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Du et al. Soft Sci 2024;4:35 https://dx.doi.org/10.20517/ss.2024.31 Page 7 of 23

stimuli, the synergistic response performance of each stimulus is crucial. Compared to single stimuli-
responsive hydrogels, multiple stimuli-responsive hydrogels offer greater control over their behavior,
enhancing overall performance and applicability.

PROPERTIES OF HYDROGEL ACTUATORS
Stimuli-responsive hydrogel actuators possess high water content, mechanical strength, and
biocompatibility, enabling them to respond to external stimuli through phase or structural changes. Many
studies have demonstrated the feasibility of stimuli-responsive hydrogel actuators. In this section, we
summarize necessary characteristics of hydrogel actuators, and then discuss their applications in
therapeutics.

Characteristics of hydrogel actuators
Mechanical behavior
The high water content and porous structure of hydrogels give them a softness similar to that of native
tissue. Common parameters used to indicate the mechanical properties of hydrogels include stiffness,
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compressive strength, tensile strength, pore size, and toughness . Conventional stimuli-responsive
hydrogels often have weak mechanical properties, slow response times, and poor environmental tolerance,
which limit their applications in soft actuators. Constructing reversible non-covalent bonds, such as
hydrogen bonds, electrostatic interactions, and coordination bonds, can effectively enhance the mechanical
properties of hydrogel actuators. This improvement is crucial for increasing the toughness of hydrogels, and
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these reversible non-covalent bonds can also impart self-healing properties . Additionally, the crosslinking
method significantly affects the mechanical properties of hydrogel actuators. Typical chemical cross-linking
networks offer more stable and stronger mechanical properties, while physical cross-linking networks are
flexible, stretchable, and sometimes self-healing . Therefore, different crosslinking methods produce
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[40]
hydrogels with varying excellent physical and chemical properties . Some studies have shown that NP
doping and chemical cross-linking are also key methods to improve mechanical properties . The
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application of hydrogel actuators in different biomedical fields requires diverse mechanical properties. For
example, hydrogel stiffness is necessary for tissue matrix substitutes. Stiffness has been shown to affect cell
activity and function, ultimately achieving cellular and tissue homeostasis. Furthermore, the porous
structure is another vital feature of hydrogels, serving as transport channels for drugs and other substances,
regulating many physiological activities, and determining the effects of biomedical applications. Elasticity in
the interactions between hydrogel and tissue can regulate interactions with the surrounding matrix and may
lead to variations in cell diffusion.

Swelling performance
Swelling capacity is a crucial property for biomedical applications. The swelling properties depend on their
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pore size, internal network structure, and hydrophilic and hydrophobic characteristics . These properties
result in different swelling behaviors, categorized into high swelling, non-swelling, and negative swelling .
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For example, hydrophilic hydrogels with large mesh sizes are highly prone to swelling, whereas
hydrophobic hydrogels with a higher degree of crosslinking exhibit minimal swelling. The swelling
performance of hydrogels is crucial in the biomedical field, as it enables drug release, substance transfer, and
absorption of wound secretions. Hydrogels with varying swelling levels have distinct application prospects.
Hydrogels with high swelling properties are extensively used in wound healing and drug administration. In
contrast, non-swelling hydrogels are crucial in tissue adhesives and bioelectronics due to their ability to
maintain stable morphology and physical properties in physiological environments. Some hydrogels also
exhibit negative swelling, which can be utilized for non-invasive wound closure and drug release.