100%, 5 days, 11 800% and – N [117]
exfoliated montmorillonite (a) sample healed 25 °C ((k), 100–180 kPa
nanoplatelets for 7 days, RT γ = 8000% then (m)
(20 °C) and retraction to zero
11 800% original displacement for
samples ((f), 5 days then
fracture strain) γ = 8000%)
Poly(vinylpyrrolidone) Hydrogen 0–3 h, RT – – 210 Pa (l) Sequester and N [121]
(PVP) and aminopropyl- bonding and (20 °C), pH release of drugs
functionalized magnesium electrostatic 4–11, (a) and enzymes
phyllosilicate exfoliated adsorption
organoclay
Sodium poly(acrylate), < few mins, RT – – 550–600 kPa and – Y [118]
exfoliated montmorillonite (20 °C), (a) 55–100% (n)
nanoplatelets, and meth-
ylguanidine-functionalized
xylose
Hyaluronic acid, Electrostatic – - 100%, 20 s, 25 °C ≈0.5 kPa (l) – Y [111]
carboxymethylcellulose interaction ((j), viscosity after
poly(ethylene glycol)- shear rate of
block-poly(lactic acid) 100 s−1 then
nanoparticles, and cetyltri- 0.1 s−1)
methylammonium bromide
(CTAB).
Cellulose nanowhiskers, Hydrophobic 60 min, RT 100%, 60 min, – 1.338 MPa and – N [112]
acrylamide, stearyl meth- (20 °C), (a) (f) 2500% (m), and
acrylate, and sodium dodecy- 2.835 MPa (n)
lsulfate (SDS)
Exfoliated montmorillonite Coordination – – 70%, 600 s, 6 kPa (l) Removal of Y [119]
clay sheets coated with bonding pH 7, 23 °C ((i), an organic
poly(dopamine) and ferric 3.5 cycles of pollutant,
ions γ = 0.1% and Rhodamine 6G,
γ = 100%, from water
ω = 6.0 rad s−1)
Sodium polyacrylate, exfoli- Ionic RT (20 °C), (a) – 100%, immediate, 0.5 MPa (l) Transport/pres- Y [120]
ated clay nanosheets, and 20 °C (i, 3.5 cycles ervation of bio-
guanidinium functionalized of γ = 0.1% and logical activities
dendritic macromolecules γ = 100%, ω = 6.0 (myoglobin)
rad s−1)
www.advmat.de
REVIEW
Table 3. Continued
[%] [Y/N]
Poly(acrylic acid), vinyl Ionic and 4–70 °C, (a) ≈30%, 48 h, 25 °C – ≤1.0 MPa, – N [122]
hybrid silica nanoparticles, hydrogen ((f), strength and ≈2350% (m)
and ferric ions bonding elongation at
break ratio)
Terpyridine-end-capped Coordina- – – >90%, 300 s, 102–103 Pa (l) – N [123]
poly(ethylene glycol), col- tion bonding 23.5 °C ((i), 3.5
loidal silica nanoparticles, and hydrogen cycles of γ = 5%
and CoCl2 bonding for 300 s, f = 10
Hz, rotation at
10 s−1 for 120 s)
Tribolck polymer of N,N- Ionic – – 100%, 100 s, - – N [124]
dimethylaminoethylmeth- 25 °C ((i), 3.5 cycles
acrylate and ethylene oxide, of γ = 0.1% or 80%)
Pluronic F127, LAPONITE,
CO2
a)Conditions and type: a) pieces of cut hydrogel rejoined, b) a hole punched from center of hydrogel, c) hydrogel injected after gelation, d) pieces of separately prepared
3D/4D printing for self-healing physical multi-mechanism single-network hydrogels.
Polymer/materials SELF Healing testa) Self-healing Self-recoverya) Mechanical Demonstrated Predicted 3D/4D Ref.
mechanisms efficiencya) [%] propertiesb) application printing ability
[%] [Y/N]
Poly(acrylic acid), Hydrophobic minutes, 100%, 30 min, ≈100%, 5 min, 0.7–1.7 MPa and – Y [125]
stearyl methacrylate and Ionic 25 °C, (a) 25 °C ((f), mod- 25 °C ((k), hyster- 800–900% at
(C18), in aqueous solu- ulus) and 20–30%, esis from cyclic of break (m)
tions of cetyltrimethyl- 30 min ((f), compression of
ammonium bromide fracture stress) constant crosshead
(CTAB) and NaBr speed of
5 mm min−1 to a
maximum load of
92% then imme-
diate retraction to
zero load)
Poly(acrylic acid), Hydrophobic 30 min, 23 ± ≤60%, 30 min, 100%, 10 min, 6–53 kPa – N [126]
stearyl methacrylate and hydrogen 2 °C, (a) 23 ± 2 °C ((f), 23 ± 2 °C ((i), 5 modulus,
(C18), SDS, and NaCl bonding fracture stress) cycles of increasing 41–173 kPa frac-
elongation) ture stress and
1800–5000%
(m)
Poly(N,N-dimethyl- 10 min, 24 °C, 100%, 2 min, 100%, 7 min, ≈103 Pa (k), – Y [65]
acrylamide), C18, SDS, (a) 24 °C ((f), mod- 24 °C ((k), hyster- 4200 ± 200%
and NaCl ulus) and 20 min esis from cyclic (m), 2.4 ± 0.2
((f) fracture; stress compression and MPa and 96%
and elongation elongation tests) (n), 11 ± 2 kPa
ratios at break) modulus (m
and n)
Acrylamide and Ionic – – 100%, <9 s, 103 Pa (l) – Y [41]
3-((2-(methacryloyloxy)- 25 °C ((i), 3.5
ethyl) cycles of γ = 1%
dimethylammonio)- and γ = 1400%)
propane-1-sulfonate
(DMAPS)
www.advmat.de
REVIEW
Table 4. Continued
Polymer/materials SELF Healing testa) Self-healing Self-recoverya) Mechanical Demonstrated Predicted 3D/4D Ref.
mechanisms efficiencya) [%] propertiesb) application printing ability
[%] [Y/N]
Elastin-like polypeptide Metal, coordina- 1 min, RT ≈90%, ≈1 min, – ≈1 MPa (l) and – Y [67]
(ELP) of aminoacid tion, hydro- (20 °C), (a) RT (20 °C) ((g), ≈0.8–1.0 MPa
sequence MG-(VPGVG)60 phobic, and van stress) modulus (n)
(VPGAGVPGGG)30 der Waals
HEDGHWDGSEHGY-G
and Zn2+
Furylamine and adipic- Acylhydrazone 3 h, ambient ≈100%, ambient – 18 kPa (l) Adhesion to N [127]
