nature reviews materials https://doi.org/10.

1038/s41578-024-00672-3

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Design principles for strong

and tough hydrogels
Xueyu Li 1
& Jian Ping Gong 1,2

Abstract Sections

Hydrogels are crosslinked polymer networks swollen with water. Introduction

Owing to their soft and water-containing nature, hydrogels are Model of basic hydrogel
promising materials for applications in many fields, such as biomedical mechanics

engineering, soft robotics and environmental studies. One of the Design strategies
main obstacles to the practical application of hydrogels is their Conclusions and outlook
low mechanical strength and toughness. Since the 2000s, many
breakthroughs in the development of mechanically strong and tough
hydrogels have led to enormous advances in the study of soft materials
and our understanding of their failure mechanisms. Research has also
been conducted on long-term mechanical stability — that is, the cyclic
fatigue resistance and self-strengthening properties of hydrogels — to
enable their application as load-bearing materials. This Review provides
a comprehensive overview of the design principles for tough hydrogels.
Strategies to obtain self-growing and reinforced hydrogels that can
adapt to their surrounding mechanical environment are also presented.

Laboratory of Soft and Wet Matter, Faculty of Advanced Life Science, Hokkaido University, Sapporo, Japan.
1

Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, Sapporo, Japan.
2

e-mail: lixueyu@sci.hokudai.ac.jp; gong@sci.hokudai.ac.jp

Nature Reviews Materials

Review article
Introduction
As a combination of crosslinked solid and liquid components, hydro-
gels are similar to soft tissues in the human body and are promising
materials for uses such as scaffolds in tissue engineering1, medical
implants2 or wound dressings3. Many applications require hydrogels to
bear mechanical loads and to resist failure under static or cyclic load-
ing conditions. The macroscopic failure of materials originates from
the growth of small defects. The ability to resist defect growth — the
toughness — is correlated to the fracture energy Γ of materials, which
is the energy required for crack growth per unit area4. Typically, load-
bearing biological tissues have a high toughness. For instance, typical
fracture energies are ~2.5 kJ m−2 for skeletal muscle, ~1 kJ m−2 for carti-
lage and 20–30 kJ m−2 for tendons5. However, conventional synthetic
hydrogels, which are composed of a single non-uniform network of
hydrophilic polymers, are in general very weak, with low fracture energy
(<10 J m−2)6–8. This poor mechanical performance greatly limits the
application of such hydrogels. In addition to the toughness, elastic
modulus E (stiffness), fracture strength σf (strength), fracture stretch
ratio λf (deformability) and fatigue threshold Γ0 are important mechani-
cal parameters for applications. For a simple polymer network material,
these mechanical properties are correlated and conflicting. Increases
in elastic modulus and strength result in decreases in deformability,
fracture energy and fatigue threshold. Moreover, as hydrogels are
polymer networks swollen in water (solvent), these mechanical param-
eters are strongly related to the swelling ratio λs of the hydrogels. At the
equilibrium swelling, the swelling ratio is determined by the balance
of osmotic pressure and network elasticity9,10. Therefore, designing
and developing hydrogels with high toughness without sacrificing the
modulus and strength is a challenge.
The poor mechanical performance of conventional hydrogels is
attributed to several intrinsic features. One is the network inhomo-
geneity in polymer density distribution and polymer strand length
between the crosslinking points. Thus, hydrogels are susceptible
to stress concentration at loading, initiating cracks. Another is the
rubber-like elasticity caused by a lack of energy dissipation mecha-
nisms, resulting in low resistance against crack propagation. In addi-
tion, conventional hydrogels usually contain abundant water. The
low amount of load-bearing solid phase further results in weak and
fragile mechanical properties. Since the 2000s, the development of
mechanically strong and tough hydrogels11–18 has led to important
advances in the study of soft materials and our understanding of their
failure mechanisms. The main strategies to improve the mechanical
properties of hydrogels through their structural components can
be classified into three categories: the design of topological struc-
tures, such as slide-ring gels14,15,19–21, homogeneous four-arm gels22–25
and highly entangled gels26–28, to distribute stress in single-network
systems; the introduction of energy dissipation mechanisms by sac-
rificial bonds, such as in double-network (DN) hydrogels11,29–33 and
dual-crosslinked hydrogels13,34–39; and the introduction of high-order
structures, such as microphase separations16,40–43, microcrystals, and
fibrils or fabrics15,44–48. From the perspective of mechanical dynamics,
they can be classified into elastic and viscoelastic hydrogels that are
strain-rate independent and dependent, respectively, in the common
observation window.
Fatigue resistance — that is, long-term stability under cyclic loads —
is vital for some applications such as artificial cartilage. Since the ini-
tial work in 2017 (ref. 6), the study of fatigue-resistant mechanisms
and the development of fatigue-resistant hydrogels have attracted
considerable interest. Numerous antifatigue design strategies have
Nature Reviews Materials
been proposed. For elastic gels, these strategies involve modulations
at the molecular level, such as lengthening the polymer chain 49,50,
increasing entanglement26,27,51,52, and unfolding or degrading the
crosslinker53–57. For viscoelastic gels, mesoscale modifications have
been proposed, such as microphase separation42,58–60, microcrystalliza-
tion and fibrils18,47,61–65, and nanocomposites66–68. The fatigue threshold
is greatly enhanced for gels with hierarchical structures69, resolving the
conflict between the modulus and the fatigue threshold.
After about two decades of effort, nowadays the fracture energy
and fatigue threshold of hydrogels can reach ~200 kJ m−2 (refs. 16,44) and
~10 kJ m−2 (ref. 18), respectively. Elastic modulus from submegapascal
to hundreds of megapascals, strength from submegapascal to tens of
megapascals, and stretching ratio from several to hundreds70,71 can be
achieved. Moreover, taking inspiration from biological systems, efforts
have been made to develop self-healing hydrogels and anisotropic hydro-
gels. Unlike other solid materials, hydrogels are permeable to small
molecules. Thus, hydrogels could be used as an open system to develop
mechanically triggered new network growth. Self-growing and strength-
ening hydrogels based on mechanochemistry mechanisms have also
attracted attention for the purpose of developing materials that adapt
to their surrounding environment, resembling biological systems72,73.
The advancements in hydrogel design strategies, focusing on
achieving comprehensive mechanical performance, have been summa-
rized in several outstanding review papers, particularly those empha-
sizing the structure of polymer networks5,74 and the nonlinear elastic
fracture mechanics75. Given the importance of swelling and deswelling
characteristics in hydrogels, and the practical need for hydrogels to
be in an equilibrium state of swelling in a liquid medium, this Review
explores design strategies to attain high mechanical performance with
a focus on the perspective of swelling and deswelling. We initially use a
basic hydrogel model to clarify the influences of the molecular structure
and swelling or deswelling on the mechanical properties, encompass-
ing the elastic modulus, extensibility, strength, toughness and fatigue
resistance. We then discuss the main design strategies to obtain tough
hydrogels, followed by advances in developing fatigue-resistant hydro-
gels and in understanding their underlying mechanisms. We highlight
recently developed strategies for developing self-reinforcement hydro-
gels with tissue-like self-growing properties. To close, we emphasize
challenges and trends in developing inelastic fracture mechanics theory
to capture the large deformation behaviour and the next generation of
tough hydrogels for practical biological applications.
Model of basic hydrogel mechanics
Various theoretical models, including the classic Flory–Rehner statis-
tical model9, Arruda–Boyce eight-chain constitutive model76 and Gent
continuum mechanics model77, along with their combinations10,78, have
been explored to explain the swelling and large deformation of polymer
networks. These models are discussed in reviews elsewhere79–82. Here,
we analyse a simple affine network to represent the structure of a hydro-
gel, and we discuss its rubber elasticity and fracture at different swell-
ing states. The hydrogel features a uniform polymer network
comprising strands characterized by the number of Kuhn monomers
in each strand (Nx) and the length of each monomer (b) (Fig. 1a). In the
reference state, the end-to-end distance of each strand (R0) follows an
ideal Gaussian chain, approximately given by R0 ≃ bNx 1/2, and the net-
work has a strand density denoted as νx,0 (refs. 76,83). On contact with
water, the hydrogel undergoes a size change by a factor of λs in length
(λ s > 1 indicates swelling, and λ s < 1 indicates deswelling). Operating as
an affine network, where the deformations of the bulk hydrogel and
Review article
individual network strands are identical83,84, the end-to-end distance
of a strand becomes R = λ sR0. Consequently, the strand density trans-
−3
forms to νx,0λ s (Fig. 1a). Subsequently, we investigate the influence
of λs on the elastic modulus, stretchability and fracture characteristics of
the hydrogel in the absence of viscoelastic effect, unless specified.
Elastic modulus
The Young’s modulus (E) of a hydrogel is determined by the product
of the elasticity (k) or stiffness per strand and the density of strands
−3 −3
(νx,0λ s ), expressed as E = kνx,0λ s . As the elasticity of a strand increases
with swelling (λs > 1) and strand number per volume decreases with
swelling, E exhibits a non-monotonic dependence on λs. In this context,
we use the freely jointed chain model to represent the elastic energy of
a strand, considering the finite extensibility effect (see Supplementary
Information)85,86. By taking the second derivative of the elastic energy
of a strand with respect to the stretching ratio, we derive the elasticity of
the strand, expressed as:
2 3 + α4
k = kBTλ s (1)
(1 − α 2) 2
where α = R
λ R
s 0 λ
≃ 1/2
s
. Consequently, the Young’s modulus of the hydrogel
max Nx
is given by:
ve,0kBT 3 + α 4
E= (2)
λ s (1 − α 2) 2
λ sR 0 R
In Fig. 1a, we depict E/E0 as a function of α = R max for Rmax ≃ Nx 1/2 =
0
20 as a representative example. Here E0 = 3ve,0kBT is the Young’s modu-
lus of the hydrogel at the reference state (λ s = 1, α ≃ 0). The curve in
Fig. 1a illustrates the non-monotonic evolution of the elastic modulus
with swelling ratio. For small or modest λ s, where λ s R0 is much smaller
than the contour length of the strand Rmax = bNx, polymer strands can
be approximated as Gaussian chains, and the elasticity is proportional
2
to λ s . Therefore, E decreases as λ s increases because the strand density
−3
is proportional to λ s . For large λ s where λ s R0 approaches Rmax, the
stiffness of strands increases rapidly owing to the limited extensibility
of the strand85. The increase of strand stiffness with λ s is much stronger
2
than λ s , surpassing the effect from the decrease of strand density and
resulting in an increase of E with λ s.
For a deswelling hydrogel (λ s < 1), when there are physical interac-
tions between polymer strands, the elastic modulus comprises two
̇ where Epr is from the primary network and increases
terms, E = Epr + E(ε),
with deswelling (Fig. 1a, regime C), and E(ε)̇ is from dynamic crosslink-
ing of interstrand physical bonds and changes with the observation
time (or strain rate ε)̇ relative to the characteristic relaxation time (τ)
of the viscoelastic hydrogel. At low strain rate (ετ̇ ≪ 1), the dynamic
bonds have little contribution (E(ε)̇ ≃ 0) to the modulus, and the hydro-
gel behaves as a soft solid with elastic modulus Epr, like the elastic
hydrogel. At high strain rate (ετ̇ ≫ 1), the dynamic bonds play a similar
role to the permanent crosslinking, and the hydrogel behaves as a hard
̇ In the intermediate strain rate, the modu-
elastic solid with a large E(ε).
lus increases as the strain rate increases (viscoelastic regime). The mod-
ulus of viscoelastic hydrogels typically follows the time–temperature
superposition principle, as the bond association time is strongly
temperature dependent and influences τ (refs. 83,87,88).
Maximum stress and stretch ratio
The theoretical maximum stretching ratio ( λ max) and engineering stress
(σmax) strongly depend on the swelling behaviour. Here we use a simple
1D model to see the effect of λ s on λ max and σmax. Under deformation,
Nature Reviews Materials
the maximum stretch ratio of a single strand, which goes from λ sR0 to
its physical limit or contour length (Rmax = bNx), is
Rmax Nx 1/2
λ max = ≃ (3)
λ s R0 λs
The maximum engineering stress, which is the product of a single
strand’s rupture force ( fb) and the areal density of strands crossing the
plane perpendicular to the loading direction in the undeformed state
3
(Σ ≃ λ sR0νx ,0 / λ s ), is given by
fb bC0
σmax ≃ 1/2 (4)
2
λ s Nx
Here, the monomer concentration in the as-synthesized state is
C0 = νx ,0Nx . From equations (3) and (4), the true maximum stress
(σmax T = σmaxλ max ) of the simple hydrogel is proportional to the bond
3
rupture force and bond density of the network (C0 /λ s ), independent
of Nx.
f bC0
σmax T ≃ b 3 (5)
λs
Thus, the stretchability and strength of a hydrogel decrease by
swelling.
Stress concentration effect
For real hydrogels, as for other brittle materials, the theoretical σmax T
has never been observed macroscopically because of stress concentra-
tion at defects or crack tips. For hydrogels for which nonlinear elastic
fracture mechanics apply, two characteristic lengths, the nonlinear
elastic length (ℓ, denoted as the distance from the crack tip below which
the deformation is dominated by elastic nonlinearity at the onset of
crack initiation)75 and defect-insensitive length (ξ, denoted as the
critical crack length for the transition from defect-insensitive to defect-
sensitive rupture)89 or dissipative length, are important75. The true
tensile stress σ T around the crack tip inversely scales with the distance
from the crack tip (r), provided that the length of a defect or crack (c)
exceeds a certain nonlinear elastic length ℓ , and r is in the range of
ξ < r < ℓ < c (refs. 75,84) (Fig. 1b).
Γ
σ T (r ) ≃ (when ξ < r < ℓ < c) (6)
r
Here, the fracture energy Γ represents the energy required to cre-
ate a unit surface by propagating a pre-existing crack. The true stress
converges to the external stress applied to the material when the dis-
tance from the crack is much larger than the crack size (r ≫ c). There-
fore, even if the applied stress is still far below the theoretical maximum
stress σmax T, the σ T(r ) near a defect could already reach σmax T, resulting
in material failure. Owing to this stress concentration effect at the crack
tip, the elastic energy per unit volume that a soft material can store
before undergoing rupture (Wb) decreases inversely proportional to c,
provided that c exceeds ξ (ref. 75) (Fig. 1c).
Γ
Wb ≃ (when c > ξ ) (7)
c
For an elastic hydrogel, Wb corresponds to the area under the
stress–strain curve of the material. Thus, Wb is not an intrinsic material
parameter and depends on the pre-existing crack length c. Equation (7)
explains why in real hydrogels, in which defects inevitably exist, the
Review article

