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  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Soft Sci.</journal-id>
      <journal-id journal-id-type="publisher-id">SS</journal-id>
      <journal-title-group>
        <journal-title>Soft Science</journal-title>
      </journal-title-group>
      <issn pub-type="epub">2769-5441</issn>
      <publisher>
        <publisher-name>OAE Publishing Inc.</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="doi">10.20517/ss.2026.67</article-id>
      <article-categories>
        <subj-group>
          <subject>Review Article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Soft yet robust hydrogels for flexible bio-integrated devices: from mechanics properties to applications</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Yang</surname>
            <given-names>Kai</given-names>
          </name>
          <xref ref-type="aff" rid="I1">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="I2">
            <sup>2</sup>
          </xref>
          <xref ref-type="aff" rid="I3">
            <sup>3</sup>
          </xref>
          <xref ref-type="aff" rid="I#">
            <sup>#</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Liu</surname>
            <given-names>Wengang</given-names>
          </name>
          <xref ref-type="aff" rid="I4">
            <sup>4</sup>
          </xref>
          <xref ref-type="aff" rid="I#">
            <sup>#</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Yi</surname>
            <given-names>Zede</given-names>
          </name>
          <xref ref-type="aff" rid="I2">
            <sup>2</sup>
          </xref>
          <xref ref-type="aff" rid="I3">
            <sup>3</sup>
          </xref>
          <xref ref-type="aff" rid="I#">
            <sup>#</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Lu</surname>
            <given-names>Chengbang</given-names>
          </name>
          <xref ref-type="aff" rid="I2">
            <sup>2</sup>
          </xref>
          <xref ref-type="aff" rid="I3">
            <sup>3</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author" corresp="yes">
          <name>
            <surname>Yang</surname>
            <given-names>Xiao</given-names>
          </name>
          <xref ref-type="aff" rid="I5">
            <sup>5</sup>
          </xref>
          <xref ref-type="aff" rid="I*">
            <sup>*</sup>
          </xref>
          <xref ref-type="corresp" rid="cor1" />
        </contrib>
        <contrib contrib-type="author" corresp="yes">
          <name>
            <surname>Zhu</surname>
            <given-names>Weibin</given-names>
          </name>
          <xref ref-type="aff" rid="I4">
            <sup>4</sup>
          </xref>
          <xref ref-type="aff" rid="I*">
            <sup>*</sup>
          </xref>
          <xref ref-type="corresp" rid="cor1" />
        </contrib>
        <contrib contrib-type="author" corresp="yes">
          <name>
            <surname>Liang</surname>
            <given-names>Xiangyu</given-names>
          </name>
          <xref ref-type="aff" rid="I2">
            <sup>2</sup>
          </xref>
          <xref ref-type="aff" rid="I3">
            <sup>3</sup>
          </xref>
          <xref ref-type="aff" rid="I*">
            <sup>*</sup>
          </xref>
          <xref ref-type="corresp" rid="cor1" />
          <contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-3663-8394</contrib-id>
        </contrib>
      </contrib-group>
      <aff id="I1">
        <sup>1</sup>School of Petrochemical Engineering, Changzhou University, Changzhou 213164, Jiangsu, China.</aff>
      <aff id="I2">
        <sup>2</sup>Institute of Bast Fiber Crops &amp; Center of Southern Economic Crops, Chinese Academy of Agricultural Sciences, Changsha 410205, Hunan, China.</aff>
      <aff id="I3">
        <sup>3</sup>Agricultural Genomics Institute at Shenzhen Chinese Academy of Agricultural Sciences, Shenzhen 518000, Guangdong, China.</aff>
      <aff id="I4">
        <sup>4</sup>Hong Kong Centre for Cerebro-cardiovascular Health Engineering, Hong Kong 999077, China.</aff>
      <aff id="I5">
        <sup>5</sup>Department of Mechanical Engineering, The Hong Kong Polytechnic University, Hong Kong 999077, China.</aff>
      <aff id="I#">
        <sup>#</sup>Authors contributed equally to this work.</aff>
      <author-notes>
        <corresp id="cor1"><sup>*</sup>Correspondence to: Prof. Xiangyu Liang, Agricultural Genomics Institute at Shenzhen Chinese Academy of Agricultural Sciences, Shenzhen 518000, Guangdong, China. E-mail: <email>liangxiangyu@caas.cn</email>; Dr. Weibin Zhu, Hong Kong Centre for Cerebro-cardiovascular Health Engineering, Hong Kong 999077, China. E-mail: <email>wbzhu@hkcoche.org</email>; Dr. Xiao Yang, Department of Mechanical Engineering, The Hong Kong Polytechnic University, Hong Kong 999077, China. E-mail: <email>xiaoyang001@cuhk.edu.hk</email></corresp>
        <fn fn-type="other">
          <p>
            <bold>Received:</bold> 4 Apr 2026 | <bold>First Decision:</bold> 9 May 2026 |  <bold>Revised:</bold> 23 May 2026 |  <bold>Accepted:</bold> 10 Jun 2026 |  <bold>Published:</bold> 10 Aug 2026</p>
        </fn>
        <fn fn-type="other">
          <p>
            <bold>Academic Editor:</bold> Huanyu “Larry” Cheng |  <bold>Copy Editor:</bold> Pei-Yun Wang |  <bold>Production Editor:</bold> Pei-Yun Wang</p>
        </fn>
      </author-notes>
      <pub-date pub-type="ppub">
        <year>2026</year>
      </pub-date>
      <pub-date pub-type="epub">
        <day>10</day>
        <month>8</month>
        <year>2026</year>
      </pub-date>
      <volume>6</volume>
	  <issue>3</issue>
      <elocation-id>73</elocation-id>
      <permissions>
        <copyright-statement>© The Author(s) 2026.</copyright-statement>
        <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
          <license-p>© The Author(s) 2026. <bold>Open Access</bold> This article is licensed under a Creative Commons Attribution 4.0 International License (<uri xlink:href="https://creativecommons.org/licenses/by/4.0/">https://creativecommons.org/licenses/by/4.0/</uri>), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.</license-p>
        </license>
      </permissions>
      <abstract>
        <p>Soft hydrogels have emerged as key enabling materials for flexible bio-integrated devices owing to their tissue-like softness, high water content, and intrinsic biocompatibility. However, conventional hydrogels suffer from mechanical fragility, limited fatigue resistance, and poor environmental stability, which severely restrict their long-term performance under dynamic physiological conditions. Addressing this challenge has driven the development of combining compliant mechanics with high toughness, durability, and damage tolerance. This review provides a comprehensive overview of recent advances in robust soft hydrogels for flexible bio-integrated devices, with an emphasis on mechanics-guided design and manufacturing strategies. We first discussed molecular and network-level design principles, including chain architecture, dynamic crosslinking, double network structures, and sacrificial energy dissipation, that underpin enhanced toughness and fatigue resistance. We then examine mesoscale and microstructural engineering approaches, such as gradient architectures, anisotropic networks, and nanocomposite reinforcement, that enable mechanical programmability and environmental robustness. Fabrication and scalability strategies, including printing, patterning, and interface engineering, are subsequently reviewed to highlight pathways toward system-level integration. Finally, emerging applications in flexible electronics, electronic skin, soft robotics, and intelligent health monitoring are discussed, together with remaining challenges and future directions for translating robust soft hydrogels into reliable and manufacturable bio-integrated systems.</p>
      </abstract>
      <kwd-group>
        <kwd>Robust hydrogels</kwd>
        <kwd>flexible bioelectronics</kwd>
        <kwd>mechanical robustness</kwd>
        <kwd>network architecture</kwd>
        <kwd>fabrication strategies</kwd>
        <kwd>interfacial engineering</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec id="sec1">
      <title>INTRODUCTION</title>
      <p>With rapid advances in materials science, electronic technology, and biomedicine, flexible bio-integrated devices have an important platform for bridging living tissues and electronic systems<sup>[<xref ref-type="bibr" rid="B1">1</xref>-<xref ref-type="bibr" rid="B3">3</xref>]</sup>. Confronted with the inherent limitations of traditional rigid electronic devices, which suffer from pronounced mechanical incompatibility with the soft, dynamic nature of biological tissues, flexible integrated devices have distinguished themselves through their excellent performances<sup>[<xref ref-type="bibr" rid="B4">4</xref>-<xref ref-type="bibr" rid="B7">7</xref>]</sup>. These devices not only exhibit exceptional conformability to biological tissues, enabling seamless mechanical and biological integration, but also unlock a plethora of cutting-edge applications, including electronic skin (e-skin)<sup>[<xref ref-type="bibr" rid="B8">8</xref>,<xref ref-type="bibr" rid="B9">9</xref>]</sup>, wearable biosensors<sup>[<xref ref-type="bibr" rid="B10">10</xref>,<xref ref-type="bibr" rid="B11">11</xref>]</sup>, implantable monitoring systems<sup>[<xref ref-type="bibr" rid="B12">12</xref>,<xref ref-type="bibr" rid="B13">13</xref>]</sup>, and soft robotic platforms<sup>[<xref ref-type="bibr" rid="B7">7</xref>]</sup>. The design and development of these devices necessitate materials that not only demonstrate superior biocompatibility to ensure intimate tissue integration but also uphold long-term stability, safety, and functionality<sup>[<xref ref-type="bibr" rid="B14">14</xref>-<xref ref-type="bibr" rid="B16">16</xref>]</sup>. Consequently, the pivotal challenge propelling sustained innovation in the realm of flexible bio-integrated devices lies in achieving an optimal equilibrium between mechanical robustness and biocompatibility. Addressing this challenge is instrumental in advancing the frontiers of this burgeoning field, fostering the realization of next generation bioelectronic interfaces with unprecedented capabilities and performance.</p>
      <p>Hydrogels, composed of hydrophilic three-dimensional polymer networks, have attracted attention as candidate materials for flexible bio-integrated devices<sup>[<xref ref-type="bibr" rid="B17">17</xref>,<xref ref-type="bibr" rid="B18">18</xref>]</sup>. Their soft, water-rich structures closely mimic the extracellular matrix, enabling excellent biocompatibility and tissue-like mechanical properties<sup>[<xref ref-type="bibr" rid="B19">19</xref>,<xref ref-type="bibr" rid="B20">20</xref>]</sup>. This unique matching minimizes foreign body response and fibrotic encapsulation, thereby supporting stable and nearly invisible interfaces with biological systems<sup>[<xref ref-type="bibr" rid="B21">21</xref>,<xref ref-type="bibr" rid="B22">22</xref>]</sup>. Beyond biocompatibility, hydrogels offer optical transparency for optogenetic and imaging applications, as well as intrinsic ionic conductivity that naturally aligns with ion-based electrophysiological signaling in living tissues. These attributes position hydrogels as highly promising flexible bio-integrated platforms for continuous health monitoring<sup>[<xref ref-type="bibr" rid="B23">23</xref>,<xref ref-type="bibr" rid="B24">24</xref>]</sup>, neural stimulation<sup>[<xref ref-type="bibr" rid="B25">25</xref>,<xref ref-type="bibr" rid="B26">26</xref>]</sup>, drug delivery<sup>[<xref ref-type="bibr" rid="B27">27</xref>,<xref ref-type="bibr" rid="B28">28</xref>]</sup>, and even brain-computer interfaces<sup>[<xref ref-type="bibr" rid="B29">29</xref>,<xref ref-type="bibr" rid="B30">30</xref>]</sup>. However, conventional hydrogels remain far from ideal. Their mechanical fragility, reflected in low fracture toughness, poor fatigue resistance, and susceptibility to tearing, limits durability under repeated deformation in dynamic biological environments<sup>[<xref ref-type="bibr" rid="B31">31</xref>]</sup>. At the same time, environmental instability such as uncontrolled swelling, dehydration, and biodegradation undermines their long-term performance <italic>in vivo</italic><sup>[<xref ref-type="bibr" rid="B32">32</xref>,<xref ref-type="bibr" rid="B33">33</xref>]</sup>.These drawbacks highlight the urgent need for soft yet robust hydrogels that combine softness with mechanical resilience, where robustness is defined by high fatigue durability, enhanced fracture toughness, large elongation capacity and extended cycle life under dynamic loading.</p>