dihydrazide-function- temperature temperature cartilage
alized hyaluronic acid, (20 °C), (a) (20 °C) ((g),
and furylamine-func- modulus)
tionalized and oxidized
hyaluronic acid
a)
3D/4D printing for self-healing hybrid-network hydrogels.
Polymer/materials SELF mechanisms Healing testa) Self-healing Self-recoverya) [%] Mechanical Demonstrated Predicted 3D/4D Ref.
[Y/N]
Poly(acrylamide), N,N′- Hydrophobic – – 100%, 15 min (k, ≈600 kPa, ≈22 m m−1 – N [57]
methylenebis(acrylamide) hysteresis from (m), ≈55 kJ m−3 (o)
and poly(dodecyl glyceryl cyclic tensile tests)
itaconate)
Acrylamide, stearyl meth- 24 ± 1 °C, (a) ≈80%, 60 min, ≈100%, 14 min, 25 kPa (l), 4.1 ± 0.2 – N [128]
acrylate (C18) and N,N′- 24 ± 1 °C ((f), 24 ± 1 °C ((k), at break ratio (m),
methylenebis(acrylamide), modulus) cyclic hysteresis 8.1 ± 1 MPa stress
SDS and NaCl from tensile tests) and 38 ± 5 kPa
modulus (n)
Poly(acrylic acid) (PAAc), Ionic 6 h, RT 80%, 6 h, RT ≈100%, immediate ≈560% (healed – Y [129]
N,N′-methylenebisacryl- (20 °C), (a) (20 °C) ((f), ((i), 2 cycles of sample) (m)
amide and cerium ions and 12 h (e) elongation at γ = 10% and
break) γ = 600%)
Poly(acrylamide), N,N′- – – “somewhat”, 156 kPa and 23 cm – Y [130]
methylenebis(acrylamide), 1 day, 20 °C ((k), stress and stretch at
alginate, and CaSO4.2H2O hysteresis from rupture, respectively
cyclic tensile tests) (m), and
8700 J m−2 (p)
Poly(acrylic acid), N,N′- 6 h, RT 88%, RT (20 °C) 100%, immediate, ≈2.7 kPa (l) and – Y [43]
methylenebis(acrylamide), (20 °C), (a) ((f), elongation 25 ± 0.1 °C ((i), 2.5 ≈200% (m)
and FeCl3 and (e) at break) cycles of γ = 5%
and γ = 400%, ω =
1 rad s−1)
Poly(ethylene glycol) Hydrogen 10 min, RT 80.2–86.6%, – 134.0–382.0 kPa and – Y [131]
methacrylate end-capped bonding (20 °C), (a) 10 min, RT 1800–2000% (m)
urethane ether and and (e) (20 °C) ((f),
2-(3-(6-methyl-4-oxo-1,4-di- strength)
hydropyrimidin-2-yl)ureido)-
ethyl methacrylate
www.advmat.de
REVIEW
Table 5. Continued
Polymer/materials SELF mechanisms Healing testa) Self-healing Self-recoverya) [%] Mechanical Demonstrated Predicted 3D/4D Ref.
[Y/N]
Suckerin-19 and – – 100%, <30 s, ≈40–500 Pa (l) CC N [132]
tris(bipyridine)- 20 °C (j, amplitude
ruthenium(II) chloride strain sweep then
recovery at γ = 2%)
Carboxymethyl chitosan <1 h, “mild 66% and 85%, – ≤101% at break and – N [133]
and acryloyl-6-aminocaproic conditions”, 23 °C ((f), 850 kPa (m)
acid (a) stress and strain
respectively)
Lauryl-g-peptide(VVAGKK- Hydrogen bonding – – ≈20–30%, 10 min, – – N [134]
Am amphiphile and and hydrophobic 4 °C, pH 7.5 ((j),
glutaraldehyde amplitude strain
sweep up to γ =
1000% then recovery
at γ = 0.01%)
a)
3D/4D printing for self-healing interpenetrating polymer network (IPN) hydrogels.
[%] [Y/N]
Gelatin, genapin, gellan gum, and Ionic – – 24 ± 2 kJ m−3 (first 1.1 ± 0.2 MPa at – Y [2]
CaCl2 cycle) and 6 ± fracture (n),
2 kJ m−3 (second 200 ± 40 kJ m−3
cycle), 37 °C, (o) and
immediate ((k), 126 ± 6 kJ m−2
hysteresis from (p)
2 cyclic compres-
sion tests)
Poly(acrylamide), N,N′- – – 53 ± 4% (first cycle) 8 kPa (l), 216 ± – Y [3]
methylenebis(acrylamide), gellan and 90 ± 9%, 31 kPa at failure
gum, and CaCl2 21 °C (subsequent (n) and
cycles), 80 min ((k), 44 ± 6 kJ m−3 (o)
hysteresis from cyclic
compression tests)
Acrylamide, stearyl methacrylate Ionic, hydro- 24 h, RT ≈40%, 24 h, ≈66% and ≈52%, 106 kPa – Y [135]
(C18), and agar in aqueous soluion phobic, and (20 °C), (a) RT (20 °C) 120 min, RT modulus (m),
of SDS and NaCl hydrogen (f, stress) (20 °C) ((k), mod- 0.267 MPa at
bonding ulus and hysteresis, break (m) and
respectively, from ≈650 J m−2 (p)
2 cycles of tensile
loadings)
Poly(ethylene glycol) and poly(vinyl Hydrogen – 68%, 48 h, RT – 0.63 MPa (m) – N [136]
alcohol) bonding (20 °C) ((f),
fracture stress)
ABA triblock copolymer of Hydrogen Immediate, – 100%, <6 s, 37 °C 103 Pa (l) Cytotox- Y [21]
poly[(N-isopropylacrylamide)- bonding and 37 °C, (a) ((i), 4.5 cycles of icity and
co-(N-3,4-dihydroxyphenethyl aromatic γ = 1% or anti-fouling
acrylamide)]-block-poly- interactions γ = 500%) assays
(ethylene oxide)-block-poly[(N-
isopropylacrylamide)-co-(N-3,4-di-
hydroxyphenethyl acrylamide)]
www.advmat.de
REVIEW
Table 6. Continued
[%] [Y/N]
Poly(acrylamide), poly(dodecyl Hydrophobic – – >90%, ≈30 min, 0.06 MPa mod- – Y [52]
glyceryl itaconate), and SDS RT (20 °C) ((k), 7 ulus, 0.04–0.18
cycles of elongation MPa fracture
to 0.5 mm mm−1 stress and
and immediate fracture strain of
retraction to 0 with 2–22 (m)
≤30 min waiting)
a)
are the fastest (30 min) and can display a large range of self- deformation after loading–unloading cycles.[138] This model was
healing efficiencies (20–100%). In contrast, mechanisms expanded to capture the effect of physical crosslinks breaking
involving nanocomposites, hydrogen bonding, hybrid net- and reattaching in a chemically crosslinked polymer network.