a Hydrogel swelling behaviour and its effect on elastic modulus b True stress as a function of distance r to the crack tip
Г
~
r Crack
Crosslink σT

1
ln(σT)

R0
Swell (λs > 1) Deswell (λs < 1) Applied σT

Elastic Viscoelastic

ln(ξ) ln(l) ln(c)

ln(r)
Dynamic
bonds
c Critical strain-energy density at crack initiation as a function
of crack length c
b
λsR0 Г/c
σ
Nx monomers W*
λsR0
c
λs < 1 λs > 1
3 Wb
C
B

1
E/E0

A Flaw Flaw
insensitive sensitive
0.3 ξ

Crack length c
Nx = 400
0.1
0.03 0.1 0.3 1
λs/Nx½

d Fracture energy of hydrogels Polymer chain lying across the crack propagation plane
Г0: Lake–Thomas model Nx monomer units Crack
σ

λcH0 ГD Crack growth λsR0

Plane of crack
propagation

Crosslink
Г = Г0 + ГD

λ
~10 nm ~0.1–1 mm ~1–10 mm ~1 mm ~10 mm
ГD ∝ dissipation lengths Simple network Double network Dual-crosslinked Strain-induced Fibre reinforcement
viscoelastic network crystallization

Nature Reviews Materials

Review article
Fig. 1 | Hydrogel swelling, deswelling and fracture behaviours. a, Schematic
depiction of hydrogel swelling behaviour and its influence on the elastic
modulus. The top panel shows an affine network hydrogel in its reference state.
In the middle panels, the hydrogel undergoes swelling or deswelling by a length
factor of λs. The bottom panel shows the elastic modulus (E) of the hydrogel as a
function of λs, where E is normalized by its value at the reference state (E0), and λs
is normalized by the maximum allowable value ( Nx1/2). In practice, hydrogels
exhibit distinct behaviours: typically, a neutral hydrogel swells modestly, and λs is
in the regime where E/E0 decreases (regime A); a strong polyelectrolyte hydrogel
swells substantially, and λs can access the regime where E/E0 increases (regime B);
and a hydrogel containing dynamic bonds deswells in water, and E/E0 is greater
than 1 (regime C). b, True stress distribution along the principal axis as a function
of distance r to the crack tip for soft materials, based on nonlinear elastic fracture
mechanics theory. ξ and l are the dissipative length and nonlinear elastic length,
respectively. c, Critical strain-energy density Wb at crack initiation as a function
fracture stretch ratio ( λ f ) and engineering stress σf vary from sample
to sample and are much smaller than λ max and σmax predicted from their
average structure.
Fracture energy
The fracture energy Γ is an intrinsic material parameter for charac-
terizing a material’s toughness. For the swelling elastic hydrogel, the
Lake–Thomas model90 provides a description for Γ as the energy needed
to break a single layer of strands intersecting the crack plane:
2
Γ ≃ NxUbΣ ≃ bUbC0Nx 1/2/λ s (8)
Here, Ub represents the activation energy required to break a
chemical bond in the backbone of strands. The Lake–Thomas model
postulates that the energy needed to break an individual strand is dir­
ectly proportional to the monomer number of that particular strand
(Nx). This proportionality arises because all the bonds in the strand back-
bone are arranged in series, necessitating the stretching of each bond
to the same energy state (Ub) to induce bond rupture (Fig. 1d). By insert-
ing equations (5) and (8) into equation (6), the defect-insensitivity
length or energy dissipative length ξ for the model elastic hydrogel is
found to be of the order of the end-to-end distance of the polymer
U
strands (the network mesh size), ξ ≃ bfb λ sR0 ≃ R.
b
To bolster a material’s strength, reducing the stress concentration
is crucial, as underscored by equations (6) and (7). Increasing ξ, reduc-
ing the size of defects or cracks (c), and increasing the energy required
for crack propagation (Γ) are potential strategies. For improving Г, the
central idea is to incorporate additional energy-dissipating mecha-
nism from a processing zone at the crack tip that extends beyond
the network mesh size. The total fracture energy can be expressed
as the sum of two components: Г = Г0 + ГD, where Γ0 represents the
dissipation directly related to breaking the polymer strands bridging
the crack (the intrinsic fracture energy) and can be described by the
Lake–Thomas model (Fig. 1d), and ΓD accounts for the contribution
of mechanical energy dissipation from the process zone. The process
zone also increases the defect-insensitivity length ξ. Different molecu-
lar designs can substantially increase the crack-tip processing zone
(Fig. 1d). For a deswelling hydrogel that is dual crosslinked, the vis-
coelasticity resulting from the dynamic bonds brings intrinsic energy
dissipation mechanisms.
The Γ of elastic gels can be experimentally measured based on
Griffith’s theory for a brittle fracture91. The theory postulates that a
Nature Reviews Materials
of crack (defect) length c. W* is the critical strain-energy density for rupturing a
material in the absence of large cracks of c > ξ. d, Fracture energy Γ of hydrogels.
H0 is the initial height. λc is the critical stretch ratio where the pre-existing crack
starts propagation. In general, Γ = ΓD + Γ0, where ΓD is correlated to the energy
dissipation in the processing zone and increases with dissipation length ξ, and Γ0
is intrinsic fracture energy, correlated to the energy required to break polymer
chains lying across the crack plane by a unit area. For a simple network, Γ = Γ0 and
Γ0 can be described by the Lake–Thomas model. The typical processing zone sizes
(or dissipation length) are ~10 nm, ~0.1–1 mm, ~1–10 mm, ~1 mm and ~10 mm for
simple network hydrogels, double-network hydrogels, dual-crosslinked
viscoelastic hydrogels, strain-induced crystallization hydrogels and fibre-
reinforced composites, respectively75. Panels b,c and d adapted with permission
from ref. 75, Annual Reviews. Panel d adapted with permission from ref. 69, Royal
Society of London.
pre-existing crack will extend when the rate of strain-energy release
from the stress field around the crack is at least equal to the rate at
which it is absorbed by crack extension. Commonly used experimental
setups for measuring the fracture energy for the crack initiation (the
onset of crack propagation) can be found in the literature4,12,92,93.
Design strategies
In practice, hydrogels typically undergo swelling when immersed in
water after synthesis. The reference state of the model hydrogel
described in the theoretical section may correspond to the as-synthe-
sized hydrogel. The swelling ratio λ s of a hydrogel in the equilibrium
state is governed by the equilibrium between the osmotic pressure
arising from the polymer–solvent (water) mixing free energy and the
network elasticity of the hydrogels, which can be described by
the Flory−Rehner theory9.
Generally, hydrogels made from neutral polymers display mod-
est swelling, leading to a decrease in the elastic modulus on swelling
(Fig. 1a, regime A). By contrast, polyelectrolyte hydrogels, where ionic
osmotic pressure from Donnan equilibrium contributes to excessive
swelling in pure water, result in an increase in E with swelling94,95 (Fig. 1a,
regime B). When physical bonds can be formed between polymer
strands, hydrogels undergo deswelling after synthesis39,96,97.
For a swelling gel (λ s > 1 ), the equilibrium λ s increases as Nx
increases83,94,98, whereas for a deswelling gel (λ s < 1), the equilibrium λ s
is barely dependent on Nx (refs. 41,42). Nx decreases as chemical
crosslinker density increases. Swelling hydrogels typically exhibit
elastic behaviour with negligible interstrand interaction. On the other
hand, deswelling hydrogels usually exhibit viscoelastic behaviour due
to physical bonds among polymer strands (Fig. 1a). It is important to
note that there are exceptions to these patterns99,100. This Review
focuses on discussing these two typical patterns.
Elastic hydrogels (typically λs > 1)
In real hydrogels, there are inherent variations in both the distribution
of polymer density and the length of a polymer strand (Fig. 2a). There-
fore, hydrogels naturally contain numerous defects. A single, relatively
large defect produces remarkable stress concentration and triggers
crack propagation, resulting in the failure of hydrogels at macroscopic
stress levels that are much lower than theoretical averages would sug-
gest (equations (6) and (7)). Because elastic hydrogels have no energy
dissipation mechanism during deformation, real swelling hydrogels are
typically very weak, and the failure behaviour is hard to predict, owing
Review article
a Conventional hydrogel b Topological design for tough hydrogel
Ideal network
c Double-network hydrogel
First network: rigid and brittle
No interaction between first network and second network
Chemical crosslinking: swollen (elastic)
Load
Unload
First network
Reversible crosslinking: usually used
at as-prepared state (viscoelastic)
Load
Unload
Fig. 2 | Swelling (elastic) hydrogels. a, Structure of conventional hydrogel. b, Topological structure hydrogels. c, Double-network hydrogels. Panel b adapted with
permission from ref. 26, AAAS, and with permission from ref. 108, AAAS. Panel c adapted from ref. 200, Springer Nature Limited.
to their heightened vulnerability to defects. Enhancing the toughness
of elastic hydrogels is a definite challenge.
Topological structure. Reducing spatial heterogeneities through the
realization of an ideally homogeneous network, movable crosslinkers
or scission mechanisms can improve stress homogenization (Fig. 2b).
Hydrogels made from well-defined symmetrical tetrahedron-like poly-
ethylene glycol (PEG) macromonomers22–25 have fewer spatial heteroge-
neities101–103 than hydrogels obtained from free radical polymerization
and thus show improved failure strength and extensibility due to a
lower amount of defects22,104. However, the fracture energy of such gels
lies in the range estimated from the Lake–Thomas model (<100 J m−2)105,
