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Du et al. Soft Sci 2024;4:35 https://dx.doi.org/10.20517/ss.2024.31 Page 9 of 23

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management, where high precision is essential . The integration of these unique properties with modern
electronic technology broadens the application scenarios for hydrogels, offering promising prospects for the
development of intelligent medical systems that integrate monitoring, diagnosis, and treatment.

Other hydrogel actuators
Ingestion
Oral administration is the most common method of drug delivery due to its convenience, non-invasiveness,
and low cost. However, the harsh digestive environment of the gastrointestinal tract and the transport
limitations of the gastrointestinal mucosa significantly affect drug absorption, particularly for biological
agents . Additionally, drugs administered orally have longer transport times and slower onset. Hydrogel
[88]
actuators, which respond to external stimuli by swelling, can enter the gastrointestinal tract orally, shrink
into a dense state to protect encapsulated drugs, and ensure targeted release at specific locations . This
[89]
approach also slows down the release rate, preventing premature drug release before reaching the target site.
Some hydrogel actuators can quickly absorb gastric juice and respond to pH changes, minimizing damage
[90]
to gastric wall cells . Stimuli-responsive hydrogel actuators provide an effective means for treating
gastrointestinal diseases, enabling a broader range of drugs to be used. Moreover, these systems can achieve
gastrointestinal residence by utilizing pH or enzyme differences in the gastrointestinal environment for
controlled, targeted drug release. Continuous and stable drug release during the treatment period improves
drug efficacy. Therefore, hydrogel actuators are an excellent choice for oral drug delivery. By adjusting
various parameters, hydrogels can be tailored for different physiological conditions, offering broad
application prospects in the treatment of gastrointestinal diseases.

Injection
Compared to conventional implantable hydrogel actuators, injectable hydrogel actuators respond more
easily to various stimuli and avoid frequent invasive surgeries, offering a novel approach for chronic disease
[19]
treatment . In drug delivery, hydrogels are excellent carriers due to their high water content and
biocompatibility. Unlike traditional injectable drug methods, injectable hydrogels provide local,
controllable, and continuous drug delivery . Injectable hydrogels should be in a low-viscosity sol state
[91]
before injection, and then gelate and cross-link through various chemical or physical interactions post-
injection. Subsequently, the hydrogel should undergo gradient absorption and degradation, ensuring the
byproducts are non-toxic . Additionally, injectable hydrogels can dynamically adjust in response to
[92]
different external stimuli, tailored to specific disease treatments. Among various stimuli-responsive modes,
temperature and electrical stimuli are the most effective. Temperature-responsive hydrogel actuators can
transition from liquid to solid as ambient temperature changes from room temperature to body temperature
during injection. This allows drugs to be loaded into the hydrogel in a liquid state and continuously released
at the target site once the hydrogel solidifies in the body. During wound healing, increased inflammation
raises wound temperature, causing the hydrogel actuator to change volume and increase drug release at the
wound . Electrical stimulation is easier to produce and control compared to other stimuli-responsive
[5]
modes, despite the poor degradability of conductive polymers.

Implantation
Implantable hydrogel actuators can be used for the diagnosis and treatment of various diseases. The
implanted hydrogel exhibits stable mechanical properties, and its physical and chemical structure helps to
minimize immune responses, provide a stable microenvironment, and ensure long-term retention at the
target site. This stability enhances the effectiveness, reliability, and continuity of treatment . The hydrogel’s
[63]
intrinsic properties allow it to mimic the mechanical and biochemical characteristics of human tissues,
resulting in reduced nonspecific binding to interfering molecules and lower background signals. Flexibility,
biodegradability, and non-toxicity are critical parameters of hydrogel actuators. As hydrogel technology