works, and supramolecular bonding are slower to self-heal (up The rate-dependent mechanical behavior and kinetics of
to several days), but almost always exhibit efficiencies of at least breaking and reattachment of temporal crosslinks were quanti-
50%. The general trend (apart from IPN and covalent bonding fied.[139] Other theories and simulations of autonomous SELF
gels) that emerges is that the self-healing time improves with mechanisms in published work are with regard to other poly-
self-healing efficiency. In other words, gels that have mecha- meric materials (not specific to hydrogels).[5,38] For example,
nisms that self-heal better also do it faster compared to gels that Rubinstein’s group has developed theory and simulations of
only partially self-heal. self-healing of unentangled polymer networks via the formation
The mechanical properties tested for and provided also of reversible bonds across a crack interface.[140] The work inves-
vary between studies and have been completed using different tigates the kinetics of self-healing and the authors expect their
parameters that make a comparison not straightforward. How- theory to be translatable to other polymeric systems. The devel-
ever, if we focus on a comparison of storage moduli; covalent opment of theory with the aid of simulation of SELF mecha-
bonding ranges from 100 Pa to 1.4 MPa, hydrogen bonding nisms specific to hydrogels should provide a strong foundation
ranges from 100 Pa to 280 kPa, ionic interactions range from for further growth in this field.
400 kPa to 680 kPa, supramolecular interactions range from SELF hydrogels possess great potential for extrusion-based
100 Pa to 3 kPa, and hydrophobic interactions range from 3D printing, which involves directing the material through a
800 Pa to 100 kPa (see Figure 15). With overlap, a basic correla- nozzle to be deposited layer upon layer.[16] Printing technologies
tion between the self-healing (and/or self-recovery) mechanism allow precise positioning and blending of materials that enable
and decreasing storage-modulus strength was found, such 3D control of the fabrication process. Furthermore, 3D-printing
that covalent bonding > ionic bonding > hydrogen bonding ≈ allows for the design and fabrication of materials with tailored
hydrophobic bonding > supramolecular interactions. Tough functionality, i.e., multiple materials can be utilized in the fab-
networks (with multiple crosslinks not all necessarily used in rication of components. Extrusion-based 3D printing of hydro-
SELF) exhibit storage moduli of 40 Pa to 25 kPa for hybrid net- gels requires consideration of the polymer rheology and gela-
works, 200 Pa to 15 kPa for (nano)composites, 100 Pa to 8 kPa tion mechanism. The polymer ink needs to be fluid enough to
for IPNs, and 100 Pa to 1 MPa for physical multi-mechanism pass though the nozzle but also needs to have enough structural
single networks, which are comparable to covalently crosslinked integrity when deposited to support subsequent layers. Prema-
SELF hydrogels. ture gelation must be avoided if a homogeneous 3D structure
The fracture mechanics of hydrogels are well understood is desired.[16] The reversible nature of the crosslinks enables
with various theories and simulations, and this has been the SELF hydrogels to exhibit shear-thinning properties.[92,141] SELF
basis for the development of tougher hydrogels.[56,130] However, hydrogels have the potential ability to be printed after gelation
the theories and simulations of autonomous SELF mechanisms and self-heal to form the desired homogeneous whole 3D struc-
in hydrogels are not complete. Hui and Long have devised a ture, circumventing the gelation limitations.
3D finite strain constitutive model to study the deformation 4D printing is emerging as an exciting technique in devel-
of a hydrogel with two types of crosslinks.[138] The model was oping new dynamic materials and devices. It involves 3D
based on the reversibility of physical bonds in a physical multi- printing a smart material or device that can change shape and/
mechanism single network. The model simulated uniaxial ten- or function over time.[142] This area of additive manufacturing
sile tests. The model addressed macroscopic softening (hard- is attracting a lot of attention with potential applications in self-
ening) behavior due to breaking (healing) of physical bonds, i.e. assembly materials (for building applications), self-disassembly
it showed that strain softening can be suppressed by slowing materials (for security applications), and bio-engineering
the loading rates, and was able to predict hysteresis and plastic (e.g., stents, living electrodes, and edible electronics).[24] Our
www.advmat.de
natural system.[24] In the previous example,