      <p>Soft yet robust hydrogels represent a class of polymeric networks that combine high mechanical robustness with tissue-like softness, making them particularly suitable for flexible biomedical electronic applications<sup>[<xref ref-type="bibr" rid="B34">34</xref>-<xref ref-type="bibr" rid="B36">36</xref>]</sup>. Unlike conventional hydrogels that often suffer from brittleness and poor mechanical resilience, strong and tough hydrogels are characterized by their ability to withstand repeated mechanical loading without structural failure. Key indicators of their performance include fatigue durability (the capacity to resist damage under cyclic stress), fracture toughness (the energy required to propagate a crack through the material), elongation at break (the extent to which the hydrogel can stretch before rupture), and cycle life (the number of deformation cycles the hydrogel can endure while maintaining integrity). These parameters collectively determine the hydrogel’s reliability in demanding environments such as load-bearing tissue scaffolds, artificial cartilage, or long-term drug delivery systems<sup>[<xref ref-type="bibr" rid="B37">37</xref>,<xref ref-type="bibr" rid="B38">38</xref>]</sup>.</p>
      <p>The objective of this review is to provide a comprehensive overview of recent advances in soft yet robust hydrogels for flexible bio-integrated devices, as illustrated in <xref ref-type="fig" rid="fig1">Figure 1</xref>. Beginning with multi-scale mechanical design strategies at the molecular, network, and macroscopic levels, we discuss how toughness, fatigue durability, and environmental stability can be enhanced through structural engineering. We then examine fabrication and scalability approaches, including advanced printing, microfabrication, and interface packaging technologies, which enable reliable integration with electronic components and biological tissues. Building on these foundations, we highlight representative applications in wearable electronics, e-skin, soft robotics, and multimodal biosensing systems, emphasizing the role of hydrogels in bridging mechanics, materials engineering, and biomedical functionality. Finally, we look ahead to emerging trends such as artificial intelligence-assisted material design, intelligent interfaces, and sustainable commercialization pathways, aiming to outline how robust hydrogel platforms can evolve into clinically viable and environmentally responsible solutions for next-generation precision medicine and health monitoring.</p>
      <fig id="fig1" position="float" width="570">
        <label>Figure 1</label>
        <caption>
          <p>Overview of recent advances in soft yet robust hydrogels for flexible bio-integrated devices.</p>
        </caption>
        <graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="ss6067.fig.1.jpg" />
      </fig>
    </sec>
    <sec id="sec2">
      <title>MECHANICS OF SOFT YET ROBUST HYDROGELS</title>
      <sec id="sec2-1">
        <title>Molecular/chain-level structure strategy</title>
        <p>Molecular and chain-level structures are the key factors that determine the fundamental properties of hydrogels. By carefully tuning chain flexibility, crosslinking density, branching/side-chain architecture, and self-assembly/noncovalent interactions, the mechanical performance of hydrogels can be precisely designed <InlineParagraph>[<xref ref-type="table" rid="t1">Table 1</xref>].</InlineParagraph></p>
        <table-wrap id="t1">
          <label>Table 1</label>
          <caption>
            <p>Design strategies for mechanically robust hydrogels</p>
          </caption>
          <table frame="hsides" rules="groups">
            <thead>
              <tr>
                <td style="border-bottom:1;">
                  <bold>Strategy</bold>
                </td>
                <td style="border-bottom:1;">
                  <bold>Key mechanism</bold>
                </td>
                <td style="border-bottom:1;">
                  <bold>Typical materials</bold>
                </td>
                <td style="border-bottom:1;">
                  <bold>Mechanical performance</bold>
                </td>
                <td style="border-bottom:1;">
                  <bold>Advantages</bold>
                </td>
                <td style="border-bottom:1;">
                  <bold>Ref.</bold>
                </td>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td>Chain flexibility</td>
                <td>Adjust chain mobility</td>
                <td>Different molecular weight PVA</td>
                <td>High stretchability, reversible large deformation</td>
                <td>Softness, deformability, </td>
                <td>Chen <italic>et al.</italic><sup>[<xref ref-type="bibr" rid="B39">39</xref>]</sup></td>
              </tr>
              <tr>
                <td>Crosslinking density</td>
                <td>Crosslink control</td>
                <td>PAM + N,N′-methylenebisacrylamide</td>
                <td>Enhanced tensile strength, hardness</td>
                <td>Tunable strength and stability</td>
                <td>Kim <italic>et al.</italic><sup>[<xref ref-type="bibr" rid="B40">40</xref>]</sup></td>
              </tr>
              <tr>
                <td>Branching and side-chains</td>
                <td>Entanglement and phase regulation</td>
                <td>Hydrophobic association hydrogels</td>
                <td>High toughness and phase stability</td>
                <td>Functional tunability, improved stability</td>
                <td>Pan <italic>et al.</italic><sup>[<xref ref-type="bibr" rid="B41">41</xref>]</sup></td>
              </tr>
              <tr>
                <td>Noncovalent interactions</td>
                <td>Reversible bonding</td>
                <td>PVA–borate hydrogels</td>
                <td>Self-healing and reversibility</td>
                <td>Dynamic reversibility, damage recovery</td>
                <td>Qian <italic>et al.</italic><sup>[<xref ref-type="bibr" rid="B42">42</xref>]</sup></td>
              </tr>
              <tr>
                <td>Double/multiple networks</td>
                <td>Rigid + flexible synergy</td>
                <td>PAM + alginate DN hydrogels</td>
                <td>High toughness and fatigue resistance</td>
                <td>Superior toughness, load-bearing capacity</td>
                <td>Zhou <italic>et al.</italic><sup>[<xref ref-type="bibr" rid="B43">43</xref>]</sup></td>
              </tr>
              <tr>
                <td>Slide-ring structures</td>
                <td>Stress redistribution</td>
                <td>Slide-ring DN hydrogels</td>
                <td>High stretchability and fatigue resistance</td>
                <td>Stretchability, fatigue resistance</td>
                <td>Wang <italic>et al.</italic><sup>[<xref ref-type="bibr" rid="B44">44</xref>]</sup></td>
              </tr>
              <tr>
                <td>Sacrificial networks</td>
                <td>Energy dissipation</td>
                <td>Enzyme-cleavable peptide bond networks</td>
                <td>High toughness and recoverability</td>
                <td>High toughness, recoverability</td>
                <td>He <italic>et al.</italic><sup>[<xref ref-type="bibr" rid="B45">45</xref>]</sup></td>
              </tr>
              <tr>
                <td>Pore structures</td>
                <td>Pore architecture</td>
                <td>Granular GelMA scaffolds</td>
                <td>High porosity and transport efficiency</td>
                <td>Enhanced transport, tissue integration</td>
                <td>Kedzierski <italic>et al.</italic><sup>[<xref ref-type="bibr" rid="B46">46</xref>]</sup></td>
              </tr>
              <tr>
                <td>Gradient structures</td>
                <td>Modulus gradient</td>
                <td>PEG-based hydrogel composites</td>
                <td>Gradient strength and modulus</td>
                <td>Matches native tissue gradients</td>
                <td>Eckstein <italic>et al.</italic><sup>[<xref ref-type="bibr" rid="B47">47</xref>]</sup></td>
              </tr>
              <tr>
                <td>Layered/aligned fibers</td>
                <td>Fiber orientation</td>
                <td>CNF/MXene, CNT hydrogels</td>
                <td>Anisotropic conductivity and toughness</td>
                <td>Directional strength and conductivity</td>
                <td>Geng <italic>et al.</italic><sup>[<xref ref-type="bibr" rid="B48">48</xref>]</sup></td>
              </tr>
              <tr>
                <td>Nano-reinforcements</td>
                <td>Nano reinforcement</td>
                <td>MgFe-LDH nanosheets + chitosan/silk fibroin</td>
                <td>High reinforcement and responsiveness</td>
                <td>Thermoresponsive, injectable</td>
                <td>Lv <italic>et al.</italic><sup>[<xref ref-type="bibr" rid="B49">49</xref>]</sup></td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn>
              <p>PVA: Poly(vinyl alcohol); PAM: polyacrylamide; DN: double-network; GelMA: gelatin methacryloyl; PEG: polyethylene glycol; CNF: cellulose nanofiber; CNT: carbon nanotube; LDH: layered double hydroxide.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <sec id="sec2-1-1">
          <title>Chain flexibility</title>
          <p>Chain flexibility reflects the ability of polymer segments to rotate and move freely in space<sup>[<xref ref-type="bibr" rid="B50">50</xref>]</sup>. Hydrogels with high chain flexibility allow polymer chains to adjust their conformations more easily<sup>[<xref ref-type="bibr" rid="B51">51</xref>]</sup>, thereby imparting excellent softness and deformability [<xref ref-type="fig" rid="fig2">Figure 2A</xref>]<sup>[<xref ref-type="bibr" rid="B40">40</xref>]</sup>. For example, in poly(vinyl alcohol) (PVA) hydrogels, chain flexibility can be tuned by controlling the molecular weight and degree of polymerization<sup>[<xref ref-type="bibr" rid="B39">39</xref>]</sup>. Wang <italic>et al.</italic> developed a PVA-based hydrogel for epidermal electronics that exhibits high stretchability, mechanical resilience, and stable sensing performance. The flexibility and mobility of PVA chains allow the hydrogel network to dynamically rearrange under external stress, allowing large and reversible deformation. Such behavior is particularly advantageous for flexible sensors subjected to frequent bending and cyclic deformation<sup>[<xref ref-type="bibr" rid="B56">56</xref>]</sup>.</p>
          <fig id="fig2" position="float">
            <label>Figure 2</label>
            <caption>
              <p>Molecular/chain-level structure strategy. (A) Chain flexibility tuned by molecular weight and degree of polymerization<sup>[<xref ref-type="bibr" rid="B40">40</xref>,<xref ref-type="bibr" rid="B52">52</xref>]</sup>. Copyright 2021, The American Association for the Advancement of Science; Copyright 2022, Wiley-VCH; (B) Crosslinking density<sup>[<xref ref-type="bibr" rid="B53">53</xref>]</sup>. Copyright 2023, Wiley-VCH; (C) Branching and side-chain structures<sup>[<xref ref-type="bibr" rid="B41">41</xref>]</sup>. Copyright 2021, American Chemical Society; (D) Self-assembly and noncovalent interactions; (E) Double/multiple network structures. (D and E) are reprinted with permission from Ref.<sup>[<xref ref-type="bibr" rid="B34">34</xref>]</sup>. Copyright 2024, Springer Nature; (F) Slide-ring and fully sliding structures<sup>[<xref ref-type="bibr" rid="B54">54</xref>]</sup>. Copyright 2010, Elsevier; (G) Sacrificial network design<sup>[<xref ref-type="bibr" rid="B55">55</xref>]</sup>. Copyright 2025, Innovation Press. PVA: Poly(vinyl alcohol).</p>
            </caption>
            <graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="ss6067.fig.2.jpg" />
          </fig>
        </sec>
        <sec id="sec2-1-2">
          <title>Crosslinking density</title>
          <p>Crosslinking density refers to the number of crosslinking points per unit volume, which plays a critical role in mechanical strength, swelling behavior, and stability [<xref ref-type="fig" rid="fig2">Figure 2B</xref>]<sup>[<xref ref-type="bibr" rid="B53">53</xref>]</sup>. Increasing crosslinking density generally enhances mechanical strength by restricting chain mobility, making the hydrogel more resistant to stretching or compression<sup>[<xref ref-type="bibr" rid="B53">53</xref>]</sup>. However, excessive crosslinking may lead to brittleness and reduced toughness. For instance, in polyacrylamide (PAM) hydrogels, the amount of crosslinker (e.g., N, N′-methylenebisacrylamide<sup>[<xref ref-type="bibr" rid="B40">40</xref>]</sup>) can be precisely adjusted to control crosslinking density. Moderate increases in crosslinker content significantly improve tensile strength and hardness, but excessive amounts result in fragile hydrogels prone to fracture under stress<sup>[<xref ref-type="bibr" rid="B40">40</xref>]</sup>.</p>
        </sec>
        <sec id="sec2-1-3">
          <title>Branching and side-chain structures</title>
          <p>Introducing branching or side-chain architecture provides an effective strategy to regulate hydrogel mechanics and functionality. Branching increases chain entanglement, thereby enhancing mechanical strength and stability. Side chains, depending on their length, chemical nature, and spatial distribution, can impart specific functionalities<sup>[<xref ref-type="bibr" rid="B57">57</xref>]</sup>. For example, Pan <italic>et al.</italic> proposed a molecular design strategy to regulate phase separation in hydrophobic association hydrogels by tuning short alkyl side-chain length [<xref ref-type="fig" rid="fig2">Figure 2C</xref>]<sup>[<xref ref-type="bibr" rid="B41">41</xref>]</sup>. They found that enhanced hydrophobic interactions increase the size of polymer-rich domains and shift the relaxation dynamics toward higher glass-transition temperatures. Importantly, high strength and toughness are achieved when deformation conditions match the intrinsic relaxation behavior, indicating that phase separation and glass transition jointly govern mechanical performance<sup>[<xref ref-type="bibr" rid="B41">41</xref>]</sup>.</p>