because the network homogeneity improves the strength but not
the fracture energy, consistent with the theorem for simple elastic
network fracture.
For a purely elastic hydrogel, a large Nx (which can be achieved
by reducing the chemical crosslinking density) results in increases
in stretchability λmax and fracture energy Γ, but decreases in elas-
tic modulus E and strength σmax. Therefore, there exists a tradeoff
Nature Reviews Materials
Force-triggered
Slide-ring Dense entanglement cycloreversion
Second network: flexible Double network: tough and robust
and stretchable
Interaction between first network and second network
Deswelling in water (viscoelastic)
First network Second network
Load
Unload
Dynamic bonds
between these quantities. Hydrogel swelling (λs) reduces Γ, σmax and
λmax. Hence, simultaneously optimizing these properties in purely
elastic hydrogels necessitates molecular designs that go beyond the
constraints of a basic elastic network. For example, slide-ring hydro-
gels14 can equalize the tension of polymer chains. In these hydrogels,
the polymer chains are topologically interlocked by figure-of-eight
polyrotaxane crosslinks, which can pass along the polymer chains
freely in a manner similar to pulleys. As a result, the strand length
between two crosslinked junctions (Nx) increases as the figure-of-
eight crosslinks slide away from each other and redistribute loads19,90,
resulting in a higher extensibility and stronger crack growth resistance
compared with fixed crosslink gels106. Another strategy to transmit
tension around the notch consists in applying dense entanglements
as slip links to fabricate single-network polyacrylamide (PAAm)
hydrogels — with polymer volume fraction around 10 vol% — that are
stiff (E = 0.1 MPa) and stretchable (fracture stretch ratio λf = 4.5) and
have superior fracture energy compared with conventional PAAm
hydrogels of similar modulus (Г up to 2 kJ m−2 compared with 10−2
to 10−1 kJ m−2)8,26,107. The large number of trapped entanglements
Review article
contribute to the modulus and strength, whereas the slip of entan-
glements at the crack tip lengthens the strands, resulting in large
fracture energy simultaneously. Weak side-crosslinker scission is
another strategy, in which the side crosslinkers are preferentially
cleaved under force, resulting in lengthening of the strands. This
strategy can enhance the fracture energy ninefold without sacrificing
the modulus108. To demonstrate the toughening effect of hydrogels
fabricated through different strategies, we summarize the mechani-
cal performances and corresponding water content of various types
of hydrogels (Table 1). We can see that the tradeoff between modulus
and fracture energy can be resolved by movable or weak crosslinker
mechanisms (Table 1). Hydrogels with topological designs have the
advantage of negligible hysteresis, which can avoid stress soften-
ing and relaxation during practical applications. Because they have
no built-in energy dissipation mechanisms, the fracture energy of
such systems, in principle, can be described by a modified Lake–
Thomas model in which multiple network layers near the crack plane
participate in dissipating energy109,110.
Double-network structure. Swelling hydrogels are elastic and
thus do not dissipate energy during deformation. The invention of
the DN structure with built-in sacrificial bonds and energy dissipa-
tion mechanisms was a breakthrough for that class of hydrogels11.
DN hydrogels consist of two interpenetrating elastic networks with
contrasting properties (Fig. 2c) obtained by a two-step sequential
polymerization process. The first network, which is rigid and brit-
tle, acts as a sacrificial bond network that effectively dissipates
energy. Meanwhile, the second network is soft and ductile, ensur-
ing the hydrogel’s integrity during deformation11,32. Despite having
a high water content (~90 wt%), DN hydrogels are stiff, strong and
tough; the fracture energy is even comparable to industrial rub-
bers and natural cartilage30. Achieving exceptionally high elastic
modulus, strength and fracture energy in DN hydrogels revolves
around two key aspects. The first network should be more brittle
and weaker than the second network, that is, it should have a smaller
fracture stretch ratio (λf ) and fracture stress (σf ). Conventional DN
gels usually use highly crosslinked polyelectrolyte networks (such
as PAMPS (poly(2-acylamido-2-methylpropanesulfonic acid)) and
PAAc (poly(acrylic acid))) as the first network, and slightly crosslinked
neutral polymers (such as PAAm, PDMAAm (poly(N,N-dimethylacryla-
mide)) and PHEMA (poly(2-hydroxyethyle methacrylate))) as the sec-
ond network. The highly crosslinked polyelectrolyte network, which
over-swells in water owing to high osmotic pressure from counterions
(Fig. 1a, regime B), is both brittle (small λf ) and weak (small σf ) while
exhibiting a high Young’s modulus29. In addition, the monomeric molar
ratio between the sparsely crosslinked second neutral network and
the first network should range from several to a few tens, resulting
in larger λf and σf. The mechanical contrast between the two elastic
networks results in inelastic behaviour, the DN hydrogel exhibiting
yielding and necking during tensile loading111 and substantial hyster-
esis during cyclic loading112. Because the second network suppresses
the stress concentration in the defects of the first network, the yield-
ing stress is much higher in comparison to the fracture stress of the
first network alone. Above the yielding point, the short-strand first
network is considered to rupture into fragments, dissipating energy,
whereas the stretchable second network maintains structural integrity
and sustains further elongation113,114. In fracture tests, covalent bond
rupture in the first network ahead of the propagating crack forms a
damage zone with a thickness of several hundred micrometres, and the
Nature Reviews Materials
ruptured first network causes large softening and stress–strain hys-
teresis, contributing to a substantial ГD (refs. 115–118) (Fig. 1d). This
internal fracture phenomenon has been confirmed by luminescent
probes31,119–122 and real-time birefringence123,124. Furthermore, the bro-
ken fragments of the first network could serve as sliding crosslinks
to further delocalize the stress concentration around the crack tip
and prevent chain scissions125. Therefore, the combination of the two
networks enhances resistance to crack propagation, resulting in high
fracture energy comparable to cartilage and tendon126,127.
Viscoelastic hydrogels (typically λs < 1)
Viscoelastic hydrogels have an intrinsic energy dissipation mecha-
nism, and they typically exhibit a large, self-recoverable mechanical
hysteresis because the physical bonds dynamically break and reform.
The mechanical properties strongly depend on the structure (dynamic
bond strength and density) and the observation condition (strain rate
and temperature). The fracture energy strongly depends on the crack
propagation velocity (vc) and temperature (T), and can be expressed as
Γ(vc,T) = Γ0(1 + f(vc,T)) (ref. 87). When vc approaches zero, the fracture
energy reduces to Γ0, which is determined by the primary network
structure (equation (8)).
Dual-crosslinked hydrogels. Because deswelling hydrogels typically
have two crosslinking mechanisms (covalent and non-covalent), they
are also known as dual-crosslinked hydrogels. The non-covalent bonds
can dissociate and reassociate dynamically, dissipating energy and pro-
tecting the primary network crosslinked by chemical bonds from stress
overshoot. Thus, the dynamic bonds function as reversible sacrificial
bonds to dissipate energy. Various kinds of non-covalent bonds, includ-
ing borate/di-diol complexation, electrostatic interaction, hydrogen
bonds, metal–ligand coordinate bonds, hydrophobic interaction, π–π
interaction, cation–π interaction and host–guest interaction, have
been used (Fig. 3a). Synthesis of this type of hydrogel is simple and
usually involves a one-step reaction to form the chemically crosslinked
primary network. Non-covalent interactions are induced by post-
treatments, such as dialysis to remove counterions for polyampholy-
tes, or immersion in a multivalent ion solution to form coordination
complexes. During post-treatment, intrachain and interchain dynamic
bonds are formed and reorganized to form aggregations, causing the
polymer strands to collapse into globule conformation, analogous to
the folded structure of proteins. Therefore, these hydrogels deswell in
water (λs < 1) after post-treatment, resulting in a high polymer volume
fraction (around 50 vol%).
Here we take the hydrogen bond as an example, but examples
of hydrogels containing other non-covalent bonds can be found in
comprehensive reviews5,128,129. Hydrogen bonds are ubiquitous in living
systems, contributing to the formation of secondary structures in pro-
teins. When designing tough hydrogels based on hydrogen bonds, the
presence of water molecules in hydrogels can disrupt the bonds, poten-
tially limiting the stability of dynamic bonds34. Therefore, to stabilize
the hydrogel, formation of multiple hydrogen bonds between mono-
mer pairs is required34,130, or the hydrogen bonds can be further stabi-
lized by hydrophobic interactions131,132. For instance, the chemically
crosslinked PAAm hydrogel exhibits swelling behaviour and no self-
healing property because its hydrogen bonding is attacked by water. By
contrast, after the PAAm hydrogel is synthesized in the presence of tan-
nic acid, which can form multiple hydrogen bonds between the PAAm
polymer and tannic acid, the gel deswells in water with self-healing
ability97. The deswelling behaviour of PAAm–tannic-acid hydrogel
Review article