REVIEW
hard and soft structures were formed simul-

taneously. In some instances, soft hydrogels
may require bonding to preformed hard
surfaces. Hydrogels have been developed
that exhibit tough bonding to hard sur-
faces.[137,143] These tough adhesive hydrogels
have been shown to bond to several different
hard and nonporous materials, and were
used to form hydrogel electronic devices.
When the hydrogel is stretched, the flexible
components deform together, while the rigid
and hard components do not deform. To
establish a tough interface, first the hydrogel
must be tough and possess reversible sacri-
ficial crosslinks. Then interfacial adhesion is
achieved by covalent anchoring of the tough
polymer network to the hard surfaces. Under
deformation, the sacrificial bonds in the bulk
of the tough hydrogel break and dissipate
energy, while the interface remains cova-
lently anchored.[137,143] We envisage that the
gels identified in Table 1–6 will be utilized to
create complex interfacial structures between
hard and soft materials.
Combining hard and soft materials and
the fabrication method of 3D/4D-printing
has opened up many possible applications
for SELF healing hydrogels. For example, we
envisage that the development of SELF-hydro-
gels will play an integral part in the develop-
ment of materials for soft robotics. It is not
a new concept for hydrogels to be utilized
for soft robotics. Tough hydrogels have long
been identified as suitable soft and inexpen-
sive materials for soft robotics.[12] However,
SELF hydrogels will enable the development
of soft, deformable device components that
will be able to conform to complex environ-
ments, to regain shape and functionality after
Figure 14. Self-healing time as a function of self-healing efficiency according to the types of large deformations, and are able to self-heal
networks and the type of bonding utilized in the SELF hydrogel. a) Hydrogels that self-heal on (i.e., they can be used multiple times). The
time-scale of less than 1 h. b) Hydrogels that self-heal on time-scale of up to 72 h. Data were latter point is crucial, and has far-reaching
assembled from the values presented in Table 1–6. Note: self-healing efficiencies were obtained consequences, as indicated over a decade ago
from a mixture of methods.
by the polymer composite community.[144]
Much of this holds true for self-healing gels
predictions of the suitability of current SELF hydrogels for that are particularly useful “where it is not possible, or prac-
use in 3D/4D printing are presented in Table 1–6. These pre- tical to repair once the material has been put into use.”[144] A
dictions are based on the method of hydrogel formation (e.g., prime example of this is minimally invasive surgery soft robots,
type of polymerization and gelation time), suitability for reac- where hydrogels can serve as soft robotic actuators and as a
tive printing, injectability, and/or the SELF ability of the current soft body material with integrated tissue engineering scaffold
hydrogels. materials for repair or delivery of therapeutic agents.[145] Soft
Most animals contain interfaces between hard and soft mate- robotic (hydrogel) actuators have many other application areas,
rials that are extremely tough, e.g., the bonding of tendons to such as in producing complex soft motions for picking up and
bones. This is an area of research that is slowly being addressed packing delicate objects, or in creating a soft exoskeleton to
for interfacing soft hydrogel materials with hard materials. For assist the elderly and those with mobility impairments.[146] The
example, an artificial meniscus was 3D-printed with compo- latter is an example of an assisted health technology, aiming to
nents of varying degrees of hardness that mimicked both the merge the interface of the human body and machines, as well