        </sec>
        <sec id="sec2-1-4">
          <title>Self-assembly and noncovalent interactions</title>
          <p>Self-assembly and noncovalent interactions (e.g., hydrogen bonding<sup>[<xref ref-type="bibr" rid="B58">58</xref>]</sup>, van der Waals forces<sup>[<xref ref-type="bibr" rid="B59">59</xref>]</sup>, π-π stacking<sup>[<xref ref-type="bibr" rid="B60">60</xref>]</sup>) play vital roles in hydrogel structure formation and property regulation [<xref ref-type="fig" rid="fig2">Figure 2D</xref>]<sup>[<xref ref-type="bibr" rid="B34">34</xref>]</sup>. These interactions are dynamic and reversible, enabling hydrogels to undergo reversible deformation and exhibit self-healing capability. For instance, hydrogen-bonded hydrogels can reform broken bonds after damage, restoring integrity. A typical example is PVA-borate hydrogels<sup>[<xref ref-type="bibr" rid="B42">42</xref>]</sup>, where hydroxyl groups on PVA chains interact with borate ions to form a three-dimensional network. Upon cutting or stretching, the damaged regions can self-repair through reformation of hydrogen bonds, recovering mechanical performance.</p>
        </sec>
        <sec id="sec2-1-5">
          <title>Double/multiple network structures</title>
          <p>Double or multiple network hydrogels consist of two or more interpenetrating or interwoven networks, endowing them with superior mechanical strength and multifunctionality [<xref ref-type="fig" rid="fig2">Figure 2E</xref>]<sup>[<xref ref-type="bibr" rid="B61">61</xref>]</sup>. Networks can be interconnected via chemical crosslinking or physical interactions, working synergistically to enhance toughness<sup>[<xref ref-type="bibr" rid="B62">62</xref>,<xref ref-type="bibr" rid="B63">63</xref>]</sup>. A typical double-network hydrogel combines a rigid network with a flexible one: the rigid network provides strength and resistance to stretching, while the flexible network dissipates energy and prevents catastrophic fracture<sup>[<xref ref-type="bibr" rid="B43">43</xref>]</sup>. This architecture yields hydrogels with high strength, flexibility, and fatigue resistance, suitable for load-bearing and wear-resistant applications.</p>
        </sec>
        <sec id="sec2-1-6">
          <title>Slide-ring and fully sliding structures</title>
          <p>Slide-ring networks represent an advanced topological design in hydrogel mechanics [<xref ref-type="fig" rid="fig2">Figure 2F</xref>]<sup>[<xref ref-type="bibr" rid="B54">54</xref>]</sup>. By introducing movable ring molecules onto polymer chains, stress can be effectively redistributed during deformation<sup>[<xref ref-type="bibr" rid="B64">64</xref>]</sup>. The sliding motion of rings enhances stretchability and toughness. Fully sliding structures extend this concept, allowing all network junctions to move freely, resulting in extraordinary flexibility and extensibility<sup>[<xref ref-type="bibr" rid="B54">54</xref>]</sup>. Wang <italic>et al.</italic> introduced slide-ring crosslinking points into a double-network (DN) hydrogel and showed that chain sliding at these movable junctions significantly enhances mechanical adaptability<sup>[<xref ref-type="bibr" rid="B44">44</xref>]</sup>. The hydrogel achieved reversible tensile deformation above 300%, an elastic modulus of approximately 300-500 kPa and maintained stable sensing signals after over 10,000 cyclic deformations. These results confirm that slide-ring dynamics play a critical role in mitigating stress concentration and improving fatigue resistance in flexible hydrogel systems.</p>
        </sec>
        <sec id="sec2-1-7">
          <title>Sacrificial network design</title>
          <p>Sacrificial networks are incorporated to improve toughness and fatigue resistance [<xref ref-type="fig" rid="fig2">Figure 2G</xref>]<sup>[<xref ref-type="bibr" rid="B55">55</xref>]</sup>. These networks, with relatively low mechanical strength, preferentially fracture under stress, dissipating energy and protecting the primary network<sup>[<xref ref-type="bibr" rid="B65">65</xref>]</sup>. By rationally designing the structure and properties of sacrificial networks, hydrogel mechanics can be finely tuned to meet diverse application requirements<sup>[<xref ref-type="bibr" rid="B66">66</xref>]</sup>. He <italic>et al.</italic> proposed a DN hydrogel in which the densely crosslinked sacrificial network is built from enzyme-cleavable covalent peptide bonds<sup>[<xref ref-type="bibr" rid="B45">45</xref>]</sup>. They demonstrated that, under force-coupled enzymatic catalysis, the sacrificial network can undergo reversible rupture and reformation, enabling recoverable energy dissipation rather than permanent damage. As a result, the hydrogel combines high toughness and reversibility<sup>[<xref ref-type="bibr" rid="B45">45</xref>]</sup>, exhibiting fracture strains above 2,000%, a maximum toughness of 15 MJ·m<sup>-3</sup>, and a fracture energy of 9.4 kJ·m<sup>-2</sup>, while allowing mechanical recovery and self-healing after cyclic loading.</p>
        </sec>
      </sec>
      <sec id="sec2-2">
        <title>Network and microstructure regulation</title>
        <p>Beyond molecular and chain-level structures, the network architecture and microstructural features of hydrogels also play crucial roles in determining their mechanical and functional properties. By tailoring pore structures, constructing gradient architectures, designing layered or aligned fiber structures, and incorporating nanofillers or nano-reinforcements, hydrogel performance can be further optimized.</p>
        <sec id="sec2-2-1">
          <title>Pore structures</title>
          <p>Pore structures are fundamental characteristics of hydrogels, encompassing pore size, distribution, and connectivity<sup>[<xref ref-type="bibr" rid="B67">67</xref>]</sup>. They significantly influence stress-strain transmission and fatigue life. Larger pores facilitate transport and diffusion, enhancing swelling kinetics and drug release efficiency. However, excessively large pores may weaken mechanical strength due to thin pore walls that cannot withstand high stress. Uniform pore size distribution helps distribute stress evenly, reducing local stress concentration and improving fatigue resistance. High pore connectivity facilitates rapid mass transport throughout the hydrogel, enhancing functionality<sup>[<xref ref-type="bibr" rid="B68">68</xref>]</sup>. For example, in tissue engineering scaffolds, controlling pore architecture enables hydrogels to mimic the extracellular matrix by providing cell-scale void spaces and efficient nutrient transport pathways. Granular gelatin methacryloyl (GelMA) hydrogel scaffolds constructed from porous microgels exhibit hierarchical inter- and intraparticle porosity, delivering up to 170% higher void fraction and 57%-78% increase <italic>in vivo</italic> cell infiltration compared with nonporous counterparts, thereby effectively promoting cell adhesion, migration, and tissue integration. Importantly, quantitative mechanical analyses have shown that increasing pore size from ~8 to ~24 μm can redistribute stress and enhance fracture energy by approximately 2.5-fold, while simultaneously delaying fatigue crack propagation<sup>[<xref ref-type="bibr" rid="B46">46</xref>]</sup>. Furthermore, the polyvinyl alcohol hydrogel prepared by the freeze casting process forms a honeycomb-like porous structure [<xref ref-type="fig" rid="fig3">Figure 3A</xref> and <xref ref-type="fig" rid="fig3">B</xref>]<sup>[<xref ref-type="bibr" rid="B69">69</xref>]</sup>. After further annealing, the crystallinity of PVA hydrogels increases by ~15%-20%, which correlates with a ~2× improvement in compressive modulus and enhanced toughness. This evidence underscores the quantitative role of pore size and connectivity in enhancing fracture toughness and fatigue resistance of hydrogel networks<sup>[<xref ref-type="bibr" rid="B69">69</xref>]</sup>.</p>
          <fig id="fig3" position="float" width="560">
            <label>Figure 3</label>
            <caption>
              <p>Design of hydrogel networks and microstructures. (A) Schematic illustration for the hydrogel fabrication by freezing a polymer solution on a copper substrate; (B) SEM images of the freeze-casted and annealed (FC-A) PVA hydrogels. (A and B) are reprinted with permission from Ref.<sup>[<xref ref-type="bibr" rid="B69">69</xref>]</sup>. Copyright 2021, Wiley-VCH; (C) Fabrication process: (i) 3D Printing, (ii) Mechanical Training, (iii) Electrochemical Training<sup>[<xref ref-type="bibr" rid="B74">74</xref>]</sup>. Copyright 2026, Wiley-VCH; (D) Preparation of biomimetic chitin-protein <italic>OfCPH-2</italic> (BM)-hydrogel<sup>[<xref ref-type="bibr" rid="B76">76</xref>]</sup>. Copyright 2025, Wiley-VCH; (E) Schematic illustration of the fabrication of CSP-LB hydrogel<sup>[<xref ref-type="bibr" rid="B49">49</xref>]</sup>. Copyright 2023, Wiley-VCH. SEM: Scanning electron microscopy; PVA: poly(vinyl alcohol); BM: biomimetic chitin-protein O<italic>f</italic>CPH-2; CSP-LB: chitosan/silk fibroin (CS) hydrogels loaded with platelet-derived growth factor-BB (PDGF-BB) to construct a smart injectable thermo-responsive hydroge; HFIP: hexafluoroisopropanol; LDHs: layered double hydroxides; BMP-2: bone morphogenetic protein 2; PDGF-BB: platelet-derived growth factor-BB.</p>
            </caption>
            <graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="ss6067.fig.3.jpg" />
          </fig>
        </sec>
        <sec id="sec2-2-2">
          <title>Gradient structures</title>
          <p>Gradient structures are widely used to reconcile mechanical mismatches across biological interfaces<sup>[<xref ref-type="bibr" rid="B70">70</xref>]</sup>. Gradient structures refer to spatial variations in physical or chemical properties within hydrogels. Such architectures enable different regions to exhibit distinct performances, meeting complex application requirements, and more importantly, they redistribute stresses under cyclic loading. By gradually varying stiffness across the interface, superficial regions experience moderated strain amplitudes while deeper regions sustain lower strain levels (&lt; 10%), thereby alleviating stress concentration, homogenizing load transfer, and delaying fatigue crack initiation during repeated deformation cycles<sup>[<xref ref-type="bibr" rid="B71">71</xref>]</sup>. For joint repair, hydrogels can be engineered with gradient mechanical properties so that the cartilage-side region presents a lower elastic modulus matching native cartilage (1 MPa) and mitigating local stress, while the bone-side region is substantially stiffer (5.8-6.4 MPa) to provide load-bearing support and interfacial stability<sup>[<xref ref-type="bibr" rid="B72">72</xref>,<xref ref-type="bibr" rid="B73">73</xref>]</sup>. Eckstein <italic>et al.</italic> used digital light projection/microstereolithography-printed polyethylene glycol (PEG)-based hydrogel-composite micro-truss scaffolds with sub-200 μm features and high porosity (68%-81%), the study achieved a controlled cartilage-zone gradient of 0.76-1 MPa and a 6× modulus jump into the bone layer<sup>[<xref ref-type="bibr" rid="B47">47</xref>]</sup>. Importantly, finite element analysis revealed that such gradients redistribute cyclic stresses: superficial regions experienced &gt; 30% strain under compression, while deeper regions maintained &lt; 10% strain, thereby reducing stress concentration and delaying fatigue crack initiation<sup>[<xref ref-type="bibr" rid="B47">47</xref>]</sup>. In addition, Yao <italic>et al.</italic> reported a preparation method termed as electrochemical training that utilizes gradient ionic coordination and molecular locking to achieve rapid assembly of disordered hydrogels [<xref ref-type="fig" rid="fig3">Figure 3C</xref>]<sup>[<xref ref-type="bibr" rid="B74">74</xref>]</sup>. These hydrogels exhibit multiscale anisotropic gradient structures ranging from 5 nm to 2 cm, which not only provide spatially tuned mechanical cues but also homogenize stress transfer under repeated loading, enhancing long-term fatigue resistance.</p>
        </sec>
        <sec id="sec2-2-3">
          <title>Layered or aligned fiber structures</title>