Table 1 | Mechanical properties of representative swelling and deswelling hydrogels

Category Main Water Young’s Fracture Fracture Work of Fracture Fatigue threshold Comments Refs.
components content modulus stretch stress σf extension energy Γ
(wt%) (MPa) ratio λf (MPa) Wb (MJ m−3) (kJ m−2) Γ0 (J m )
−2
Observation
resolution

Elastic hydrogels
Homogeneous Tetra-PEG ~90 0.001–0.01 2–8 0.025–0.2 0.015–0.85 0.02–0.07a 12.2 ~20 nm per – 23,181,
network cycle 194
Slide-ring gel PEG with ~90 0.009–0.08 12–15 0.02–0.12 NR 0.002–0.25b NR NR Amorphous 14,106,
polyrotaxanes 195
Dense PAAm 70–99 ~0.1 Up to 5 0.39 NR 0.1–2b 200 ~1 nm per – 26
entanglement cycle
Polyprotein PAAm ~95 0.012 11 0.08 NR 0.9b 126 ~10 nm per – 53
crosslinkers crosslinked by cycle
polyprotein
crosslinkers
DN gels PAMPS–PAAm ~90 0.1–1.0 10–32 1–10 11 1–4.5a 41–400 ~1 nm per – 32,49,
cycle 50,127,
196
Viscoelastic hydrogels
DN gels with Ca2+-alginate– ~86 0.01–0.11 2–23 0.03–0.25 NR 0.025–9b 35–50 ~1 nm per Not water 12,133,
physical PAAm cycle equilibrium 197
interactions
Dual-crosslinked P(NaSS-co- ~50 0.08–0.4 5–33 0.19–0.55 0.93–2.8 1.5–4a,b 10–100 ~1 nm per Water 40,42,
(ionic bond) DMAEAQ) cycle equilibrium 58,140
Supra­molecular PNAGA 70–86 0.05–0.15 7–16 0.16–1.1 NR 0.2–1.2a NR NR No chemical 34
hydrogel crosslinker
(hydrogen bond)
Dual-crosslinked Zr4+-P(AAm-co- 33–74 0.4–28.5 3.2–13.5 2.1–11.6 NR 3.7–24.2a NR NR – 198
(coordination AMPS)
complex)
Dual-crosslinked PAAm–DVB 86 0.027–0.9 > 102 0.4–1.5 7.3–18.8 2.5–26b 2,500 ~1 μm per – 71
(hydrophobic cycle
interaction)
Hydrogels with high-order structure
Bilayer lamellar PDGI–PAAm 93–98 0.005–0.12 8–24 0.05–0.6 Up to 5 5b NR NR – 154–157
structure
Strain-induced Slide-ring PEG 60–80 ~0.2 13–15 1–5.5 6.6–22 2.9–3.6c NR NR – 15
crystallization
Phase separation PAAc–calcium 39–74 3.4–131 1.6–7 0.19–17.9 0.16–9.6 NR NR NR – 16
(ionic bonds) acetate
Microcrystal and PVA 58–90 0.03–10 Up to 30 0.3–23.5 Up to 210 0.1–170b,c 150– ~1 nm per – 5,18,64,
nanofibre 10,000 cycle 145,149,
150
Microfibre DCC-alginate ~60 59–342.4 1.35–3.7 19.8–81.5 7.04–38 NR NR NR – 48,199
and cellulose
Fibre-woven PA–GF 38 606 NR 380 N mm−1 d NR 100–250a NR NR – 44,179
fabrics
Composite 2D PVA–GO 80 10 3.3 8 Ca. 10 NR 1,500 ~1 nm per – 67
composite cycle
hydrogel
DCC, drying under confined conditions; DN, double network; DVB, divinylbenzene; GO, graphene oxide; NR, not reported; PAAc, poly(acrylic acid); PAAm, polyacrylamide; PA–GF, woven
glass fibre fabric–polyampholyte hydrogel composite; PAMPS, poly(2-acylamido-2-methylpropanesulfonic acid); PDGI, poly(dodecyl glyceryl itaconate); PEG, polyethylene glycol; PNAGA,
poly(N-acryloyl glycinamide); P(NaSS-co-DMAEAQ), sodium styrenesulfonate and acryloyloxethyltrimethylammonium chloride copolymer; PVA, polyvinyl alcohol. aFrom tearing test; bfrom
pure shear tests; cfrom simple extension; dtearing strength.

is conducive to high extensibility (λf up to 16) and tensile strength crack propagation, imparting a high fracture energy to the hydrogel
(σf up to 2.5 MPa). In addition, the multiple hydrogen bonds between (Г up to 3.1 kJ m−2), nearly 30 times higher than that of PAAm gels solely
the polymer and tannic acid effectively dissipate energy and suppress crosslinked through chemical crosslinking.