complex shape and internal fiber-reinforced structure of the as implants and limb replacements.
www.advmat.de
REVIEW
[8] K. S. Toohey, N. R. Sottos, J. a. Lewis, J. S. Moore, S. R. White,
Nat. Mater. 2007, 6, 581.
[9] B. K. Ahn, D. W. Lee, J. N. Israelachvili, J. H. Waite, Nat. Mater.
2014, 13, 867.
[10] M. Krogsgaard, M. R. Hansen, H. Birkedal, J. Mater. Chem. B
2014, 2, 8292.
[11] M. Krogsgaard, M. A. Behrens, J. S. Pedersen, H. Birkedal, Bio-
macromolecules 2013, 14, 297.
[12] P. Calvert, Adv. Mater. 2009, 21, 743.
[13] E. Caló, V. V Khutoryanskiy, Eur. Polym. J. 2014, 65, 252.
[14] S. Hou, X. Wang, S. Park, X. Jin, P. X. Ma, Adv. Healthcare Mater.
2015, 4, 1491.
[15] U. Rottensteiner, B. Sarker, D. Heusinger, D. Dafinova, S. N. Rath,
J. P. Beier, U. Kneser, R. E. Horch, R. Detsch, A. R. Boccaccini,
A. Arkudas, Materials. 2014, 7, 1957.
Figure 15. Schematic showing the correlation between the storage mod- [16] D. M. Kirchmajer, R. GorkinIII, M. in het Panhuis, J. Mater. Chem.
ulus (G′), and the type of networks, and the type of bonding utilized in SELF B 2015, 3, 4105.
hydrogels. Data were assembled from the values presented in Table 1–6. [17] C. J. Ferris, K. G. Gilmore, G. G. Wallace, M. in het Panhuis, Appl.
Microbiol. Biotechnol. 2013, 97, 4243.
[18] C. J. Ferris, K. J. Gilmore, G. G. Wallace, M. in het Panhuis, Soft
Finally, the development of autonomous SELF hydrogels is Matter 2013, 9, 3705.
at its infancy (compared to stimuli-responsive self-healing) with [19] N. Kitamura, K. Yasuda, M. Ogawa, K. Arakaki, S. Kai, S. Onodera,
many new studies emerging every day. However, our review T. Kurokawa, J. P. Gong, Am. J. Sports Med. 2011, 39, 1160.
indicates that hydrogels that self-heal faster also do this better [20] S. Merino, C. Martin, K. Kostarelos, M. Prato, E. Vázquez, ACS
in comparison to gels displaying only partial self-healing. Our Nano 2015, 9, 4686.
recommodations include the adoption of standards in char- [21] L. Li, B. Yan, J. Yang, L. Chen, H. Zeng, Adv. Mater. 2015, 27, 1294.
[22] E. A. Appel, M. W. Tibbitt, M. J. Webber, B. A. Mattix, O. Veiseh,
acterizing efficiencies and reporting of mechanical properties
R. Langer, Nat. Commun. 2015, 6, 6295.
(either under tension, compression, or shear) of self-healing [23] A. Vashist, A. Vashist, Y. K. Gupta, S. Ahmad, J. Mater. Chem. B
hydrogels and the development of theory and simulations 2014, 2, 147.
of self-healing. The latter is of crucial importance to enhance [24] S. E. Bakarich, R. Gorkin, M. Spinks, ACS Appl. Mater. Interfaces
our understanding of these interesting soft materials and their 2014, 6, 15998.
potential applications. We are confident that the future shines [25] X. K. D. Hillewaere, F. E. Du Prez, Prog. Polym. Sci. 2015, 49–50,
bright for self-healing hydrogels, in particular in the area of soft 121.
robotics, i.e., soft actuators and wearable soft robotic skins (or [26] A. Phadke, C. Zhang, B. Arman, C.-C. C. Hsu, R. A. A. Mashelkar,
exoskeletons) for assisted health technologies. A. K. K. Lele, M. J. Tauber, G. Arya, S. Varghese, Proc. Natl. Acad.
Sci. USA 2012, 109, 10.
[27] T.-A. Asoh, W. Kawai, A. Kikuchi, Colloids Surf., B 2014, 123, 742.
[28] L. Hu, X. Cheng, A. Zhang, J. Mater. Sci. 2014, 50, 2239.
Acknowledgements [29] A. J. McConnell, C. S. Wood, P. P. Neelakandan, J. R. Nitschke,
Chem. Rev. 2015, 115, 7729.
The authors wish to acknowledge the financial support provided by the
[30] Z. Wei, J. H. Yang, J. Zhou, F. Xu, M. Zrínyi, P. H. Dussault,
University of Wollongong (UOW) and the Australian Research Council
Y. Osada, Y. M. Chen, Chem. Soc. Rev. 2014, 43, 8114.
(ARC) through its Center of Excellence program.
[31] Y. Jin, C. Yu, R. J. Denman, W. Zhang, Chem. Soc. Rev. 2013, 42,
6634.
Received: March 24, 2016 [32] Y. Yang, X. Ding, M. W. Urban, Prog. Polym. Sci. 2015, 49–50, 34.
Revised: June 3, 2016 [33] P. Michael, D. Döhler, W. H. Binder, Polymer 2015, 69, 216.
