Fundamentals and Advances in Stimuli-Responsive Hydrogels and Their Applications: A Review

Abstract

This review summarizes the fundamental concepts, recent advancements, and emerging trends in the field of stimuli-responsive hydrogels. While numerous reviews exist on this topic, the field continues to evolve dynamically, and certain research directions are often overlooked. To address this, we classify stimuli-responsive hydrogels based on their response mechanisms and provide an in-depth discussion of key properties and mechanisms, including swelling kinetics, mechanical properties, and biocompatibility/biodegradability. We then explore hydrogel design, synthesis, and structural engineering, followed by an overview of applications that are relatively well established from a scientific perspective, including biomedical uses (biosensing, drug delivery, wound healing, and tissue engineering), environmental applications (heavy metal and phosphate removal from the environment and polluted water), and soft robotics and actuation. Additionally, we highlight emerging and unconventional applications such as local micro-thermometers and cell mechanotransduction. This review concludes with a discussion of current challenges and future prospects in the field, aiming to inspire further innovations and advancements in stimuli-responsive hydrogel research and applications to bring them closer to the societal needs.

Keywords: applications; biocompatibility; biodegradability; current challenges; future prospects; hydrogels; mechanical properties; stimuli-responsive hydrogels; structure engineering; swelling kinetics.

Figure 1

A schematic summary of the thermogelling behavior, illustrating the combined effects of multiscale thermoresponsive mechanisms, as well as the various applications of thermogels [65].

Figure 2

General working mechanism of pH responsive hydrogels [70].

Figure 3

Molecular structure and responses of a photo-responsive hydrogel (center) [27]: The photo-responsive groups (black) can be located in various regions: (1) at crosslinking points, (2) within the polymer or supramolecular backbone, (3) alongside chains, or (4) dissolved within the hydrogel’s aqueous medium. Depending on the position and nature of the photo-responsive group, photo-induced responses may include shrinking (A) and partial de-crosslinking (B), typically associated with increased water absorption and, thus, greater hydrogel volume. Conversely, photo-triggered crosslinking tends to result in hydrogel contraction. Complete de-crosslinking leads to hydrogel breakdown (liquification) (B)*. Additional hydrogel responses include (C) photothermal activation (localized temperature increase), (D) the activation or deactivation of reactive sites, and (E) substrate release or capture.

Figure 4

(a) Bright-field optical microscopy images of structures made from poly(NIPAAm₉₅-co-BPQAAm₅) are shown for the specified combinations of P_L and t_d, captured in dry air (bottom row) and in humid air to induce hydrogel formation (top row). (b) AFM images of the same poly(NIPAAm₉₅-co-BPQAAm₅) structures are presented at the interface between the bare gold substrate and the polymer layer, prepared under the following conditions: (I) P_L of 15 mW and t_d of 1 s; (II) P_L of 10 mW and t_d of 1 s; and (III) between two polymer network regions fabricated with P_L of 15 mW, t_d of 1 s, and P_L of 15 mW, t_d of 3 s. The scale bar represents 5 µm [93].

Figure 5

Temperature-controlled AFM measurements of Young’s moduli performed for a poly(NIPAAm₉₄-co-MAA₅-co-BPQAAm₁) hydrogel pad prepared using a laser power P_L of 10 mW and dwelling times t_d of 1, 3, and 5 s [93]. (a) A bright-field microscopy image shows the formed hydrogels and water condensation patterns after exposure to humid air. (b,c) Histograms display the measured Young’s moduli at 25 °C and 40 °C, respectively. The regions marked with blue and yellow rectangles in the microscopy image indicate the areas where the modulus distributions were analyzed.

Figure 6

(a) Schematic representation of the SPRi setup used for probing the pNIPAAm-based microstructures in air. (b) SPRi images of the microstructures. (c) Corresponding angular reflectivity spectra in air for poly(NIPAAm₉₅-co-BPQAAm₅) structures prepared with a constant dwelling time t_d = 3 s and varying laser power P_L = 5, 10, or 15 mW. The solid curves in (c) are fits calculated using a Fresnel-based reflectivity model [93].

Figure 7

Self-healing and self-adhesion performance of the MXene/PMN hydrogel [113]. (a) Photographs illustrating the self-healing process of the MXene/PMN hydrogel: (i) original state, (ii) after being cut, (iii) during the self-healing process, and (iv) stretched after self-healing. (b) A hook coated with MXene/PMN hydrogel. (c) The MXene/PMN hydrogel hook adhered to various surfaces: (i) glass, (ii) PET, (iii) metal, and (iv) porcine skin. (d) Self-adhesive strength of the MXene/PMN hydrogel on different substrates. (e) Repeatable self-adhesive behavior of the MXene/PMN hydrogel on various substrates. Reprinted from [113] with permission from Elsevier.

Figure 8

Plasmonically enhanced multiphoton polymer crosslinking (MPC) [126]: (a) AFM height topography image of the crosslinked polymer at the plasmonic hotspots with (b) respective cross sections for individual gold nanoparticle—polymer structure; (c) normalized transmission spectra of the plasmonically enhanced MPC-written poly(NIPAAm₉₄-co-MAA₅-co-BPQAAm₁) sample and schematics of the hydrogel swelling and collapsing at the plasmonic hotspots.

Figure 9

Wound-healing acceleration with 3D MSC spheroid-encapsulated hydrogel [165]. (a) Representative images of wounds in db/db mice treated with control (2D MSC without hydrogel), 2D MSC + hydrogel, and 3D MSC + hydrogel at weeks 0, 1, 2, and 3. (b) Wound closure areas were measured at weeks 1, 2, and 3. * p < 0.05, ** p < 0.01 versus control; ## p < 0.01 versus 2D MSC + hydrogel group.

Figure 10

(a) Schematic of magnetically steered swimming and terrestrial robots targeting tumors [82]. (b) Design and swimming behavior of a jellyfish-inspired soft millirobot [174]. The arrows indicate the directions of the external magnetic field.

Figure 11

The averaged diffusion coefficient D and corner frequency f_c values of 12 microgels per sample are presented for samples with different amounts of iron oxide nanocubes [19]. The dashed and solid lines represent linear and Gaussian-like fittings, respectively, enabling the calibration of temperature corresponding to each laser power.

Figure 12

(a) Schematic representation of an optically trapped microgel decorated with iron oxide nanocubes, below and above the VPTT. The inset shows the trapped microgel captured with a CMOS camera. (b) Diffusivity D of individual microgels as functions of laser power P. The D plots are vertically offset for clarity, as indicated in the legends. Arrows mark the discontinuous transitions for each microgel [19].