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Du et al. Soft Sci 2024;4:35 https://dx.doi.org/10.20517/ss.2024.31 Page 17 of 23

[13]
Therefore, targeted local treatment is a more appropriate approach .

Huai et al. developed an alginate/hyaluronic acid hydrogel that responds to the colonic
[106]
microenvironment [Figure 6A]. This hydrogel demonstrates well-controlled drug release and significant
biodegradability in inflammatory environments, minimizing early drug leakage in the gastrointestinal tract.
Its mucosal adhesion and pH-sensitive properties enable targeted drug delivery and release at inflamed sites,
allowing for smaller drug doses to achieve the same therapeutic effect. Therefore, this hydrogel holds
promise as a novel oral antibody delivery system.

Wang et al. developed an intestinal enzyme-responsive hydrogel encapsulating the model drug imatinib for
long-term controlled drug release and treatment of bowel cancer through oral administration
[107]
[Figure 6B]. The drug-loaded hydrogel responds to intestinal enzymes, triggering hydrolysis and subsequent
drug release, significantly enhancing the tumor suppression effect of the model drug. Experiments show
that this enzyme-responsive hydrogel can achieve the long-term synchronous release of kinase inhibitors
(imatinib) and promoters (sodium deoxycholate) in the intestine, improving therapeutic efficiency. This
method provides an effective way to enhance the bioavailability of oral hydrophobic anticancer
chemotherapeutic drugs.

There are significant differences in conditions such as pH values or enzyme types in different parts of the
gastrointestinal tract. Therefore, hydrogel actuators for treating gastrointestinal diseases should have more
precise and sensitive responsive characteristics.

Neuromodulation
Implantable neural modulation devices, such as deep brain stimulators and vagus nerve stimulators, have
been widely used to treat neurological disorders [125,126] . These devices are often made from rigid probes and
are limited by lower sensitivity and mechanical compatibility with tissue. Reducing the mechanical
mismatch at the electronics-tissue interface can significantly reduce adverse immune responses caused by
chronic implantation [127,128] . Recent developments in soft elastic hydrogel materials have further enhanced
the ability for localized low-voltage neural modulation, and they exhibit good biocompatibility and
mechanical interface compatibility .
[81]
Liu et al. reported elastic microelectronics composed of a highly conductive hydrogel and an elastic
fluorinated photoresist as a passivation insulation layer. The microelectronics has 10 kPa Young’s modulus
and a current injection density 30 times higher than platinum electrodes. Effectiveness has been validated by
applying electrical stimulation to the mouse nerve [Figure 6C]. Tringides et al. proposed a conducting
[129]
supersoft viscoelastic hydrogel filled with carbon nanomaterials. This array is primarily made from
hydrogels with highly tunable physical properties, allowing for independent variation of viscoelasticity and
stiffness. It can be used for neural signal acquisition and electrical stimulation [Figure 6D]. Yang et al.
[130]
report a strategy for the construction of conductive and bioadhesive hydrogel neural interfaces with
photopatternable, antifouling, soft, and elastic features. The prepared multifunctional hydrogel can achieve
rapid adhesion and more stable electrical integration on moist tissues and has shown effectiveness in the
electrical signal recording and stimulation of the rat sciatic nerve [Figure 6E].
[131]
For actual clinical applications, further improvements are needed to enhance the usability and durability of
implantable devices, while reducing potential immune responses in the biological system during long-term
implantation.