          <p>Layered or aligned fiber architectures introduce anisotropic mechanical, electrical, or transport properties into hydrogel systems. By controlling fiber orientation and hierarchical arrangement, hydrogels can achieve directional mechanical strength, conductivity, or optical performance<sup>[<xref ref-type="bibr" rid="B75">75</xref>]</sup>. For example, inspired by the layered structure of the head capsule of the Asian corn borer, a chitin hydrogel with a layered structure was developed that exhibits excellent impact resistance<sup>[<xref ref-type="bibr" rid="B76">76</xref>]</sup> [<xref ref-type="fig" rid="fig3">Figure 3D</xref>]. Conductive hydrogels can indeed be engineered by aligning conductive micro/nanofibers [e.g., cellulose nanofiber (CNF)/MXene, carbon nanotubes (CNTs)] into an ordered fiber network, which produces direction-dependent electrical pathways<sup>[<xref ref-type="bibr" rid="B76">76</xref>]</sup>. Representative systems show that the conductivity parallel to the fiber alignment markedly exceeds the perpendicular direction: for example, an anisotropic CNF/MXene DN hydrogel reaches <InlineParagraph>13.08 S·m<sup>-1</sup></InlineParagraph> along the alignment and is explicitly used to build direction-selective strain/pressure sensors (the orthogonal direction is significantly less conductive), demonstrating how orientation programs the circuit behavior. Likewise, mechanically stretched, fiber-oriented hydrogels exhibit higher conductivity along the stretch/alignment axis than transverse to it (while simultaneously increasing strength and toughness), further confirming that anisotropy arises from ordered conductive domains<sup>[<xref ref-type="bibr" rid="B48">48</xref>]</sup>.</p>
        </sec>
        <sec id="sec2-2-4">
          <title>Nanofillers and nano-reinforcements</title>
          <p>Incorporating nanofillers or nano-reinforcements provides an effective route to enhance hydrogel mechanical and functional performance. Nanomaterials possess unique physical and chemical properties, such as high surface area, superior mechanical strength, and distinctive optical or electrical characteristics<sup>[<xref ref-type="bibr" rid="B77">77</xref>]</sup>. Uniform dispersion of nanomaterials (e.g., CNTs<sup>[<xref ref-type="bibr" rid="B78">78</xref>]</sup>, nanofibers<sup>[<xref ref-type="bibr" rid="B79">79</xref>]</sup>, nanosheets<sup>[<xref ref-type="bibr" rid="B49">49</xref>]</sup>) within hydrogel matrices can significantly improve mechanical strength, conductivity, thermal stability, and bioactivity. Lv <italic>et al.</italic> proposed incorporating MgFe-layered double hydroxide (LDH) nanosheets into a chitosan/silk fibroin hydrogel to reinforce the polymer network and tune its gelation and mechanical properties [<xref ref-type="fig" rid="fig3">Figure 3E</xref>]<sup>[<xref ref-type="bibr" rid="B49">49</xref>]</sup>. They showed that the nanosheets act as physical crosslinking and load-bearing units, significantly shortening gelation time (from 300 to 146 s), lowering the sol-gel transition temperature (37.4 to 32.7 °C), and enhancing the storage and compressive moduli by 12-fold and 10-fold at optimal LDH content (0.1 wt%). Based on these nanosheet-reinforced mechanical properties, the hydrogel was further demonstrated as an injectable thermos-responsive platform for effective bone regeneration.</p>
        </sec>
      </sec>
      <sec id="sec2-3">
        <title>Fatigue performance and environmental stability</title>
        <p>In emerging applications such as flexible electronics, soft actuators, biomimetic materials, and wearable devices, the fatigue performance and environmental stability of materials are critical determinants of long-term service reliability. Soft materials are frequently exposed to complex environmental conditions, including variations in humidity, temperature, and ionic strength, while simultaneously undergoing repeated mechanical deformation such as stretching, compression, or bending. Under these conditions, cyclic loading behavior, moisture exchange, and structural relaxation processes collectively determine the functional lifespan and structural integrity of hydrogel systems. This section reviews recent advances in three key aspects: (i) fatigue behavior under cyclic loading across different humidity, temperature, and salt environments; (ii) performance degradation induced by moisture loss, evaporation, and dry-wet cycling; and (iii) long-term reliability in maintaining deformation recovery and mechanical strength.</p>
        <sec id="sec2-3-1">
          <title>Fatigue behavior under cyclic loading</title>
          <p>Materials used in practical applications are frequently subjected to repeated mechanical deformation, making resistance to mechanical fatigue a key design criterion<sup>[<xref ref-type="bibr" rid="B69">69</xref>]</sup>. Environmental conditions have been widely shown to exert a strong influence on material performance during cyclic loading. In high humidity environments, water molecules can penetrate polymer networks and act as plasticizers, reducing modulus while enhancing chain mobility<sup>[<xref ref-type="bibr" rid="B80">80</xref>]</sup>. Although this effect may temporarily improve flexibility, prolonged exposure often disrupts crosslinking structures and accelerates crack propagation. For example, hydrogels typically exhibit good stretch recovery behavior under humid conditions but may suffer from localized dehydration and pore collapse during prolonged compressive cycling, resulting in increased energy dissipation and accumulation of residual strain<sup>[<xref ref-type="bibr" rid="B81">81</xref>]</sup>.</p>
          <p>Elevated temperatures intensify thermal motion within polymer networks, potentially leading to chain disentanglement, crosslink cleavage, or phase separation, thereby reducing fatigue life<sup>[<xref ref-type="bibr" rid="B82">82</xref>]</sup>. In contrast, low temperatures can embrittle soft materials by suppressing energy dissipation mechanisms, increasing susceptibility to brittle fracture<sup>[<xref ref-type="bibr" rid="B83">83</xref>]</sup>. High salt environments can also significantly influence hydrogel mechanics by screening electrostatic interactions or modifying ionic crosslinking within polymer networks<sup>[<xref ref-type="bibr" rid="B84">84</xref>]</sup>. However, such salt-induced stiffening is often accompanied by reduced elasticity and flexibility of the hydrogel network.</p>
        </sec>
        <sec id="sec2-3-2">
          <title>Fatigue-resistant mechanism</title>
          <p>The core of material fatigue-resistant design is to construct a hierarchical protection system integrating crack suppression, energy dissipation and damage self-repair<sup>[<xref ref-type="bibr" rid="B85">85</xref>,<xref ref-type="bibr" rid="B86">86</xref>]</sup>. While all fatigue-resistant designs aim to restrain crack expansion and reduce cumulative cyclic damage, three mainstream design strategies differ substantially in structural design principles, working mechanisms and fatigue-resistant performances, as summarized in <xref ref-type="table" rid="t2">Table 2</xref>.</p>
          <table-wrap id="t2">
            <label>Table 2</label>
            <caption>
              <p>Comparison of typical fatigue-resistant design strategies for functional soft materials</p>
            </caption>
            <table frame="hsides" rules="groups">
              <thead>
                <tr>
                  <td style="border-bottom:1;">
                    <bold>Design strategy</bold>
                  </td>
                  <td style="border-bottom:1;">
                    <bold>Core design principle</bold>
                  </td>
                  <td style="border-bottom:1;">
                    <bold>Main fatigue-resistant mechanism</bold>
                  </td>
                  <td style="border-bottom:1;">
                    <bold>Key performance characteristics</bold>
                  </td>
                  <td style="border-bottom:1;">
                    <bold>Limitations</bold>
                  </td>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td>Crystalline domain regulation<sup>[<xref ref-type="bibr" rid="B87">87</xref>]</sup></td>
                  <td>Optimize grain size, distribution, and crystallinity; exert synergistic effect of crystalline and amorphous regions</td>
                  <td>Block crack propagation, dissipate strain energy, relieve stress concentration</td>
                  <td>High initial modulus and strength; relatively low fatigue threshold; fast crack propagation rate under large strain</td>
                  <td>Poor ductility, unsuitable for high-strain long-cycle fatigue service</td>
                </tr>
                <tr>
                  <td>Soft network topology modulation<sup>[<xref ref-type="bibr" rid="B89">89</xref>]</sup></td>
                  <td>Construct interpenetrating, sliding, dynamic reversible and high-functional cross-linked networks</td>
                  <td>Realize hierarchical energy dissipation, uniform stress distribution and microdamage self-repair</td>
                  <td>Excellent large deformation adaptability, slow crack growth rate, superior long-cycle fatigue stability</td>
                  <td>Weak high-temperature resistance, easy mechanical attenuation under extreme external load</td>
                </tr>
                <tr>
                  <td>Multiphase composite reinforcement<sup>[<xref ref-type="bibr" rid="B90">90</xref>]</sup></td>
                  <td>Build stable filler-matrix interface, optimize interfacial bonding and gradient structure</td>
                  <td>Reinforcing phase bridging effect, efficient interfacial load transfer, interfacial energy dissipation</td>
                  <td>Adjustable fatigue performance, improved environmental adaptability, balanced mechanical properties</td>
                  <td>Prone to interfacial debonding; complex preparation process, difficult precise regulation</td>
                </tr>
              </tbody>
            </table>
          </table-wrap>
          <p>Crystalline domain modulation represents a typical fatigue improvement strategy applicable to crystalline substances and crystalline polymer composites<sup>[<xref ref-type="bibr" rid="B86">86</xref>]</sup>. Its core design principle focuses on precise regulation of grain size, spatial distribution, and overall crystallinity, and exploits the synergistic interaction between crystalline and amorphous phases to optimize internal stress distribution. This structural optimization strengthens intrinsic crack resistance, realizes efficient strain energy dissipation, and relieves local stress concentration. For instance, in high-molecular-weight PVA hydrogels, cracks grow through the combination of chain sliding and chain breakage. The crystalline domains reduce stress near the crack tip, and the threshold increases with the increase in crystallinity<sup>[<xref ref-type="bibr" rid="B87">87</xref>]</sup>. At 18.9 wt% crystallinity, the threshold can exceed 1,000 J/m<sup>2</sup>. It should be noted that brittleness dominates and fatigue resistance deteriorates beyond ~70% crystallinity<sup>[<xref ref-type="bibr" rid="B87">87</xref>]</sup>. Such rigid structural regulation is limited by low ductility, which usually results in relatively low fatigue threshold and rapid crack propagation rate under large cyclic deformation, restricting its application in high-strain fatigue scenarios.</p>
          <p>In sharp contrast, internal network topology engineering is the dominant design route for flexible soft materials to achieve excellent fatigue resistance<sup>[<xref ref-type="bibr" rid="B88">88</xref>]</sup>. Distinct from rigid crystalline reinforcement, this strategy relies on customized network architectures including interpenetrating networks, sliding crosslinking networks, dynamically reversible crosslinked networks, and high-functionality crosslinked networks. Its unique design logic lies in realizing multi-stage energy dissipation, homogeneous stress redistribution and spontaneous microdamage rehabilitation through flexible chain motion and reversible bond dynamics. For example, a double-network elastomer can achieve fatigue thresholds as high as 500 J/m<sup>2</sup><sup>[<xref ref-type="bibr" rid="B89">89</xref>]</sup>, but at the cost of substantially lower initial modulus (often &lt; 1 MPa <italic>vs.</italic> &gt; 10 MPa for crystalline materials). Furthermore, dynamic reversible cross-links further enable micro-damage self-repair under cyclic loading, a capability absent in purely crystalline designs. Benefiting from such flexible structural characteristics, network-regulated soft materials possess outstanding long-cycle fatigue tolerance and slow crack propagation speed, yet their fatigue stability is easily deteriorated under high-temperature and high-load service conditions.</p>
          <p>Different from the above two strategies, the fatigue-resistant performance of multi-phase composite materials is dominated by reinforcing phase bridging behavior and interfacial load transfer efficiency<sup>[<xref ref-type="bibr" rid="B90">90</xref>]</sup>. Its design philosophy centers on constructing stable filler-matrix interfacial interaction: reinforcing phases across crack gaps generate crack closure force and consume interfacial fracture energy to slow down crack growth. Further interfacial modification strategies including bonding strength optimization, gradient interfacial construction and high-energy phase introduction can effectively block crack extension paths and elevate the critical fatigue threshold of composites. In the optimized system, the fatigue threshold has exceeded 1,000 J/m<sup>2[91]</sup>. However, unreasonable interfacial matching easily causes interfacial debonding failure, which becomes the main factor restricting the further promotion of comprehensive fatigue performance.</p>