Published online: August 4, 2016 [34] V. K. Thakur, M. R. Kessler, Polymer 2015, 69, 369.
[35] N. Zhong, W. Post, Composites, Part A 2015, 69, 226.
[36] Y. Yang, M. W. Urban, Chem. Soc. Rev. 2013, 42, 7446.
[37] E. B. Murphy, F. Wudl, Prog. Polym. Sci. 2010, 35, 223.
[1] M. D. Hager, P. Greil, C. Leyens, S. van der Zwaag, U. S. Schubert, [38] D. Y. Wu, S. Meure, D. Solomon, Prog. Polym. Sci. 2008, 33, 479.
Adv. Mater. 2010, 22, 5424. [39] C. C. Deng, W. L. A. Brooks, K. A. Abboud, B. S. Sumerlin, ACS
[2] D. M. Kirchmajer, M. in het Panhuis, J. Mater. Chem. B 2014, 2, Macro Lett. 2015, 4, 220.
4694. [40] J. J. Cash, T. Kubo, A. P. Bapat, B. S. Sumerlin, Macromolecules
[3] S. E. Bakarich, G. C. Pidcock, P. Balding, L. Stevens, P. Calvert, 2015, 48, 2098.
M. in het Panhuis, Soft Matter 2012, 8, 9985. [41] H. Liu, C. Xiong, Z. Tao, Y. Fan, X. Tang, H. Yang, RSC Adv. 2015,
[4] A. B. W. Brochu, S. L. Craig, W. M. Reichert, J. Biomed. Mater. Res., 5, 33083.
Part A 2011, 96 A, 492. [42] T. Bai, S. Liu, F. Sun, A. Sinclair, L. Zhang, Q. Shao, S. Jiang, Bio-
[5] B. J. Blaiszik, S. L. B. Kramer, S. C. Olugebefola, J. S. Moore, materials 2014, 35, 3926.
N. R. Sottos, S. R. White, Annu. Rev. Mater. Res. 2010, 40, 179. [43] Z. Wei, J. He, T. Liang, H. Oh, J. Athas, Z. Tong, C. Wang, Z. Nie,
[6] S. D. Bergman, F. Wudl, J. Mater. Chem. 2008, 18, 41. Polym. Chem. 2013, 4, 4601.
[7] Y. Fang, C.-F. Wang, Z.-H. Zhang, H. Shao, S. Chen, Sci. Rep. 2013, [44] T. V Chirila, H. H. Lee, M. Oddon, M. M. L. Nieuwenhuizen,
3, 2811. I. Blakey, T. M. Nicholson, J. Appl. Polym. Sci. 2014, 131, 39932.
www.advmat.de
REVIEW
[45] T. Kakuta, Y. Takashima, M. Nakahata, M. Otsubo, H. Yamaguchi, P. A. Doevendans, J. P. G. Sluijter, E. W. Meijer, S. A. J. Chamuleau,
A. Harada, Adv. Mater. 2013, 25, 2849. P. Y. W. Dankers, Adv. Healthcare Mater. 2014, 3, 70.
[46] O. Okay, in Supramolecular Polymer Networks and Gels, Advances [82] J. Cui, A. del Campo, A. del Campo, Chem. Commun. 2012, 48,
in Polymer Science, (Ed: S. Seiffert), Springer International Pub- 9302.
lishing, Cham, Switzerland 2015, pp. 101–142. [83] J. Cui, D. Wang, K. Koynov, A. del Campo, ChemPhysChem 2013,
[47] H. Zhang, H. Xia, Y. Zhao, ACS Macro Lett. 2012, 1, 1233. 14, 2932.
[48] S. Naficy, H. R. Brown, J. M. Razal, G. M. Spinks, P. G. Whitten, [84] G. Chang, Y. Chen, Y. Li, S. Li, F. Huang, Y. Shen, A. Xie, Carbohydr.
Aust. J. Chem. 2011, 64, 1007. Polym. 2015, 122, 336.
[49] R. C. Manske, Fundamental Orthopedic Management for the [85] B. Vivek, E. Prasad, J. Phys. Chem. B 2015, 119, 4881.
Physical Therapist Assistant, Elsevier, St Louis, MO, USA, 2015. [86] S. K. Kundu, T. Matsunaga, M. Yoshida, M. Shibayama, J. Phys.
[50] N. K. Simha, C. S. Carlson, J. L. Lewis, J. Mater. Sci. Mater. Med. Chem. B 2008, 112, 11537.
2004, 15, 631. [87] C. Li, P. Chen, Y. Shao, X. Zhou, Y. Wu, Z. Yang, Z. Li, T. Weil,
[51] G. Bellucci, Rheumatology 2001, 40, 1337. D. Liu, Small 2015, 11, 1138.
[52] X. Li, T. Kurokawa, R. Takahashi, M. A. Haque, Y. Yue, T. Nakajima, [88] Y. Huang, P. G. Lawrence, Y. Lapitsky, Langmuir 2014, 30, 7771.
J. P. Gong, Macromolecules 2015, 48, 2277. [89] C. B. Rodell, R. Rai, S. Faubel, J. A. Burdick, D. E. Soranno, J. Con-
[53] J. P. Gong, Science 2014, 344, 161. trolled Release 2015, 206, 131.
[54] F. Luo, T. L. Sun, T. Nakajima, T. Kurokawa, Y. Zhao, K. Sato, [90] C. B. Rodell, A. L. Kaminski, J. A. Burdick, Biomacromolecules 2013,
A. Bin Ihsan, X. Li, H. Guo, J. P. Gong, Adv. Mater. 2015, 27, 2722. 14, 4125.
[55] F. Luo, T. L. Sun, T. Nakajima, T. Kurokawa, A. Bin Ihsan, X. Li, [91] C. B. Rodell, R. J. Wade, B. P. Purcell, N. N. Dusaj, J. A. Burdick,
H. Guo, J. P. Gong, ACS Macro Lett. 2015, 4, 961. ACS Biomater. Sci. Eng. 2015, 1, 277.
[56] J. P. Gong, Soft Matter 2010, 6, 2583. [92] C. B. Highley, C. B. Rodell, J. A. Burdick, Adv. Mater. 2015, 27,