Nature Reviews Materials

Review article
Double-network gels with physical interactions. Traditional DN gels
are composed of two chemically crosslinked elastic networks, but DN
gels can also be formed by combining a physically crosslinked and a
chemically crosslinked network. For example, DN hydrogels from Ca2+
crosslinked alginate network and chemically crosslinked PAAm network
exhibit partial self-recovery and a high fracture energy of ~9 kJ m−2 in
the as-prepared state, highlighting the beneficial effect of the dynamic
bonds10. However, owing to osmotic pressure, this DN hydrogel swells in
water and becomes weaker than in its as-prepared state12,133,134. DN gels
containing no chemically crosslinked network have also been devel-
oped. For example, combining an amphiphilic triblock copolymer as
the first network and a linear PAAm as the second network, a deswollen
water-equilibrated block copolymer PAAm DN hydrogel was synthe-
sized (water content ~50 wt%)135,136. The amphiphilic triblock copolymer
PBMA-b-PMAA-b-PBMA (poly(butyl methacrylate)-b-poly(methacrylic
acid)-b-poly(butyl methacrylate)) forms a hyperconnective physical
network through strong hydrophobic associations of the end-block
PBMA135. Simultaneously, the midblock PMAA forms hydrogen bonds
with the linear PAAm chains to allow energy dissipation (Fig. 2c). The
hydrogels show abnormally large non-softening, and quasilinear but
inelastic deformation, and they have high elastic modulus (1.7 MPa),
fracture energy (Г ≈ 3 kJ m−2), strength (σf ≈ 10 MPa), extensibility (λf ≈ 7)
and quick self-recovery (85% recovery within 5 min).
Hydrogels with high-order structure
Introducing high-order structures, such as microphase separa-
tion structures, microcrystals and fibrils, fibre-woven fabrics and
a Dual-crosslinked hydrogel
Deswelling in water (viscoelastic)
Physical crosslinking/ Chemical crosslinking Dual crosslinked
supramolecular network Tough and self-healing
+
b Hydrogel containing load-bearing high-order structure
Deswelling in water (viscoelastic) Partly deswelling in water (viscoelastic)
Phase separation Fibre Crystal
Fig. 3 | Deswelling (viscoelastic) hydrogels and hydrogels with high-order
structure. a, Dual-crosslinked hydrogel composed of a primary network from
chemical crosslinking and/or trapped entanglement and dynamic networks
Nature Reviews Materials
nanocomposites, are effective approaches for toughening hydrogels
(Fig. 3b). Interplays between hierarchical structures from molecular
to mesoscopic scales endow strong crack resistance. Particularly, the
processing zone is enlarged because of the increase in the load-transfer
length by submicrometre-scale to centimetre-scale stiff constituents,
resulting in a large ГD. Meanwhile, the Г0 can be enhanced by two to
four orders of magnitude. Consequently, incorporating reinforcement
components is one of the most effective strategies to substantially
enhance both fracture energy and fatigue threshold simultaneously,
to a level even better than bio-tissues (Fig. 4).
Microphase separation. Deswelling hydrogels are prone to microphase
separations, forming polymer-dense phases and polymer-sparse phases
at scales much larger than the dual-crosslinked structure (Fig. 3b).
The size of the microphases is governed by the competition between
enthalpic gain of the physical interactions and entropic penalty of the
primary network. The interplay of the molecular and mesoscale hier-
archical structures dissipates a substantial amount of energy through
a large load-transfer length. For example, polyampholyte hydrogels
(PA gels)13,137 copolymerized from cationic and anionic monomers
at high monomer concentrations around the charge balance point
form a bicontinuous microphase separation, in which the hard micro-
phase network and soft microphase network are interpenetrated41,138.
The PA gels shrink to approximately 40% in volume when immersed
in water to dialyse counterions. During dialysis, the conformation of
the polyampholyte strands changes from coil to aggregated globule.
Water-equilibrated PA gels exhibit a polymer volume fraction ~50 vol%,
– +
PVA–borate ions Ionic bond
H O
N HO M
R
Physical crosslinking/ Hydrogen bond Coordination complex
supramolecular network
Hydrophobic interaction π–π interaction
Cation–π interaction Host–guest interaction
Usually used in the
as-prepared state
Bilayer lamellar structure Nanocomposite
d1
d2
d1 ≈ 4.7 nm
d2 ≈ hundreds nm
from physical crosslinking. b, Hydrogel containing high-order structure. PVA,
polyvinyl alcohol. Panel b adapted with permission from ref. 40, APS, ref. 177,
Wiley, and ref. 156, ACS.
Review article

a Fracture energy and fatigue threshold versus stiffness

III III
105 104

II II IV

Fatigue threshold Γ0 (J m–2)

Fracture energy Γ (J m–2)

104 103
IV

103 I
I 102

102
101

101

100
100
10–1 100 101 102 103 104 105 106 107 10–1 100 101 102 103 104 105 106 107
Modulus (kPa) Modulus (kPa)

b Fracture energy and fatigue threshold versus strength

106
104

10 5
II
Fatigue threshold Γ0 (J m–2)
IV III
Fracture energy Γ (J m–2)

IV III 103
104
II

103 102
I
I
10 2

101
101

100
100

10–1 100 101 102 103 104 105 106 10–1 100 101 102 103 104 105
Strength (kPa) Strength (kPa)

c Fatigue threshold versus fracture energy

I: Elastic hydrogels II: Viscoelastic hydrogels

104
Simple network PAAm Physical network–PAAm DN
II
Highly entangled PAAm PA
Fatigue threshold Γ0 (J m–2)

III
103 Tetra-PEG Coordination interaction
IV Protein/polypeptide crosslinked PAAm Dynamic covalent bond
PAMPS–PAAm DN Hydrophobic interaction
I
102 Hydrogen bonding
III: High-order structure
Phase separation PA IV: Bio-tissues
101
Phase separation PMMA–PAAc
Bio-tissues
Crystal PVA
Crystal PEG
100
Salt-out PVA
100 101 102 103 104 105 106
2D PVA–GO
Fibre-reinforced hydrogel
Fracture energy Γ (J m–2)

Fig. 4 | Fracture energy and fatigue threshold versus elastic modulus and topological network26,51–53,181,202,203 and double network (DN)49,50 (I). Viscoelastic
strength of hydrogels fabricated by various strategies. a, Fracture energy hydrogels with dynamic bonds42,54,55,58,71,133,140,180,197,204–206 (II). Hydrogels containing
and fatigue threshold versus elastic modulus. b, Fracture energy and fatigue high-order structure18,27,42,47,58,59,62,64,65,145,150,166,182,207,208 (III). Load-bearing bio-
threshold versus strength (engineering fracture stress). c, Fatigue threshold tissues5,209 (IV). GO, graphene oxide; PA, polyampholyte; PAAm, polyacrylamide;
versus fracture energy. Elastic hydrogels including simple network6,201, PEG, polyethylene glycol; PVA, polyvinyl alcohol.

independent of chemical crosslinking density but slightly dependent scales of nanometres, tens of nanometres and hundreds of nanometres,
on the chemical structure of the monomeric units41,42. The hierarchical respectively, play a crucial role in achieving exceptional mechanical
structures, including the transient network due to dynamic bonds, the properties (λf up to ~35, modulus up to ~2 MPa, strength up to ~4 MPa,
primary network, and the bicontinuous phase networks, which exist at self-healing capability up to 90%, and fracture energy up to ~4 kJ m−2)