          <p>In summary, the three strategies show obvious differences in key fatigue-related quantitative indicators: crystalline regulation achieves high static mechanical strength but poor cyclic fatigue durability; network topology design balances large deformation adaptability and long-cycle stability; composite reinforcement realizes performance complementarity at the expense of increased structural complexity. Recently, emerging advanced material systems integrate the merits of the above design concepts to obtain optimized fatigue resistance under complex service environments, such as dual-network hydrogels, nanofilled elastomers and bionic layered structural materials. Specifically, bidirectional freeze-casting induced layered microstructure provides a feasible route to fabricate isotropic fatigue-resistant materials<sup>[<xref ref-type="bibr" rid="B76">76</xref>,<xref ref-type="bibr" rid="B92">92</xref>,<xref ref-type="bibr" rid="B93">93</xref>]</sup>. Hydrogels with ordered 2D layered structures and finely tuned nanocrystalline domains achieve greatly improved comprehensive mechanical properties<sup>[<xref ref-type="bibr" rid="B94">94</xref>]</sup>. The introduction of rigid nanofillers such as cellulose nanocrystals and MXene can further suppress crack initiation and propagation, endowing materials with reliable fatigue-resistant capability in humid service environments [<xref ref-type="fig" rid="fig4">Figure 4A</xref>]<sup>[<xref ref-type="bibr" rid="B95">95</xref>,<xref ref-type="bibr" rid="B96">96</xref>]</sup>. Moreover, gradient crosslinking design optimizes internal stress field distribution and alleviates local stress accumulation, which is an effective auxiliary means to further enhance the cyclic structural resilience of fatigue-resistant materials.</p>
          <fig id="fig4" position="float">
            <label>Figure 4</label>
            <caption>
              <p>Fatigue performance and environmental stability of hydrogels. (A) Photos of the stretched hydrogel with a notch and tensile stress-strain curves<sup>[<xref ref-type="bibr" rid="B96">96</xref>]</sup>. Copyright 2025, Elsevier; (B) Schematic illustration on the synthesis and structure of PVA/PAM/Zn/EG (PPZE) hydrogel<sup>[<xref ref-type="bibr" rid="B98">98</xref>]</sup>. Copyright 2022, The American Association for the Advancement of Science; (C) Self-healing mechanism of β-cyclodextrin/hyaluronic acid (ACD) hydrogel<sup>[<xref ref-type="bibr" rid="B104">104</xref>]</sup>. Copyright 2025, Elsevier; (D) Self-healing mechanism diagram of PACCMZ hydrogel. Self-healing mechanism<sup>[<xref ref-type="bibr" rid="B103">103</xref>]</sup>. Copyright 2025, Elsevier; (E) Schematic diagram for the preparation of negatively-charged double bond-functionalized polyacrylic acid and positively-charged polyethyleneimine powder (PAA-db/PEI powder)<sup>[<xref ref-type="bibr" rid="B112">112</xref>]</sup>. Copyright 2025, Wiley-VCH; (F) The mechanisms of the shape memory hydrogels with simultaneously switchable fluorescence<sup>[<xref ref-type="bibr" rid="B113">113</xref>]</sup>; Copyright 2018, Wiley-VCH. PVA: Poly(vinyl alcohol); PAM: polyacrylamide; EG: ethylene glycol; PACCMZ: polyacrylamide/carbon nanotube@cellulose/MXene/Zn<sup>2+</sup>; AM: acrylamide; AHA: aldehyde-modified hyaluronic acid; DTP: 3,3′-dithiobis (propionyl hydrazide); CNT: carbon nanotube; CNF: cellulose nanofiber; PAA: polyacrylic acid; PEI: polyethyleneimine.</p>
            </caption>
            <graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="ss6067.fig.4.jpg" />
          </fig>
        </sec>
        <sec id="sec2-3-3">
          <title>Moisture-induced performance degradation</title>
          <p>Moisture exchange is a central factor governing the environmental stability of soft materials, particularly hydrophilic systems such as hydrogels and hygroscopic polymers. Repeated drying and wetting cycles often induce irreversible structural damage. Under low humidity conditions, water evaporation leads to volumetric shrinkage, pore collapse, and network densification, resulting in increased Young modulus at the expense of ductility<sup>[<xref ref-type="bibr" rid="B97">97</xref>]</sup>. This drying-induced contraction is commonly accompanied by interfacial delamination and surface cracking, severely limiting material reusability.</p>
          <p>More critically, repeated dry-wet cycling causes cumulative structural degradation. Although rehydration may partially restore volume, incomplete network reconstruction frequently leads to anisotropic swelling, microcrack propagation, and blockage of ion transport pathways. Rapid evaporation can further generate capillary forces that induce macroscopic wrinkling and delamination, undermining structural integrity. Strategies such as incorporating alcohol have been reported to improve water retention in hydrogels [<xref ref-type="fig" rid="fig4">Figure 4B</xref>]<sup>[<xref ref-type="bibr" rid="B98">98</xref>]</sup>. Nevertheless, complete prevention of water loss remains challenging.</p>
          <p>To address these issues, several approaches have been proposed, including construction of amphiphilic networks using block copolymers or organic inorganic hybrids to regulate water diffusion kinetics<sup>[<xref ref-type="bibr" rid="B99">99</xref>,<xref ref-type="bibr" rid="B100">100</xref>]</sup>, integration of self-healing functionalities through dynamic covalent bonds (e.g., imine or boronate ester linkages) or noncovalent interactions such as hydrogen bonding and metal coordination. to enable post damage repair [<xref ref-type="fig" rid="fig4">Figure 4C</xref> and <xref ref-type="fig" rid="fig4">D</xref>]<sup>[<xref ref-type="bibr" rid="B101">101</xref>-<xref ref-type="bibr" rid="B104">104</xref>]</sup>, and application of encapsulation strategies such as polydimethylsiloxane (PDMS) coatings or microencapsulation to physically shield active layers from environmental exposure<sup>[<xref ref-type="bibr" rid="B105">105</xref>,<xref ref-type="bibr" rid="B106">106</xref>]</sup>.</p>
        </sec>
        <sec id="sec2-3-4">
          <title>Long-term mechanical reliability</title>
          <p>Beyond short term cyclic loading, materials deployed in practical systems must maintain mechanical performance under prolonged static or quasi-static deformation. Most polymer materials, however, exhibit creep and stress relaxation<sup>[<xref ref-type="bibr" rid="B107">107</xref>]</sup>, manifested as progressive deformation under constant load or gradual decay of stress over time, posing challenges for applications requiring dimensional stability or long-term sealing.</p>
          <p>Environmental factors further exacerbate these phenomena. Elevated temperatures accelerate molecular chain slippage and enhance stress relaxation rates<sup>[<xref ref-type="bibr" rid="B108">108</xref>]</sup>, while humidity fluctuations alter free volume and dielectric properties, disrupting internal energy dissipation mechanisms<sup>[<xref ref-type="bibr" rid="B109">109</xref>]</sup>. To improve long term reliability, modern material design increasingly emphasizes multiscale stable network architecture. Crystallizable elastomers, for example, employ reversible crystalline domains as physical crosslinks to preserve modulus even at elevated temperatures<sup>[<xref ref-type="bibr" rid="B110">110</xref>]</sup>. Shape memory polymers provide the ability to recover original shape upon external stimulation, extending effective service life<sup>[<xref ref-type="bibr" rid="B111">111</xref>]</sup>. In addition, environmentally responsive crosslinking modulation, such as photo triggered or pH sensitive networks, enables mechanical reinforcement and opens new opportunities for adaptive material systems [<xref ref-type="fig" rid="fig4">Figure 4E</xref> and <xref ref-type="fig" rid="fig4">F</xref>]<sup>[<xref ref-type="bibr" rid="B112">112</xref>,<xref ref-type="bibr" rid="B113">113</xref>]</sup>.</p>
        </sec>
      </sec>
      <sec id="sec2-4">
        <title>Conductive mechanisms and electrical design of soft hydrogels</title>
        <p>Conductive hydrogels have attracted considerable attention due to their ability to transport ions or electrons, making them a rapidly emerging focus in materials science and biomedical research. Based on their conduction mechanisms, conductive hydrogels can be categorized into three types: ionic conductive hydrogels, electronically conductive hydrogels, and hybrid conductive hydrogels. This section provides a comprehensive overview of their conductive behaviors, with emphasis on the underlying mechanisms, key influencing factors, and potential applications. The discussion aims to offer theoretical insights and practical guidance for the design and utilization of conductive hydrogels in diverse fields.</p>
        <p>The conductive strategies outlined in the previous section effectively overcome the challenge of electrical signal transmission, thereby establishing a foundation for developing “electronic-biological” interfaces. However, for devices to progress beyond functioning as passive signal conduits and advance into intelligent systems that actively adapt to dynamic physiological environments while performing specific functions, it is crucial to endow materials with controllable, multimodal responsiveness to environmental stimuli<sup>[<xref ref-type="bibr" rid="B114">114</xref>-<xref ref-type="bibr" rid="B118">118</xref>]</sup>. Hydrogels exhibiting such responsiveness can transduce external physical or chemical stimuli (such as temperature, pH, light, electricity, magnetism, or specific biomolecules) into observable and functional output signals, including changes in volume, shape, color, or optoelectronic properties, thus enabling real-time feedback on physiological states and intelligent simulation of environmental interactions<sup>[<xref ref-type="bibr" rid="B119">119</xref>-<xref ref-type="bibr" rid="B121">121</xref>]</sup>. Among these responses, volume change represents the most fundamental form, which can be strategically guided toward complex deformations through spatial structural design<sup>[<xref ref-type="bibr" rid="B122">122</xref>,<xref ref-type="bibr" rid="B123">123</xref>]</sup>. Furthermore, coupling periodic structures with volume variations facilitates visualized color feedback, while the integration of light-harvesting moieties with charge transport networks unlocks pathways for efficient optoelectronic conversion. This section systematically elaborates on how hydrogels, via multiscale design, integrate diverse responsive mechanisms and sensing functions to achieve a transition from simple conduction to complex behaviors in flexible bio-integrated devices.</p>
        <sec id="sec2-4-1">
          <title>Ionic conductive hydrogels</title>
          <p>Ionic conductive hydrogels conduct electricity through the directional migration of mobile ions within their hydrated polymer networks. Owing to their high water content, ions such as H<sup>+</sup>, OH<sup>-</sup>, Na<sup>+</sup>, and Cl<sup>-</sup> are readily generated by water dissociation or polymer ionization<sup>[<xref ref-type="bibr" rid="B124">124</xref>]</sup>. Under an external electric field, these ions migrate along concentration or potential gradients, producing ionic current. For example, in sodium polyacrylate-based hydrogels, partial dissociation of sodium carboxylate groups releases Na<sup>+</sup>, and carboxylate counterions, which act as charge carriers within the three-dimensional network<sup>[<xref ref-type="bibr" rid="B125">125</xref>]</sup>. Ionic conductivity is primarily governed by ion concentration, network architecture, and temperature. Higher ion density increases the number of charge carriers, while a loose and porous network provides low-resistance pathways for ion diffusion. Elevated temperature enhances ionic mobility by accelerating segmental motion and diffusion, although excessive heating may destabilize the hydrated structure and compromise conductivity<sup>[<xref ref-type="bibr" rid="B126">126</xref>]</sup>. Importantly, because ionic transport depends on hydrated channels, microcracks or dehydration induced by mechanical fatigue can interrupt ion pathways, linking conductivity decay directly to structural durability.</p>
        </sec>
        <sec id="sec2-4-2">
          <title>Electronically conductive hydrogels</title>
          <p>Electronically conductive hydrogels rely on electron transport through embedded conductive phases within an otherwise insulating polymer matrix. This is commonly achieved by introducing conductive fillers such as CNTs<sup>[<xref ref-type="bibr" rid="B78">78</xref>]</sup>, graphene<sup>[<xref ref-type="bibr" rid="B127">127</xref>]</sup>, or metallic nanoparticles<sup>[<xref ref-type="bibr" rid="B128">128</xref>]</sup>, that form percolated networks or continuous conductive pathways. When a sufficient filler concentration is reached, electrons can hop between adjacent fillers or travel along interconnected networks under an electric field. For instance, graphene sheets dispersed in a PVA hydrogel can overlap to form conductive channels, enabling efficient electron transport<sup>[<xref ref-type="bibr" rid="B127">127</xref>]</sup>. The conductivity of electronically conductive hydrogels depends strongly on filler type, loading level, dispersion quality, and interfacial interactions with the polymer network. Well-dispersed fillers with strong interfacial bonding facilitate continuous conductive pathways, whereas aggregation or poor compatibility disrupts electron transport. In addition, the hydrogel’s network flexibility and porosity influence the stability of conductive networks during deformation. Large strains or repeated fatigue cycles may fracture conductive bridges, showing how mechanical resilience and electrical performance are inherently coupled.</p>