[57] M. A. Haque, T. Kurokawa, G. Kamita, J. P. Gong, Macromolecules 5075.
2011, 44, 8916. [93] H. Chen, X. Ma, S. Wu, H. Tian, Angew. Chem. 2014, 126, 14373.
[58] R. E. Webber, C. Creton, H. R. Brown, J. P. Gong, Macromolecules [94] L. Chen, H. Chen, X. Yao, X. Ma, H. Tian, Chem.–Asian J. 2015, 10,
2007, 40, 2919. 2352.
[59] S. X. Zhao, Soft Matter 2014, 10, 672. [95] D. Kai, Z. W. Low, S. S. Liow, A. Abdul Karim, H. Ye, G. Jin, K. Li,
[60] E. Ducrot, Y. Chen, M. Bulters, R. P. Sijbesma, C. Creton, Science X. J. Loh, ACS Sustainable Chem. Eng. 2015, 3, 2160.
2014, 344, 186. [96] M. Nakahata, Y. Takashima, H. Yamaguchi, A. Harada, Nat.
[61] F. Luo, T. L. Sun, T. Nakajima, T. Kurokawa, Y. Zhao, A. Bin Ihsan, Commun. 2011, 2, 511.
H. L. Guo, X. F. Li, J. P. Gong, 2014. [97] L. Peng, H. Zhang, A. Feng, M. Huo, Z. Wang, J. Hu, W. Gao,
[62] C. W. Peak, J. J. Wilker, G. Schmidt, Colloid Polym. Sci. 2013, 291, J. Yuan, Polym. Chem. 2015, 6, 3652.
2031. [98] K. Miyamae, M. Nakahata, Y. Takashima, A. Harada, Angew. Chem.
[63] E. M. Ahmed, J. Adv. Res. 2013, 6, 105. 2015, 127, 9112.
[64] D. C. Tuncaboylu, M. Sari, W. Oppermann, O. Okay, Macromol- [99] G. Li, J. Wu, B. Wang, S. Yan, K. Zhang, J. Ding, J. Yin, Biomacro-
ecules 2011, 44, 4997. molecules 2015, 16, 3508.
[65] M. P. Algi, O. Okay, Eur. Polym. J. 2014, 59, 113. [100] P. S. Yavvari, A. Srivastava, J. Mater. Chem. B 2015, 3, 899.
[66] Z. Wei, J. H. Yang, Z. Q. Liu, F. Xu, J. X. Zhou, M. Zrínyi, Y. Osada, [101] G. Jiang, C. Liu, X. Liu, G. Zhang, M. Yang, F. Liu, Macromol.
Y. M. Chen, Adv. Funct. Mater. 2015, 25, 1352. Mater. Eng. 2009, 294, 815.
[67] A. Ghoorchian, J. R. Simon, B. Bharti, W. Han, X. Zhao, A. Chilkoti, [102] G. Jiang, C. Liu, X. Liu, G. Zhang, M. Yang, Q. Chen, F. Liu, J. Mac-
G. P. López, Adv. Funct. Mater. 2015, 25, 3122. romol. Sci., Part A 2010, 47, 335.
[68] Y.-G. Jia, X. X. Zhu, Chem. Mater. 2015, 27, 387. [103] D. C. Tuncaboylu, A. Argun, M. Sahin, M. Sari, O. Okay, Polymer
[69] L. Cai, R. E. Dewi, S. C. Heilshorn, Adv. Funct. Mater. 2015, 1344. 2012, 53, 5513.
[70] D. C. Tuncaboylu, M. Sahin, A. Argun, W. Oppermann, O. Okay, [104] G. Akay, A. Hassan-Raeisi, D. C. Tuncaboylu, N. Orakdogen,
Macromolecules 2012, 45, 1991. S. Abdurrahmanoglu, W. Oppermann, O. Okay, Soft Matter 2013,
[71] H. Wang, S. C. Heilshorn, Adv. Mater. 2015, 27, 3717. 9, 2254.
[72] G. Deng, F. Li, H. Yu, F. Liu, C. Liu, W. Sun, H. Jiang, Y. Chen, ACS [105] U. Gulyuz, O. Okay, Eur. Polym. J. 2015, 72, 12.
Macro Lett. 2012, 1, 275. [106] R. S. Jacob, D. Ghosh, P. K. Singh, S. K. Basu, N. N. Jha, S. Das,
[73] G. A. Barcan, X. Zhang, R. M. Waymouth, J. Am. Chem. Soc. 2015, P. K. Sukul, S. Patil, S. Sathaye, A. Kumar, A. Chowdhury, S. Malik,
137, 5650. S. Sen, S. K. Maji, Biomaterials 2015, 54, 97.
[74] W. J. Yang, X. Tao, T. Zhao, L. Weng, E.-T. Kang, L. Wang, Polym. [107] D. Rus, M. T. Tolley, Nature 2015, 521, 467.
Chem. 2015, 6, 7027. [108] Q. Chen, H. Chen, L. Zhu, J. Zheng, J. Mater. Chem. B 2015, 3,
[75] Y. Zhang, L. Tao, S. Li, Y. Wei, Biomacromolecules 2011, 12, 2894. 3654.
[76] T.-C. Tseng, L. Tao, F.-Y. Hsieh, Y. Wei, I.-M. Chiu, S. Hsu, Adv. [109] J. R. McKee, E. A. Appel, J. Seitsonen, E. Kontturi, O. A. Scherman,
Mater. 2015, 27, 3518. O. Ikkala, Adv. Funct. Mater. 2014, 24, 2706.
[77] B. Yang, Y. Zhang, X. Zhang, L. Tao, S. Li, Y. Wei, Polym. Chem. [110] S. Spoljaric, A. Salminen, N. D. Luong, J. Seppälä, Eur. Polym. J.
2012, 3, 3235. 2014, 56, 105.
[78] F. Ding, S. Wu, S. Wang, Y. Xiong, Y. Li, B. Li, H. Deng, Y. Du, [111] E. A. Appel, M. W. Tibbitt, J. M. Greer, O. S. Fenton, K. Kreuels,
L. Xiao, X. Shi, Soft Matter 2015, 11, 3971. D. G. Anderson, R. Langer, ACS Macro Lett. 2015, 4, 848.
[79] S. Lü, C. Gao, X. Xu, X. Bai, H. Duan, N. Gao, C. Feng, Y. Xiong, [112] J. Duan, J. Jiang, J. Li, L. Liu, Y. Li, C. Guan, J. Nanomater. 2015,