Nature Reviews Materials

Review article
through multistep energy dissipation40. The hierarchical structures in
PA gels also contribute to excellent mechanical adaptation to cyclic train-
ing139. The value of λf is very close to the theoretical maximum stretch
ratio λmax predicted from the average network structure, suggesting that
such PA hydrogels have a defect-insensitive length ξ much larger than
the mesh size of the primary network. The small-strain moduli, large
deformation energy dissipation, and fracture energy of PA gels not only
obey the time–temperature superposition principle87, but also obey the
time–salt superposition principle, where salt ions screen the ionic bond-
ing between polyampholytes, accelerating the dynamic processes like
the temperature, and the dynamic mechanical behaviour for different
salt concentrations can be shifted onto a single master curve using salt-
concentration-dependent shift factors for the frequency140–142. Through
time–salt superposition, one can access a wide range of timescales that
are difficult to access at room temperature.
Microcrystals and microfibres. Hydrogels containing microcrys-
tals and microfibres typically have coexisting swelling (amorphous)
and deswelling (crystalline or fibre) domains (Fig. 3b). Because water
weakens polymer–polymer interactions, special strategies are required
to introduce microcrystalline domains or fibrils into hydrogels. Com-
mon strategies include freeze–thaw143, mechanical stretching144, sol-
vent exchange145, thermal drawing and rapid quenching146, and salting
out18,147,148. The formation of microcrystals can suppress crack propa-
gation because the crystalline domains have high chain density, and
the energy for rupturing a crystalline domain is higher than that for
rupturing the amorphous polymers5. Meanwhile, under loading, micro-
crystals convert to fibrils149, which are highly anisotropic and prone to
crack deflection. For example, freeze–thawing and air-drying resulted
in polyvinyl alcohol (PVA) hydrogels with high crystallization, which
showed superior crack resistance and therefore superior mechanical
properties150. Combining freeze-casting and salting out led to the PVA
hydrogels with a highly anisotropic hierarchical structure, consisting
of micrometre-scale honeycomb-like pore walls and interconnected
nanofibril meshes18. This anisotropic hierarchical structure contributes
to the suppression of crack propagation, leading to superior mechanical
performances (σf = 23.5 MPa, λf = 30, Г = 170 kJ m−2 and Г0 = 10.5 kJ m−2).
Strain-induced crystallization. Similar to natural rubber151–153, water-
containing hydrogels reinforced by strain-induced crystallization
have also been developed. Strain-induced crystallization can serve
as a damage-free reinforcement strategy for slide-ring PEG hydro-
gels with reduced slidable crosslinker hydroxypropyl-α-cyclodextrin
rings15. Because the crosslinks can slide along the PEG chains, the
initially amorphous polymer strands between the crosslinks can
become long and uniformly stretched under large deformation,
resulting in highly oriented PEG chains. Microcrystals form and melt
with elongation and retraction, respectively. Consequently, the crack
resistance during loading is substantially enhanced, resulting in a
fracture energy Г of up to 3.6 kJ m−2, much higher than gels with fixed
crosslinker or non-strain-induced crystallization systems (Г from about
0.05 to 0.24 kJ m−2).
Bilayer lamellar structure. The unidirectionally aligned hydrophobic
lamellar bilayers embedded in simple hydrophilic networks lead to
hydrogels with coexisting swelling and deswelling layers. A unique
example is anisotropic photonic poly(dodecyl glyceryl itaconate)/
polyacrylamide (PDGI/PAAm) hydrogels, which consist of macroscopic,
single-domain, periodical stacking of integrated microscopic lamellar
Nature Reviews Materials
bilayers (PDGI) inside the polymer matrix (PAAm)154,155 (Fig. 3b). Owing
to the water-impermeable nature of the hydrophobic bilayers, these
hydrogels show 1D swelling, anisotropic molecular permeation and
diffusion, and substantial mechanical anisotropy along the thickness
and in-plane directions. The rigid PDGI lamellar layers, having a lipid-
like mobile nature, act as reversible sacrificial bonds that disassociate
during deformation, thereby contributing to substantial energy dis-
sipation. Furthermore, at large deformation, the single-domain PDGI
lamellar bilayers transform into a hierarchical fibrous structure con-
sisting of micrometre-thick fibre bundles made from nanometre-thick
fibrils, which impedes crack growth and results in crack blunting156,157.
Therefore, the hydrogels exhibit large hysteresis, high strength and
extensibility, and extraordinary toughness. Lamellar hydrogels are
often called photonic hydrogels because they usually exhibit structural
colours due to Bragg’s reflection on the multilayer planes. The colours
can be dynamically tuned over a broad spectral range, spanning from
the ultraviolet–visible region to the near-infrared region, by tuning the
hydrogel layer thickness through the application and release of stress
or strain. Therefore, these tough gels could be used as stress or strain
sensors and deformation-based colour displays. Various chemical
structures have been incorporated into the soft layers to achieve differ-
ent functionalities. For instance, PDGI–h-PAAm (partially hydrolysed
PAAm) hydrogels have ultrafast colour response over the whole visible
wavelength158, and PDGI–PAAcNa (sodium polyacrylate) hydrogels
show colour tunability under perpendicular or parallel electric fields
in the directions of the hydrogel layers159.
Organic–inorganic nanocomposite. Polymer networks that are physi-
cally adsorbed on hard inorganic nanoparticles160–162, nanotubes163,164 or
nanosheets17,67,165,166 form one type of organic–inorganic nanocompos-
ite. The inorganic components act as a high-energy phase to toughen
the hydrogel167–169 (Fig. 3b). To achieve superior mechanical perfor-
mances in the water-equilibrated state, one should choose a hydrogel
showing deswelling behaviour or containing crystalline structure as
polymer matrix to enhance the interfacial affinity166, or the polymer
matrix should be post-crosslinked after the formation of a strong inter-
face between the polymer and the inorganic components170. Otherwise,
the swelling mismatch between the polymer network and inorganic
components weakens the load-transfer interface. Such nanocomposite
gels with a swelling mismatch in organic–inorganic components have
superior performance in the as-synthesized state (usually σf > 0.1 MPa,
λf > 10 and Г > 2 kJ m−2 for an appropriate amount of polymer and
inorganic components)17,171–173, whereas their mechanical properties
become weak at the swollen equilibrium state174.
Fibres and fibre-woven fabric composite. Incorporating macroscale
stiff fibres or fibre-woven fabrics into hydrogels is a powerful strategy
for fabricating strong and tough composites (Fig. 3b). This strategy
relies on two key principles62,175: strong interface adhesion between the
fibres or fabrics and the soft matrix to effectively disperse stress at the
crack tip; and a large modulus contrast between the stiff fibres or
fabrics and the soft hydrogel. The load-transfer length lT of unidirec-
tional fibre-reinforced soft composites correlates with the modulus
contrast between the fibre and matrix, lT ≈ EfAf /μm , where Ef is the
Young’s modulus of the fibre, μm is the shear modulus of the matrix,
and Af is the cross-sectional area of a fibre176,177. Along this line, polymer
fibres have been introduced into swelling hydrogels63,178. To achieve
good adhesion and load transfer between the matrix and polymer
fibres, covalent bonds were used for interlinking62. Such composite
Review article

a Cyclic fatigue measurement

L0
Elastic gel
C0 Cyclic to
H0 steady state

∆c/∆N
Gel with
Undeformed state
hierarchical
structure
1st cycle
N cycles

Stress (MPa)
N=1 2 … 0
λm c G0 Gtran G
… Nth cycle

1 New surface
Time W(λm) λm

λ G0: Fatigue threshold Γ0 = G0

G = W(λm) H0 Gtran: Slow-to-fast crack growth transition

b Fatigue resistance of elastic hydrogels c Fatigue resistance of viscoelastic hydrogels

Chemical crosslink Reversible crosslink

Cyclic Cyclic
loads loads
Chain Chain
scission scission

d Fatigue crack resistance by hierarchical structure

Phase separation Fibre

Polymer-dense phase Fibre Matrix

Cyclic Cyclic
loads loads

Polymer-sparse phase

Fig. 5 | Fatigue fracture measurement and the mechanisms proposed to the fatigue threshold G0 below which the crack does not grow. b, Chain scission
enhance the fatigue resistance of hydrogels. a, Pure shear test for cyclic mechanism for elastic hydrogels. c, Fatigue resistance of viscoelastic hydrogels.
fatigue test. From the fatigue resistance curve (Δc/ΔN versus G), one can obtain d, Fatigue resistance enhanced by high-order structures.

hydrogels showed a certain reinforcement in the as-synthesized state,
but were rarely used in water equilibrium state, since swelling resulted
in weak mechanical performance owing to stress mismatch between
the hydrogel matrix and the fibres. Using deswelling hydrogels to
form the fibre-reinforced hydrogels is a more successful strategy. For
example, composites obtained from glass fibre-woven fabric and poly-
ampholyte hydrogels show exceptional mechanical performance with
a superior tearing strength of 380 N mm−1, a tensile modulus of 606 MPa
and a fracture energy of 250 kJ m−2, which are several orders of magni-
tude greater than individual neat materials44,179. Such excellent mechan-
ical properties stem from the strong physical adhesion of the deswelling
polyampholyte matrix to the negatively charged glass fibre surface in
water as well as from the high viscoelastic energy dissipation density
of the polyampholyte matrix.
Fatigue resistance of hydrogels
Long-term mechanical stability under prolonged cyclic loads is extremely
important for tough hydrogels to emulate load-bearing biological tis-
sues, such as muscles and cartilage, that are constantly undergoing
reciprocal cycles in daily life. An early study on the fatigue of hydrogels
was reported in 2017 (ref. 6). Fatigue damage occurs when a sample is
subjected to irreversible changes in mechanical properties under cyclic
loading92. Fatigue is usually characterized by two aspects: the critical
energy release rate G0 for a pre-existing crack to grow, and the crack
growth rate per cycle (dc/dN) versus the energy release rate G of cyclic
loading180 (Fig. 5a). Typically, a sample with a pure shear or single-edge
notch geometry is used for cyclic fatigue tests. In an example of pure
shear geometry (Fig. 5a), a pre-notch perpendicular to the loading direc-
tion is made at the middle edge of the sample. At a certain loading