        </sec>
        <sec id="sec2-4-3">
          <title>Hybrid conductive hydrogels</title>
          <p>Hybrid conductive hydrogels combine ionic and electronic conduction mechanisms by simultaneously incorporating mobile ions and electronically conductive components within a single hydrogel matrix. In such systems, ionic species migrate through hydrated polymer domains, while electrons are transported through interconnected conductive networks<sup>[<xref ref-type="bibr" rid="B129">129</xref>]</sup>. For example, sodium polyacrylate can provide ionic conduction via dissociated Na<sup>+</sup> ions, whereas polyaniline (PANI) embedded in the same matrix enables electronic conduction through percolated networks<sup>[<xref ref-type="bibr" rid="B130">130</xref>]</sup>. The coexistence of these two charge transport pathways results in synergistic conductive behavior. The relative contribution of ionic and electronic conduction can be tuned by adjusting the composition ratio, dispersion state, and interactions between the ionic and electronic components. Environmental factors such as temperature and humidity further modulate performance by influencing ion mobility and the integrity of electronic networks. While dual pathways provide redundancy, mechanical damage such as crack propagation or network collapse can simultaneously impair both ionic and electronic channels, underscoring the need for architectures that balance conductivity with fatigue resistance<sup>[<xref ref-type="bibr" rid="B131">131</xref>]</sup>.</p>
          <p>In summary, fatigue performance and environmental stability of soft materials in humid, thermal, and saline environments are governed by the coupled effects of moisture migration, ionic interactions, and thermally activated processes. Although substantial progress has been achieved in enhancing fatigue resistance and environmental adaptability, several challenges remain. These include achieving simultaneous optimization of conductivity, flexibility, and durability under high humidity and high salt conditions, establishing standardized metrics for quantitative evaluation of structural reversibility during dry-wet cycling, and developing <italic>in situ</italic> monitoring techniques capable of tracking aging mechanisms during long term operation.</p>
          <p>Future research should focus on intelligent and adaptive material systems supported by <italic>in situ</italic> characterization tools such as Raman spectroscopy and atomic force microscope-infrared (AFM IR) spectroscopy to elucidate microstructural evolution during service<sup>[<xref ref-type="bibr" rid="B132">132</xref>,<xref ref-type="bibr" rid="B133">133</xref>]</sup>. Integration of machine learning models to predict lifetime performance based on coupled environmental and mechanical inputs will further enable rational design and engineering scale deployment of durable, high-performance soft functional materials.</p>
        </sec>
      </sec>
    </sec>
    <sec id="sec3">
      <title>FABRICATION AND SCALABILITY STRATEGIES</title>
      <sec id="sec3-1">
        <title>Assembly strategies towards soft hydrogels</title>
        <p>In view of their high-water content and mechanically compliant properties, hydrogels are incompatible with the high-temperature and high-vacuum processing methods typically employed in the fabrication of conventional rigid electronics<sup>[<xref ref-type="bibr" rid="B134">134</xref>-<xref ref-type="bibr" rid="B136">136</xref>]</sup>. As a result, innovative manufacturing techniques have been created specifically for hydrogel-based bioelectronics. This section reviews these methods, such as solvent casting, layer-by-layer (LbL) assembly, photolithography, laser-assisted patterning, and screen printing, 3D printing technique [<xref ref-type="table" rid="t3">Table 3</xref>].</p>
        <table-wrap id="t3">
          <label>Table 3</label>
          <caption>
            <p>Fabrication strategies for robust hydrogels used in flexible bio-integrated devices</p>
          </caption>
          <table frame="hsides" rules="groups">
            <thead>
              <tr>
                <td style="border-bottom:1;">
                  <bold>Strategies</bold>
                </td>
                <td style="border-bottom:1;">
                  <bold>Principle</bold>
                </td>
                <td style="border-bottom:1;">
                  <bold>Achievable structures</bold>
                </td>
                <td style="border-bottom:1;">
                  <bold>Advantages</bold>
                </td>
                <td style="border-bottom:1;">
                  <bold>Representative applications</bold>
                </td>
                <td style="border-bottom:1;">
                  <bold>Ref.</bold>
                </td>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td>Free-radical polymerization</td>
                <td>Free radical-initiated monomer crosslinking into 3D networks</td>
                <td>Bulk, thin films and micro-patterned</td>
                <td>Simple, fast, controllable and scalable</td>
                <td>Flexible electrodes and tissue scaffolds</td>
                <td>[<xref ref-type="bibr" rid="B137">137</xref>]</td>
              </tr>
              <tr>
                <td>Click chemistry polymerization</td>
                <td>Specific click reactions form covalent networks</td>
                <td>Precise, core-shell and functionalized</td>
                <td>Mild, specific and biocompatible</td>
                <td>Injectable adhesives and glucose sensors</td>
                <td>[<xref ref-type="bibr" rid="B138">138</xref>]</td>
              </tr>
              <tr>
                <td>Double-network fabrication</td>
                <td>Two interpenetrating networks dissipate energy</td>
                <td>Tough bulk and flexible films</td>
                <td>Tough, stretchable and fatigue-resistant</td>
                <td>Wearable sensors and artificial skin</td>
                <td>[<xref ref-type="bibr" rid="B139">139</xref>]</td>
              </tr>
              <tr>
                <td>Electrochemical polymerization</td>
                <td>Monomer polymerization on electrodes via electric field</td>
                <td>Electrode films and conductive composites</td>
                <td>Good adhesion, controllable and conductive</td>
                <td>Neural and EMG sensors</td>
                <td>[<xref ref-type="bibr" rid="B140">140</xref>]</td>
              </tr>
              <tr>
                <td>3D printing</td>
                <td>LbL precursor deposition for custom 3D structures</td>
                <td>Custom porous and personalized devices</td>
                <td>Precise, customizable and multi-material</td>
                <td>Personalized sensors and cartilage scaffolds</td>
                <td>[<xref ref-type="bibr" rid="B141">141</xref>]</td>
              </tr>
              <tr>
                <td>Ionic crosslinking</td>
                <td>Electrostatic interactions form physical networks</td>
                <td>Injectable, bulk and tunable films</td>
                <td>Mild, fast, non-toxic and injectable</td>
                <td>Wound dressings and drug carriers</td>
                <td>[<xref ref-type="bibr" rid="B142">142</xref>]</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn>
              <p>LbL: Layer-by-layer; EMG: electromyogram.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>Solvent casting is a commonly used molding process. After dissolving or dispersing the base materials and functional additives in a solvent, the mixture is cast into a mold and the solvent is permitted to evaporate, leading to hydrogel formation<sup>[<xref ref-type="bibr" rid="B143">143</xref>,<xref ref-type="bibr" rid="B144">144</xref>]</sup>. For direct fabrication of conductive hydrogels bioelectronics using templating, hydrogel-based precursors are poured into a specially designed mold, ensuring precise alignment with the intended patterns. The hydrogel precursor is then cured in place through methods such as chemical crosslinking, ultraviolet (UV) polymerization, air drying, or other curing techniques, which solidify the hydrogel network. This technique is low-cost and ideal for the large-scale preparation of simple hydrogel architectures, which also allows for distribution of nanoparticles or other functional elements throughout the hydrogel, while the evaporation process helps control both the material’s microscopic structure and overall performance. For example, Chen <italic>et al.</italic> in <xref ref-type="fig" rid="fig5">Figure 5A</xref> introduced a one-step method that uses hydronium ion-driven dissociation along with chemical cross-linking to quickly dissolve and modify cellulose, resulting in highly organized and durable cellulose films<sup>[<xref ref-type="bibr" rid="B145">145</xref>]</sup>. In their process, an organic acid creates a strong driving force for H<sup>+</sup> release, which, together with H<sub>2</sub>SO<sub>4</sub>, triggers both the dissolution and derivatization of cellulose. Similarly, Han <italic>et al.</italic> in <xref ref-type="fig" rid="fig5">Figure 5B</xref> developed a conductive, soft, and transparent hydrogel by integrating biocompatible PVA and poly(vinylpyrrolidone) (PVP) chains<sup>[<xref ref-type="bibr" rid="B146">146</xref>]</sup>. This hydrogel features an extremely low modulus, excellent resilience, and high transparency. Additionally, polydopamine nanoparticles are embedded within the hydrogel structures, greatly improving their adhesive strength and electrical conductivity, all while maintaining superior transparency. Overall, solvent casting remains one of the most widely used techniques for making hydrogel electronics, offering extensive material compatibility with few limitations on material types. However, constraints related to mold size and difficulties in separating the finished product can limit large-scale manufacturing and high-precision production of hydrogel bioelectronics<sup>[<xref ref-type="bibr" rid="B147">147</xref>,<xref ref-type="bibr" rid="B148">148</xref>]</sup>. However, despite its simplicity and material versatility, solvent casting is limited in achieving high-resolution patterning and precise structural control, which restricts its application in miniaturized and high-density bioelectronic systems.</p>
        <fig id="fig5" position="float">
          <label>Figure 5</label>
          <caption>
            <p>(A) One-pot strategy for dissolving cellulose hydrogels<sup>[<xref ref-type="bibr" rid="B145">145</xref>]</sup>. Copyright 2024, American Chemical Society; (B) Hydrogels from PVA-PVP-PDA NPs materials<sup>[<xref ref-type="bibr" rid="B146">146</xref>]</sup>. Copyright 2023, Wiley-VCH; (C) The ionogel via the LbL assembly approach<sup>[<xref ref-type="bibr" rid="B155">155</xref>]</sup>; Copyright 2025, Wiley-VCH. PVA: Poly(vinyl alcohol); PVP: poly(vinylpyrrolidone); PDA: polydopamine; NPs: nanoparticles; LbL: layer-by-layer; RF: radio frequency.</p>
          </caption>
          <graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="ss6067.fig.5.jpg" />
        </fig>
        <p>LbL assembly enables highly precise control over the composition, thickness, and interfacial characteristics of materials, particularly at the nanoscale<sup>[<xref ref-type="bibr" rid="B149">149</xref>,<xref ref-type="bibr" rid="B150">150</xref>]</sup>. In this approach, functional components are deposited onto a substrate sequentially, one layer at a time, with each layer stabilized through interactions such as hydrogen bonding or covalent bonding<sup>[<xref ref-type="bibr" rid="B151">151</xref>,<xref ref-type="bibr" rid="B152">152</xref>]</sup>. Electrostatic forces are crucial for maintaining the stability of these multilayer structures and allow for fine-tuning of the coating’s thickness and surface features. With LbL assembly, it’s possible to create bilayer or multilayer structures on a substrate, each with unique functionalities<sup>[<xref ref-type="bibr" rid="B153">153</xref>,<xref ref-type="bibr" rid="B154">154</xref>]</sup>. For instance, Thapaliya <italic>et al.</italic> in <xref ref-type="fig" rid="fig5">Figure 5C</xref> developed polyelectrolyte membranes with high charge density by alternately layering polyions with specially designed functional groups onto a neutral ionogel membrane, leveraging the ionogel’s inherent ionic nature for easy interfacial modification<sup>[<xref ref-type="bibr" rid="B155">155</xref>]</sup>. The LbL technique enables precise, molecular-level control over the membrane’s structure, allowing for the integration of functional groups specifically suited for lithium metal battery applications. As a result, these LbL-assembled polyelectrolytes demonstrate enhanced mechanical strength and electrochemical stability, making them ideal for use in high-voltage environments<sup>[<xref ref-type="bibr" rid="B156">156</xref>]</sup>.</p>