M. Liu, ACS Appl. Mater. Interfaces 2015, 7, 13029. 2015, 963436, DOI: 10.1155/2015/963436.
[80] S. Mukherjee, M. R. Hill, B. S. Sumerlin, Soft Matter 2015, 11, [113] W. Cui, J. Ji, Y.-F. Cai, H. Li, R. Ran, J. Mater. Chem. A 2015, 3,
6152. 17445.
[81] M. M. C. Bastings, S. Koudstaal, R. E. Kieltyka, Y. Nakano, [114] J. Liu, G. Song, C. He, H. Wang, Macromol. Rapid Commun. 2013,
A. C. H. Pape, D. A. M. Feyen, F. J. van Slochteren, 34, 1002.
www.advmat.de
REVIEW
[115] M. Zhong, Y.-T. Liu, X.-M. Xie, J. Mater. Chem. B 2015, 3, 4001. [130] J.-Y. Sun, X. Zhao, W. R. K. Illeperuma, O. Chaudhuri, K. H. Oh,
[116] K. Haraguchi, K. Uyama, H. Tanimoto, Macromol. Rapid Commun. D. J. Mooney, J. J. Vlassak, Z. Suo, Nature 2012, 489, 133.
2011, 32, 1253. [131] Y. Lin, G. Li, J. Mater. Chem. B 2014, 2, 6878.
[117] G. Gao, G. Du, Y. Sun, J. Fu, ACS Appl. Mater. Interfaces 2015, 7, [132] D. Ding, P. A. Guerette, J. Fu, L. Zhang, S. A. Irvine, A. Miserez,
5029. Adv. Mater. 2015, 27, 3953.
[118] X. Qi, Y. Guan, G. Chen, B. Zhang, J. Ren, F. Peng, R. Sun, RSC [133] J. Duan, J. Polym. 2015, 2015, 719529; DOI: 10.1155/2015/719529.
Adv. 2015, 5, 41006. [134] M. A. Khalily, M. Goktas, M. O. Guler, Org. Biomol. Chem. 2015,
[119] S. Huang, L. Yang, M. Liu, S. L. Phua, W. A. Yee, W. Liu, R. Zhou, 13, 1983.
X. Lu, Langmuir 2013, 29, 1238. [135] Q. Chen, L. Zhu, H. Chen, H. Yan, L. Huang, J. Yang, J. Zheng,
[120] Q. Wang, J. L. Mynar, M. Yoshida, E. Lee, M. Lee, K. Okuro, Adv. Funct. Mater. 2015, 25, 1598.
K. Kinbara, T. Aida, Nature 2010, 463, 339. [136] G. Li, H. Zhang, D. Fortin, H. Xia, Y. Zhao, Langmuir 2015, 31,
[121] J. E. Martin, A. J. Patil, M. F. Butler, S. Mann, Adv. Funct. Mater. 11709.
2011, 21, 674. [137] H. Yuk, T. Zhang, S. Lin, G. A. Parada, X. Zhao, Nat. Mater. 2016,
[122] M. Zhong, X.-Y. Liu, F.-K. Shi, L.-Q. Zhang, X.-P. Wang, 15, 190.
A. G. Cheetham, H. Cui, X.-M. Xie, Soft Matter 2015, 11, 4235. [138] C. Hui, R. Long, Soft Matter 2012, 8, 8209.
[123] M. Gerth, M. Bohdan, R. Fokkink, I. Voets, J. van der Gucht, [139] R. Long, K. Mayumi, C. Creton, T. Narita, C. Hui, Macromolecules
J. Sprakel, Macromol. Rapid Commun. 2014, 35, 2065. 2014, 47, 7243.
[124] L. Zhang, J. Qian, Y. Fan, W. Feng, Z. Tao, H. Yang, RSC Adv. 2015, [140] E. B. Stukalin, L.-H. Cai, N. Arun Kumar, L. Leibler, M. Rubinstein,
5, 62229. Macromolecules 2013, 46, 7525.
[125] U. Gulyuz, O. Okay, Macromolecules 2014, 47, 6889. [141] M. Guvendiren, H. D. Lu, J. A. Burdick, Soft Matter 2012, 8, 260.
[126] U. Gulyuz, O. Okay, Soft Matter 2013, 9, 10287. [142] S. E. Bakarich, R. Gorkin, M. in het Panhuis, G. M. Spinks, Mac-
[127] F. Yu, X. Cao, J. Du, G. Wang, X. Chen, ACS Appl. Mater. Interfaces romol. Rapid Commun. 2015, 36, 1211.
2015, 7, 24023. [143] S. Lin, H. Yuk, T. Zhang, G. A. Parada, H. Koo, Adv. Mater. 2015,
[128] D. C. Tuncaboylu, A. Argun, M. P. Algi, O. Okay, Polymer 2013, 54, 28, 4497.
6381. [144] R. P. Wool, Nature 2001, 409, 773.
[129] H. Zhou, G. Xu, J. Li, S. Zeng, X. Zhang, Z. Zheng, X. Ding, [145] S. Kim, C. Laschi, B. Trimmer, Trends Biotechnol. 2013, 31, 287.
W. Chen, Q. Wang, W. Zhang, Macromol. Res. 2015, 23, 1098. [146] R. Brazil, Chem. World 2016, 13, 54.

Advanced Materials - 2016 - Taylor - Self Healing Hydrogels

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Advanced Materials - 2016 - Taylor - Self Healing Hydrogels

Uploaded by

Copyright:

Available Formats

15214095, 2016, 41, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/adma.201601613 by Universidad del Bio Bio, Wiley Online Library on [15/01/2023].

structure after rheological deforma-

ferrocene) exhibited 100% self-recovery of the

and subsequent β-sheet structure formation of the peptide

and rapid. 100% mechanical characteristics were recovered in

natural system.[24] In the previous example,

hard and soft structures were formed simul-

You might also like