Nature Reviews Materials

Review article
amplitude (λm) and cycle period (or speed), the crack length c grows
above a certain energy release rate G, and c increases gradually with
number of cycles N. The energy release rate can be obtained from
the stress–stretch curve of the corresponding unnotched sample at the
λ
same loading condition, by G = W(λm)H0, where W (λ m) = ∫ m σ dλ is
1
the strain energy when the cyclic loading curve reaches steady state,
and H0 is the initial sample height along loading direction. From the
crack growth rate per cycle versus the energy release rate, one obtains
the fatigue-resistant curve and the fatigue threshold Г0 = G0 (dc/dN → 0)
below which the crack does not grow (infinite lifetime). A comparison
of Г0 between synthetic hydrogels (including elastic, viscoelastic hydro-
gels and hydrogel containing high-order structures) and bio-tissues is
presented in Fig. 4. When comparing Г0 among different materials, atten-
tion should be paid to the observation resolution of the fatigue thresh-
old. Г0 is denoted as the threshold below which crack growth is
undetectable at the camera resolution under certain fatigue cycles.
a Force-induced mechanical activation of dibromocyclopropane mechanophores
O O
Br
Br Stress activation
TBA SA
Crosslinking
Br Br
Closed Open
Stress activation and
chain scission
b Force-induced radicals in DN gel
C C
or
N N
Force
R
R
Fig. 6 | Strategies proposed for mechanochemical strengthening and
self-growing hydrogels. a, Self-strengthening through ring-opening reaction
of gem-dibromocyclopropanes and subsequent crosslinking by nucleophilic
displacement reactions with TBA SA (ditetrabutylammonium salt of sebacic
acid). b, Force-induced mechanoradicals in double-network (DN) gel, which can
Nature Reviews Materials
The observation resolution of several representative hydrogels is listed
in Table 1.
Fatigue-resistant behaviour of elastic hydrogels. Currently, the
fatigue mechanisms in hydrogels are mainly explained by rubber elastic
theory92. The fatigue threshold Г0 of a single-network hydrogel fol-
lows the chain scission mechanism (Fig. 5b), that is, the Lake–Thomas
model (equation (8)), which was also confirmed in tetra-PEG gels with
a relatively homogeneous network structure181. Therefore, increasing
Nx in simple network hydrogels is an effective strategy to improve Г0.
However, a large Nx results in small elastic modulus E (ref. 92). To solve
the issue, fatigue-resistant hydrogels that use tandem-repeat pro-
teins (polyproteins) as crosslinkers and coiled PAAm for percolating
networks were developed53. During cyclic fatigue tests, the folda-
ble polyprotein crosslinkers around the crack tip unfold, yielding a
fatigue threshold (Г0 = 126 J m−2) that is substantially superior to that of
Br
8
O O O
8 O
O O
Br
Crosslinking
c Force-induced cyanofluorene radicals to initiate the polymerization of side chains
Physical
crosslinking
Force
induce polymerizing monomers to reconstruct and strengthen the network.
Compared with the first network crosslinked by strong C–C bonds, the weak
azoalkane crosslinked first network can produce more mechanoradicals in DN
gels. c, Force-induced cyanofluorene radicals to initiate the polymerization of
side chains. Panel a adapted from ref. 185, Springer Nature Limited.
Review article

a Force-induced self-growth and reinforcement

Mechanical stress Rest First network Open system

(rigid and brittle)
Second network
(soft and stretchable)
1st cycle
4 2nd
3rd
3 4th

F (N)
Covalent bond 2
Destruction Reconstruction
R• •R scission
1
R• Mechanoradical

Newly formed 0
network 15 30 45 60 75 90
Monomers L (mm)

b Sustainable mechanochemical growth supported by vascular-like perfusion through the inner channel

Blood vessel

Circulatory system Channel

Nutrients Pump

Chemicals

F F
Jig
Destruction
Luer lock 1st cycle 60 min
R· ·R 5 min 120 min
20 min 360 min
Reconstruction Repeat
5
Tensile deformation

4
Complement

3
F (N)

Flow
2

PNaAMPS network PAAm network 1

R · Mechanoradical Chain fracture
Monomer 0
Diffusion New network
0 15 30 45 60 75 90 105
Dp (mm)

c Force-triggered rapid microstructure growth on surface

d
Indenter

Monomer solution
Force Microstructure H Vertical pattern Horizontal pattern Smooth surface
stimuli growth
Gel surface
F Lmax D
TDN
Gel bulk
g
1 mm 1 mm 1 mm
θrec = 15° θrec = 12° θrec = 20°
F F g

Double network Chains scission in process zone New polymer chain growth θadv = 42° θadv = 50°
θadv = 30°
500 µm 500 µm 500 µm