        <p>Creating hydrogel bioelectronics with photolithography involves applying a hydrogel precursor onto a substrate and then exposing it to UV light through a photomask to form a specific pattern<sup>[<xref ref-type="bibr" rid="B157">157</xref>,<xref ref-type="bibr" rid="B158">158</xref>]</sup>. Once exposed, the photoresist layer is removed, revealing the patterned hydrogel structures underneath. However, because hydrogels contain a lot of water and tend to swell when they come into contact with the precursor solution, overexposure between neighboring features often restricts the resolution to around 100 µm. As a result, traditional photolithography has difficulty achieving high-precision and direct patterning of conductive hydrogels<sup>[<xref ref-type="bibr" rid="B158">158</xref>]</sup>. For instance, Liu <italic>et al.</italic> in <xref ref-type="fig" rid="fig6">Figure 6A</xref> and <xref ref-type="fig" rid="fig6">B</xref> created a hydrogel-based electrode with a resolution as fine as 5 µm by applying standard photolithographic patterning to an ion gel [poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS)-ionic liquid (IL) ion gel], which was then converted into a micropatterned hydrogel structure<sup>[<xref ref-type="bibr" rid="B159">159</xref>]</sup>. They effectively solved the problem of uncontrolled swelling in the micropatterned hydrogels by using a solvent exchange process. After curing the precursor with UV light, the resulting patterns showed excellent elasticity, flexibility, and chemical stability in most solvents. Compared to other fabrication techniques, photolithography enables the production of hydrogel bioelectronics with extremely detailed features, reaching down to just a few micrometers<sup>[<xref ref-type="bibr" rid="B160">160</xref>,<xref ref-type="bibr" rid="B161">161</xref>]</sup>. However, this method is typically limited to making two-dimensional planar patterns, and any changes to the electrode design require a new photomask, which can lower efficiency and raise costs<sup>[<xref ref-type="bibr" rid="B160">160</xref>,<xref ref-type="bibr" rid="B161">161</xref>]</sup>. Additionally, the light sources used in photolithography may damage the hydrogel network, especially in systems that include living components like enzymes or bacteria.</p>
        <fig id="fig6" position="float">
          <label>Figure 6</label>
          <caption>
            <p>(A) Lithographically assisted method for hydrogels. cellulose hydrogels; (B) Stepwise depiction of hydrogel lithography. (A and B) are reprinted with permission from Ref.<sup>[<xref ref-type="bibr" rid="B159">159</xref>]</sup>. Copyright 2019, Springer Nature; (C) Laser technology for the dehydrated hydrogel film<sup>[<xref ref-type="bibr" rid="B160">160</xref>]</sup>. Copyright 2023, Springer Nature; (D) Laser-induced method for conducting polymer<sup>[<xref ref-type="bibr" rid="B163">163</xref>]</sup>. Copyright 2022, The American Association for the Advancement of Science; (E) A transferable temporary tattoo<sup>[<xref ref-type="bibr" rid="B169">169</xref>]</sup>. Copyright 2022, Wiley-VCH; (F) Direct-ink-writable hydrogel systems<sup>[<xref ref-type="bibr" rid="B174">174</xref>]</sup>. Copyright 2024, Elsevier; (G) 3D-printing regenerated cellulose hydrogels<sup>[<xref ref-type="bibr" rid="B175">175</xref>]</sup>. Copyright 2022, Elsevier. PEDOT:PSS: Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate); IL: ionic liquid; MECH: micropatterned electrically conductive hydrogel; PFPE-DMA: UV-crosslinked dimethacrylate-functionalized perfluoropolyether; UV: ultraviolet; iCVD: initiated chemical vapor deposition; EC: ethylcellulose; SA: sodium alginate; MMT: montmorillonite; CNF: cellulose nanofiber.</p>
          </caption>
          <graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="ss6067.fig.6.jpg" />
        </fig>
        <p>Laser-assisted patterning is a non-contact technique that has become a versatile tool for working with a variety of materials, including metals, glass, and polymers<sup>[<xref ref-type="bibr" rid="B162">162</xref>]</sup>. This approach uses high-energy laser ablation to process materials, offering outstanding precision and control during fabrication. For patterning hydrogel electronics, a tightly focused laser beam is used to cut and shape hydrogel substrates with great accuracy, allowing for the creation of intricate patterns and structures. When the laser hits the surface of hydrogel films, the generated thermal energy causes the material to sublimate along the designated micro-patterns or channels in <xref ref-type="fig" rid="fig6">Figure 6C</xref><sup>[<xref ref-type="bibr" rid="B160">160</xref>]</sup>. However, the localized heating on the hydrogel surface can impact both the resolution and quality of the process due to the potential for thermal damage. By adjusting the laser’s beam size and intensity, the width of the patterned features can be precisely managed. Won <italic>et al.</italic> in <xref ref-type="fig" rid="fig6">Figure 6D</xref> used a laser-induced innovative, ultrafast, and cytocompatible digital patterning process for PEDOT:PSS hydrogel structures<sup>[<xref ref-type="bibr" rid="B163">163</xref>]</sup>. By selectively scanning materials with a laser, they were able to improve both the hydrogel’s electrical performance and water stability<sup>[<xref ref-type="bibr" rid="B163">163</xref>]</sup>. These PEDOT:PSS composites demonstrated high conductivity (670 S·cm<sup>-1</sup>) and achieved fine patterning resolution down to 6 μm in aqueous environments.</p>
        <p>Screen printing is a robust industrial method used to produce bold, long-lasting designs on a wide variety of products at scale<sup>[<xref ref-type="bibr" rid="B164">164</xref>,<xref ref-type="bibr" rid="B165">165</xref>]</sup>. Typically, this process involves transferring hydrogel inks onto a substrate using a pre-patterned screen that serves as a stencil to define the desired shapes. A blade or squeegee spreads the hydrogel ink across the screen, pushing the ink through the open areas and depositing it precisely onto the substrate. The pressure from the blade ensures even ink coverage, while the screen’s pattern guarantees accurate design transfer. After printing, the inks are cured or dried to form the final printed structures<sup>[<xref ref-type="bibr" rid="B166">166</xref>,<xref ref-type="bibr" rid="B167">167</xref>]</sup>. For example, Lu <italic>et al.</italic> developed a thin, flexible, and conductive nanocomposite using laser-induced graphene (LIG) micropatterns<sup>[<xref ref-type="bibr" rid="B168">168</xref>]</sup>. To overcome the mechanical difficulties of transferring LIG onto elastomers, they utilized a -196 °C cryogenic transfer procedure, by introducing an ultrathin, adhesive PVA-phytic acid (PA)-honey hydrogel layer for various printed devices<sup>[<xref ref-type="bibr" rid="B168">168</xref>]</sup>. In another example, tattoo-like substrates in <xref ref-type="fig" rid="fig6">Figure 6E</xref> were created by screen printing PEDOT:PSS electrodes, followed by a conformal coating of a pH-sensitive poly(methacrylic acid) (pMAA) hydrogel using initiated chemical vapor deposition, resulting in a fully polymer-based pH skin sensor<sup>[<xref ref-type="bibr" rid="B169">169</xref>]</sup>. The performance of this pH sensor tattoo was thoroughly evaluated, including its usability, structure, and pH responsiveness, with special attention to swelling behavior and dielectric properties.</p>
        <p>3D printing technique allows for the LbL construction of materials using computer-generated models<sup>[<xref ref-type="bibr" rid="B170">170</xref>,<xref ref-type="bibr" rid="B171">171</xref>]</sup>. Compared to traditional manual or mold-based techniques, 3D/4D printing provides precise control over the creation of varied shapes<sup>[<xref ref-type="bibr" rid="B172">172</xref>]</sup>. In direct ink writing (DIW) process, specially formulated inks are extruded through a nozzle along a programmed path, which needs to be fluid enough to flow easily through the nozzle, but sturdy enough to maintain its shape once deposited<sup>[<xref ref-type="bibr" rid="B173">173</xref>]</sup>. For instance, researchers have developed a biobased ternary hydrogel made from CNF, sodium alginate (SA), and calcium montmorillonite (Ca-MMT) that serves as an all-in-one, 3D-printable DIW ink through a single-step <italic>in situ</italic> physical gelation process in <xref ref-type="fig" rid="fig6">Figure 6F</xref><sup>[<xref ref-type="bibr" rid="B174">174</xref>]</sup>. In another work, Yuan <italic>et al.</italic> introduced a high-performance cellulose ink with outstanding thixotropic properties, striking a careful balance between ease of extrusion and the ability to support itself<sup>[<xref ref-type="bibr" rid="B175">175</xref>]</sup>. Consequently, the optimized cellulose ink makes it possible to print objects with any complex shape, fully three-dimensional forms like anatomical hearts, ears, rabbits, lamps, and cups, while achieving detailed microstructures with a resolution of 250 μm in <xref ref-type="fig" rid="fig6">Figure 6G</xref>.</p>
      </sec>
      <sec id="sec3-2">
        <title>Interface design and packaging technology</title>
        <sec id="sec3-2-1">
          <title>Importance of interface matching</title>
          <p>The long-term performance of soft hydrogels in bio-integrated devices depends strongly on interfacial adhesion to skin, tissues, or soft robotic structures<sup>[<xref ref-type="bibr" rid="B2">2</xref>]</sup>. Hydrogels are highly hydrated networks with low modulus and high permeability, yet they must interface with biological substrates that are persistently wet, dynamic, and chemically heterogeneous<sup>[<xref ref-type="bibr" rid="B129">129</xref>]</sup>. Without proper interface matching, even advanced bulk materials cannot maintain stable system functions during real operation<sup>[<xref ref-type="bibr" rid="B176">176</xref>]</sup>.</p>
          <p>A major challenge arises from insufficient adhesion in fluid-dominated environments such as sweat, gastric acid, and tears<sup>[<xref ref-type="bibr" rid="B177">177</xref>]</sup>. Mechanical mismatch between hydrogel layers and viscoelastic tissues further accelerates delamination under cyclic motion or long-term wear<sup>[<xref ref-type="bibr" rid="B178">178</xref>]</sup>. Many commercial packaging films are either fully impermeable, causing irritation, or contain reactive glues that raise safety concerns<sup>[<xref ref-type="bibr" rid="B179">179</xref>]</sup>. The objective of interface design is therefore to construct bonding zones that are robust, reversible, and biocompatible, enabling conformal integration of hydrogels under physiological conditions.</p>
        </sec>
        <sec id="sec3-2-2">
          <title>Bioinspired adhesion strategies</title>
          <p>Physical strategies are inspired by the way organisms maintain attachment on naturally moist boundaries<sup>[<xref ref-type="bibr" rid="B180">180</xref>]</sup>. Hierarchical micro and nanostructures, exemplified by gecko-like fibrillar arrays<sup>[<xref ref-type="bibr" rid="B181">181</xref>]</sup> and crab claw-resembling interlocking textures<sup>[<xref ref-type="bibr" rid="B182">182</xref>]</sup>, create multipoint contact and efficient energy dissipation to help soft materials adapt to irregular tissue surfaces. For example, Hu <italic>et al.</italic> fabricated bioinspired hierarchical architectures that significantly improved contact-sensible adhesion performance under dynamic loading [<xref ref-type="fig" rid="fig7">Figure 7A</xref>]<sup>[<xref ref-type="bibr" rid="B183">183</xref>]</sup>. These architectures convert unavoidable fluid layers such as sweat<sup>[<xref ref-type="bibr" rid="B94">94</xref>]</sup>, gastric juice<sup>[<xref ref-type="bibr" rid="B184">184</xref>]</sup>, or <InlineParagraph>tears<sup>[<xref ref-type="bibr" rid="B185">185</xref>]</sup></InlineParagraph> into supportive liquid bridges, increasing peeling resistance while alleviating mechanical mismatch. Consistent with this concept, Yuk <italic>et al.</italic> reported a tough hydrogel adhesive that leveraged interfacial water rather than excluding it, achieving durable adhesion on wet biological tissues and implanted devices [<xref ref-type="fig" rid="fig7">Figure 7B</xref>]<sup>[<xref ref-type="bibr" rid="B186">186</xref>]</sup>. Li <italic>et al.</italic> engineered a polyphenol-based adhesive hydrogel capable of forming dynamic hydrogen bonding and metal coordination with tissue surfaces, enabling repeatable wet adhesion and on-demand debonding [<xref ref-type="fig" rid="fig7">Figure 7C</xref>]<sup>[<xref ref-type="bibr" rid="B187">187</xref>]</sup>. In clinical practice, patterned films<sup>[<xref ref-type="bibr" rid="B188">188</xref>]</sup> and porous tapes<sup>[<xref ref-type="bibr" rid="B189">189</xref>]</sup> based on this philosophy have been explored to improve the comfort and removal safety of wound dressings and wearable sensors.</p>
          <fig id="fig7" position="float">