First network Second network Monomer Mechanoradical Newly formed

(brittle) (stretchable) polymer chain

Nature Reviews Materials

Review article
Fig. 7 | Force-induced self-growing and strengthening in DN hydrogels.
a, Self-growing and strengthening of double network (DN) hydrogel
through rupturing the first network to produce radicals and subsequent
polymerization to reconstruct network. F is force and L is sample length.
b, Sustainable mechanochemical growth of channel-containing DN gel
under cyclic training. The channel can supply monomers for polymerization
PAAm hydrogel crosslinked by bisacrylamide (Г0 = 7.5 J m−2), which has
about half the modulus of the polyprotein crosslinked PAAm. Induc-
ing highly entangled polymers into single-network elastic hydrogels
is another strategy to improve Г0. For instance, PAAm hydrogel with
dense entanglements fabricated through a high concentration of PAAm
and sparse crosslinks has high modulus (0.1 MPa) and Г0 (200 J m−2)26.
The sparse chemical crosslinks impeding the disentanglement of
polymer strands contribute to the high modulus, and the dense entan-
glements allowing the transmission of tension in the polymer strands
at the crack tip to other strands contribute to the fatigue threshold.
As a special type of elastic material, chemically crosslinked DN
hydrogels can resolve the conflict between Г0 and E (refs. 49,50). The
high elastic modulus and robust fatigue resistance are ascribed to
the densely crosslinked first network and sparse second network,
respectively. During cyclic fatigue tests, the first network fractures
into small fragments, effectively serving as mobile crosslinks for the
second network, which features long strands (large Nx). Consequently,
DN hydrogels with loosely crosslinked second networks can achieve
a fatigue threshold of up to 400 J m−2 with a high Young’s modulus of
0.3 MPa while still containing around 90 wt% water.
Fatigue resistance of viscoelastic hydrogels containing dynamic
bonds or weak crosslinking. Although dynamic bonds substantially
enhance the toughness of viscoelastic hydrogels, they contribute little
to the fatigue threshold. The dynamic bonds are gradually destroyed
under cyclic loading, and the fatigue threshold of such tough hydrogels
also follows the chain scission mechanism described by the Lake–
Thomas model (Fig. 5c). For example, Ca2+-alginate/PAAm hydrogels
with interchain ionic bonds have a high fracture energy of several kilo-
joules per square metre but a low Г0 of 35 J m−2, which is close to the
corresponding Na+-alginate/PAAm without interchain ionic bonds133.
Nevertheless, the presence of dynamic bonds does reduce the crack
growth rate above Г0. Notably, whether dynamic bonds contribute to
gel Г0 depends on the observation timescale relative to the relaxation
time of the hydrogel. By extending the observation timescale of PA gels
by the time–salt superposition principle140,141, Г0 was observed to be rate
independent and matched the predicted value from the Lake–Thomas
model only when the fatigue test was performed at a strain rate in the
elastic regime. By contrast, Г0 increased with increasing the strain rate
ε ̇ (Г0 ~ εν̇ with scaling parameter 0 < ν < 0.27) when the fatigue test was
performed in the viscoelastic regime140. Thus, the fatigue threshold can
be improved by tuning the sacrificial bond dynamics of the viscoelastic
hydrogels. Similar to dynamic bonds, weak side-chain crosslinks are
also gradually destroyed under cyclic loading. Triggering the rupture
of weak side-chain crosslinks using force can lengthen the bridging
strands around the crack tip, improving the fatigue threshold108.
Fatigue resistance improved by high-order structure. Introducing
high-order structures, such as microphase separations42,58–60, micro-
crystals145,150, fibrils18,47,61,62,64,182,183 and nanocomposites66,67 into polymer
networks can substantially improve the fatigue resistance of hydrogels.
Nature Reviews Materials
and water for avoiding sample dry. c, Microstructure growth on DN
hydrogel surface via force-induced self-growing strategy. θadv, advancing
angle; θrec, receding angle; Dp, displacement; PAAm, polyacrylamide; PNaAMPS,
poly(2-acrylamido-2-methyl-1-propanesulfonic acid sodium salt). Panel a
reprinted with permission from ref. 72, AAAS. Panel b reprinted with permission
from ref. 187, RSC. Panel c reprinted from ref. 188, CC BY 4.0.
Rather than the nanometre-scale polymer chains, the large-scale stiff
constituents are broken to advance the crack during cyclic loading.
Therefore, the intrinsic energy required to advance the crack per unit
area equals the covalent energy of a layer of the reinforcement con-
stituents per unit area. The Lake–Thomas model can be generalized as
Г0 = LNU (refs. 183,184), where L is the size of reinforcement constituents,
N is the number of the reinforcement constituents per unit volume, and
U is the energy required to break the reinforcement constituents. Com-
pared with typical hydrogels without reinforcement components, L can
be increased by two to eight orders of magnitude, and U can be increased
by fourteen orders of magnitude184. Meanwhile, N can be adjusted within
a broad range. As a consequence, Г0 can be enhanced by two to four
orders of magnitude. These hydrogels show fracture energy and fatigue
thresholds comparable to or even better than bio-tissues (Fig. 4).
Hydrogels with hierarchical structures may exhibit multilevel
fatigue resistance compared with elastic hydrogels, which is derived
from the minor slope of the curve of dc/dN versus G (Fig. 5a). For exam-
ple, hierarchical PA gels that include ~0.1-nm ionic bonds, ~10-nm
primary polymer network, and ~100-nm bicontinuous phase network
structures (Fig. 5d) exhibit multilevel fatigue-resistant behaviour42,58,140.
The fatigue threshold Г0 is mainly correlated with the mesh size of the
primary polymer network bridged by both chemical crosslinking and
trapped entanglement. Above Г0, a transition point Gtran marking the
jump from slow to fast crack growth occurs in PA gels with strong phase
separation. Gtran is correlated to whether the damage occurs in the hard
phase network. Fatigue fracture is delayed to a larger Gtran when there is
a bigger phase contrast, whereas gels without phase separation exhibit
only a fast crack growth mode (without Gtran).
Microcrystalline domains are comprised of densely folded chains.
Pulling out the polymer chain from a microcrystalline domain needs
energy multiple times what is needed to fracture a single polymer
chain. In addition, mechanically rupturing the microcrystalline domain
demands energy several times that required to rupture the correspond-
ing amorphous polymers61. Therefore, microcrystalline domains act as
intrinsic high-energy phases. For example, the introduction of micro-
crystalline domains into amorphous PVA hydrogels using a freeze–
thawing and air-drying approach enhanced the fatigue threshold from
10 to 1,000 J m−2 (ref. 150). Meanwhile, the elastic modulus of such PVA
hydrogels can reach 10 MPa, effectively resolving the tradeoff between
modulus and fatigue threshold. Similar to microcrystals, fibres62–64,182
can act as strong barriers to fatigue crack extension, resulting in a high
fatigue threshold (Г0 > 1 kJ m−2), especially when the fibres are aligned
perpendicular to the crack extension direction (Fig. 5d).
Mechanochemical strengthening and self-growing hydrogels
Living soft tissues possess the remarkable ability to autonomously grow,
remodel and strengthen themselves in direct response to mechanical
forces. For instance, skeletal muscles can increase in mass and strength
when subjected to cyclic training. There has thus been increasing interest
in developing self-growing and self-strengthening polymer networks
based on force-triggered mechanoradical generation and subsequently
Review article
induced chemical reactions. Mechanical forces typically cause bond
scission in hydrogels, resulting in material failure. These mechano-
radicals, in turn, initiate processes such as crosslinking or polymeriza-
tion propagation, effectively converting mechanical energy into an
increase in material strength (Fig. 6). Force-induced crosslinking was
pioneered by the application of shear forces to trigger the ring opening
of gem-dibromocyclopropanes to generate allylic bromides, which were
subsequently crosslinked through nucleophilic substitution reactions
with a bifunctional carboxylate185 (Fig. 6a). The mechanically triggered
crosslinking outcompetes the destructive shearing forces, resulting in
an increase in the material’s modulus by several orders of magnitude.
In 2019, a ‘self-growing’ strategy was introduced that relies on force-
induced mechanoradical generation and subsequent polymerization
within DN hydrogels72. The densely crosslinked initial brittle network
undergoes ruptures when subjected to loads, concurrently generating
mechanoradicals (Fig. 6b). These mechanoradicals then initiate the
polymerization of monomers, forming a new polymer network. This
process, similar to open and dynamic biological systems186, leads to
an increase in the mass of DN gels under repeated mechanical loading
through structural destruction and reconstruction with a sustained
monomer supply, substantially strengthening the DN gels72 (Fig. 7a). By
constructing a vascular-like circulatory system to supply monomers to
channel-containing DN gels, sustainable self-growth of hydrogels in air
was achieved187 (Fig. 7b). The force-induced self-growing strategy within
the DN gel system allows for local remodelling and for the creation of
microstructures on the hydrogel surface on demand188, which provides a
facile way to imbue the hydrogel surface with specific properties, such as
wettability and cell adhesion (Fig. 7c). In such systems, the active mecha-
noradical concentration plays a crucial role on the reconstruction of the
ruptured network. DN hydrogels are unusual mechanochemical materi-
als, as numerous mechanoradicals are generated by the internal fracture
of the brittle first network. The efficiency of the mechanoradical genera-
tion can be further increased by using weak azoalkane crosslinkers in
the first network, as the C–N=N bond (azo group connected to saturated
carbon atoms) in azoalkane has a lower bond dissociation energy than
the saturated C–C and C–N bonds in traditional crosslinker189 (Fig. 6b).
In common soft materials comprising a single network, the
breaking of covalent bonds often leads to the failure of the entire
material. Therefore, weak moieties (for which bond dissociation
energy is lower than that of the C–C bond), such as difluorenylsuc-
cinonitrile190, diselenide191 and disulfide192,193, have been introduced
into soft materials to achieve mechanoradical-induced self-growing
and strengthening (Fig. 6). In polyurethanes, for example, the dis-
sociation of weak difluorenylsuccinonitrile moieties in the main
chains190 (Fig. 6c) resulted in the production of pink cyanofluorene
(CF) radicals. These CF radicals initiated the polymerization of side
chains with methacrylate groups, leading to new chemical crosslink-
ing in the network. Therefore, the modulus increased markedly with
increasing mechanical stimuli cycles. Additionally, the generated CF
radicals displayed notable resilience to oxygen exposure, making this
approach well suited for applications in ambient air conditions. This
strategy simultaneously incorporates damage reporting (a pink colour
appears, owing to the generation of CF radicals) and strengthening
capabilities.
Conclusions and outlook
Since the 2000s, various successful designs for tough hydrogels have
been proposed, strengthening the position of hydrogels as promis-
ing soft and wet materials for diverse applications, especially in
Nature Reviews Materials
biomedical fields. However, challenges in fundamental science and
engineering still limit their real-life applications. From the fundamental
point of view, cutting-edge fracture mechanics theories were developed
for nonlinear elastic materials, which assume no strain-rate depend-
ency. However, hydrogels with dynamic bonds are strongly strain-rate
dependent, like most biological tissues. Moreover, hydrogels with
relatively strong dynamic bonds show loading-history dependence,
resulting in richer and more complex mechanical behaviours. New
theories and experimental approaches are required to understand
the toughening and antifatigue mechanisms related to such nonlinear
viscoelastic effects. Resulting progress in understanding the dynamic
aspect of the materials and the molecular mechanisms should assist in
the design of new structures in material development.
From an engineering point of view, developing hydrogels with
comprehensive mechanical properties that match those of specific
biological tissues is indispensable. Currently, loading-induced sof-
tening, substantial stress relaxation, and large hysteresis loops are
the main mechanical characteristics of tough hydrogels. Introducing
protein-like intrachain folded structures into hydrogels may be a future
strategy to create hydrogels with fast hysteresis recovery. Moreover,
one needs to address issues related to biocompatibility and biochemi-
cal stability in vivo, ensuring that implanted hydrogel artificial tissues
can maintain their structure and functionality. Because hydrogels are
an open system, when hydrogels are implanted into the body they may
interact with various minerals and biomolecules during prolonged use.
Using biopolymers as constituents or designing copolymers possessing
monomer sequences that feature amino acids from functional proteins
could be possible strategies to solve this issue. For the latter, molecular
design, notably through machine learning from protein structures, and
precise control of the designed monomer sequences are key challenges.
Tough hydrogels bring new opportunities beyond their load-
bearing use. Because they are open systems and can be permeated by
small molecules, tough hydrogels are promising as force-catalysing
materials that use mechanical energy to drive chemical reactions. As a
proof of concept, tough DN hydrogels could enable the development
of mechanochemical-based metabolic-like active materials. These
new materials could achieve functions such as self-strengthening,
self-growth or morphogenesis by supplying specific monomers dur-
ing mechanical loading. To develop such adaptive materials — whose
structure undergoes repeated destruction and reconstruction under
load — challenges include the removal of the destroyed residuals and
the maintaining of the internal fracture characteristics of the DN that
are essential for material regeneration after many loading cycles. For
the former, using a reversible chemical reaction pathway could be a
solution, whereas for the latter, a fundamental understanding of the
mechanisms of internal destruction and reformation is key. Exploring
this new field of soft materials will require interdisciplinary research in
fracture mechanics, polymer physics and polymer chemistry.
Published online: xx xx xxxx
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Acknowledgements
This work was supported by JSPS KAKENHI (grant nos. JP22H04968, JP22K21342, JP22K20521
and JP23K13796).
Author contributions
Both authors contributed to the discussion, writing, reviewing and editing of the manuscript.
Competing interests
The authors declare no competing interests.
Additional information
Supplementary information The online version contains supplementary material available at
https://doi.org/10.1038/s41578-024-00672-3.
Peer review information Nature Reviews Materials thanks Kozho Ito; Shaoting Lin, who
co-reviewed with Zhaohan Yu; and the other, anonymous, reviewer(s) for their contribution
to the peer review of this work.
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