            <label>Figure 7</label>
            <caption>
              <p>Bioinspired strategies and interfacial mechanisms for hydrogel-based tissue adhesion. (A) Bioinspiration from natural adhesive systems, where hierarchical surface structures such as gecko-inspired architectures provide design principles for contact-mediated adhesion across multiple length scales<sup>[<xref ref-type="bibr" rid="B183">183</xref>]</sup>. Copyright 2022, Wiley-VCH; (B) Bioinspired adhesive microstructures integrated into engineered devices, where mushroom-shaped microstructures combined with compliant substrates and conductive electrodes enable conformal contact and enhanced interfacial adhesion<sup>[<xref ref-type="bibr" rid="B186">186</xref>]</sup>. Copyright 2019, Springer Nature; (C) Mechanisms of hydrogel-based tissue adhesion, including polymer network formation, interfacial bridging, and molecular interactions such as covalent bonding, ionic coordination, and polymer entanglement that contribute to strong adhesion and energy dissipation at the tissue–material interface<sup>[<xref ref-type="bibr" rid="B187">187</xref>]</sup>. Copyright 2017, The American Association for the Advancement of Science. PET: Polyethylene terephthalate; DST: double-sided tape.</p>
            </caption>
            <graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="ss6067.fig.7.jpg" />
          </fig>
          <p>Chemical inspirations provide a complementary molecular route<sup>[<xref ref-type="bibr" rid="B190">190</xref>]</sup>. Networks rich in hydrogen bonds and aromatic groups interact with interfacial proteins and mucin glycoproteins, resembling transient biological bonding<sup>[<xref ref-type="bibr" rid="B191">191</xref>,<xref ref-type="bibr" rid="B192">192</xref>]</sup>. Polyphenols illustrate how metal coordination and dynamic covalent bonds can reinforce adhesion without sacrificing tolerance, allowing application-oriented balance between residence and safe removal<sup>[<xref ref-type="bibr" rid="B193">193</xref>]</sup>. Such adhesion must be defined by therapeutic outcomes rather than maximal strength at all costs.</p>
        </sec>
        <sec id="sec3-2-3">
          <title>Stability in extreme environments</title>
          <p>Many conventional hydrogels rely on ester- or amide-based cross-linking pathways that can be vulnerable to hydrolysis in strongly acidic or high-salt media. Cleavage of cross-linking nodes within the backbone leads to decline in modulus, excessive swelling, and eventual structural failure. For example, Sun <italic>et al.</italic> showed that ionically crosslinked hydrogels rapidly lost mechanical integrity and adhesion under high ionic strength conditions due to charge screening and network dissociation<sup>[<xref ref-type="bibr" rid="B62">62</xref>]</sup>. Protonation and ionic screening at tissue interfaces further weaken electrostatic attraction and hydrogen-bonding, giving rise to short-lived adhesion and delamination<sup>[<xref ref-type="bibr" rid="B194">194</xref>]</sup>. These phenomena are particularly problematic in the gastrointestinal tract, sweat-rich chronic wounds, and the ocular surface dominated by tear fluids<sup>[<xref ref-type="bibr" rid="B195">195</xref>]</sup>. Addressing this challenge, Yang <italic>et al.</italic> developed a mucus-inspired hydrogel with protonation-driven adhesion that remained structurally stable and strongly adhesive under highly acidic conditions (pH ≈ 2), enabling effective esophageal tissue repair <italic>in vivo</italic> [<xref ref-type="fig" rid="fig8">Figure 8A</xref>]<sup>[<xref ref-type="bibr" rid="B196">196</xref>]</sup>. Therefore, reliable performance requires dual or dynamically reinforced networks incorporating chemically inert motifs, so that resistance to chemical attack and maintenance of interfacial coupling can be achieved simultaneously.</p>
          <fig id="fig8" position="float">
            <label>Figure 8</label>
            <caption>
              <p>Bioinspired hydrogel design and electronic architectures for biointegrated systems. (A) Design of a mucus-inspired ultra-stable hydrogel integrating ELR-IK24 proteins, tannic acid, and HDI to achieve acid buffering, wet adhesion, and enhanced structural stability<sup>[<xref ref-type="bibr" rid="B196">196</xref>]</sup>. Copyright 2025, Elsevier; (B) Auxetic kirigami-based electronic architecture, where dumbbell-shaped kirigami patterns enable stretchable electronic interfaces integrating Au electrodes and PI layers on PDMS substrates for conformal biointegration and stable electrical performance<sup>[<xref ref-type="bibr" rid="B198">198</xref>]</sup>. Copyright 2021, The American Association for the Advancement of Science. HDI: Hexamethylene diisocyanate; PI: polyimide; PDMS: polydimethylsiloxane; ELR: elastin-like recombinant.</p>
            </caption>
            <graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="ss6067.fig.8.jpg" />
          </fig>
        </sec>
        <sec id="sec3-2-4">
          <title>Encapsulation and evaporation suppression</title>
          <p>Interface hydration must be preserved during exposure to air, as dehydration alters ionic mobility, interfacial impedance, and consequently sensing accuracy<sup>[<xref ref-type="bibr" rid="B197">197</xref>]</sup>. Along this line, Yeon <italic>et al.</italic> demonstrated that sweat pore-inspired perforated e-skins effectively mitigate sweat accumulation at the skin-device interface, thereby preserving conformal contact and long-term sensing stability during daily activities [<xref ref-type="fig" rid="fig8">Figure 8B</xref>]<sup>[<xref ref-type="bibr" rid="B198">198</xref>]</sup>. Two complementary strategies are commonly used. Breathable yet waterproof polymeric membranes serve as physical barriers to evaporation while permitting gas and metabolite diffusion<sup>[<xref ref-type="bibr" rid="B199">199</xref>]</sup>. Hydrophobic or mucus-mimicking surface coatings provide additional regulation of interfacial water activity, enabling consistent permeability and signal stability under long-term wearing<sup>[<xref ref-type="bibr" rid="B200">200</xref>]</sup>. The combination of encapsulation engineering and biomimetic skins has emerged as a practical design principle for translating soft hydrogels into continuous monitoring platforms.</p>
        </sec>
        <sec id="sec3-2-5">
          <title>Multifunctional integration and system compatibility</title>
          <p>Bio-interfaces are evolving from single adhesive layers to hubs for electrical and therapeutic exchange<sup>[<xref ref-type="bibr" rid="B201">201</xref>]</sup>. Conductive zones must support reliable percolation for sensors, while elastic networks demand low filler loading to preserve flexibility. Integration introduces challenges including sensing crosstalk and mismatch with flexible electronics or clinical workflows<sup>[<xref ref-type="bibr" rid="B202">202</xref>]</sup>. Therefore, molecular composition, microstructure, and encapsulation should be co-optimized to ensure predictable transport and stable system compatibility.</p>
          <p>Progress toward clinical translation will rely on three dimensions. Programmable stimuli-responsive interfaces with reversible adhesion will address dynamic wet boundaries. AI-assisted prediction of interfacial lifetime could reduce empirical trial in material selection. Standardized testing protocols and long-term durability assessments will enable cross-laboratory comparison and regulatory evaluation. Convergence of these routes will determine how bioinspired soft interfaces mature into reliable wearable and implantable technologies.</p>
        </sec>
      </sec>
    </sec>
    <sec id="sec4">
      <title>EMERGING TRENDS AND CROSS-CUTTING APPLICATION SCENARIOS</title>
      <sec id="sec4-1">
        <title>Stimuli-responsive functionalization of soft hydrogels</title>
        <sec id="sec4-1-1">
          <title>Physical stimulus response</title>
          <p>By incorporating photothermal nanomaterials (such as Mxene, polydopamine, and gold nanorods), hydrogels can efficiently convert light energy of specific wavelengths (primarily near-infrared) into heat<sup>[<xref ref-type="bibr" rid="B203">203</xref>]</sup>, thereby inducing localized thermally triggered volume phase transitions, which in turn generate programmed bending, curling, or grasping motions<sup>[<xref ref-type="bibr" rid="B204">204</xref>,<xref ref-type="bibr" rid="B205">205</xref>]</sup>. Inspired by the phototropic behavior of <InlineParagraph>sunflowers,</InlineParagraph> Qin <italic>et al.</italic> developed a bionic sunflower using a light-responsive soft hydrogel that autonomously bends towards a light source, enabling a photocatalytic disk to maintain near-vertical alignment for highly efficient H<sub>2</sub>O<sub>2</sub> production by maximizing light energy capture<sup>[<xref ref-type="bibr" rid="B206">206</xref>]</sup>. Thermoresponsive hydrogels, exemplified by poly(N-isopropylacrylamide) (PNIPAM, also known as PNIPAAm), undergo volume transitions driven by the temperature-dependent balance between hydrophilic and hydrophobic interactions of polymer chains<sup>[<xref ref-type="bibr" rid="B207">207</xref>,<xref ref-type="bibr" rid="B208">208</xref>]</sup>. Chung <italic>et al.</italic> discovered that incorporating NaClO<sub>4</sub> during polymerization creates phase-separated, porous structures in PNIPAAm hydrogels, enabling ultrafast and large volume shrinkage upon heating. This significantly enhanced thermoresponsiveness, which is critical for applications like soft actuators and drug delivery systems, overcomes the slow deformation limitation of conventional hydrogels [<xref ref-type="fig" rid="fig9">Figure 9A</xref>]<sup>[<xref ref-type="bibr" rid="B209">209</xref>]</sup>. Furthermore, aligning superparamagnetic nanoparticles (e.g., Fe<sub>3</sub>O<sub>4</sub>) within hydrogel networks enables heat generation under alternating magnetic fields or direct actuation under gradient magnetic fields<sup>[<xref ref-type="bibr" rid="B210">210</xref>,<xref ref-type="bibr" rid="B211">211</xref>]</sup>. Preprogramming the spatial distribution of magnetic particles allows complex three-dimensional deformations and directional motion<sup>[<xref ref-type="bibr" rid="B212">212</xref>]</sup>, offering great potential in targeted drug delivery and wireless control of microrobots. Additionally, constructing ionic concentration gradients or incorporating electroactive polymers within hydrogels allows electric fields to induce ion migration, local pH changes, or redox reactions of polymer chains, resulting in asymmetric swelling or shrinkage. This mechanism provides rapid responsiveness, making it suitable for artificial muscles and microfluidic valves<sup>[<xref ref-type="bibr" rid="B213">213</xref>]</sup>.</p>
          <fig id="fig9" position="float">
            <label>Figure 9</label>
            <caption>
              <p>Stimuli-responsive mechanisms, responsivity, and multimodal sensing integration of soft hydrogels. (A) Network structures with phase separation and shrinking kinetics of normal hydrogel (NG) and phase-separated hydrogel (PSG)-1 to PSG-5 after a temperature jump from 20 to 45 °C, showing d<sub>n</sub> <italic>vs.</italic> time with relaxation times from the slopes<sup>[<xref ref-type="bibr" rid="B209">209</xref>]</sup>. Copyright 2021, MDPI; (B) Reversible twisting and recovery of M<sub>1</sub>S<sub>0.5</sub>A<sub>0.5</sub> hydrogel in 0.1 M HCl and NaOH solutions, demonstrating consistent shape-memory behavior over at least 10 cycles<sup>[<xref ref-type="bibr" rid="B218">218</xref>]</sup>. Copyright 2018, Wiley-VCH; (C) Schematic of anisotropic ASPC hydrogel deformation in different solvents, facilitated by rapid water transport through low-tortuosity porous channels<sup>[<xref ref-type="bibr" rid="B219">219</xref>]</sup>. Copyright 2024, Springer Nature; (D) Multistage responsive behavior of CdS photonic crystal organohydrogel<sup>[<xref ref-type="bibr" rid="B228">228</xref>]</sup>. Copyright 2024, Elsevier; (E) The wearable human–machine interaction interface design using hydrogel-based EMG and pressure sensors for an AI-assisted active rehabilitation robotic system<sup>[<xref ref-type="bibr" rid="B259">259</xref>]</sup>. Copyright 2024, Wiley-VCH; (F) A jellyfish-inspired biomimetic hydrogel sensor device for temperature and pressure sensing<sup>[<xref ref-type="bibr" rid="B278">278</xref>]</sup>. Copyright 2025, Wiley-VCH. ASPC: Ag/Sa (sodium alginate)/PNIPAM [poly(N-isopropylacrylamide)]/CNT (carbon nanotube); EMG: electromyogram; PNIPAM: poly(N-isopropylacrylamide); CNT: carbon nanotube; UV: ultraviolet; AIE: aggregation-induced emission; FMG: force myography; FPCB: flexible printed circuit board; PDMS: polydimethylsiloxane.</p>
            </caption>
            <graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="ss6067.fig.9.jpg" />
          </fig>
        </sec>
        <sec id="sec4-1-2">
          <title>Chemical stimulus response</title>
          <p>Chemical responsiveness enables hydrogels to deeply interact with biological microenvironments<sup>[<xref ref-type="bibr" rid="B214">214</xref>,<xref ref-type="bibr" rid="B215">215</xref>]</sup>. Networks containing weak acidic/basic groups (e.g., carboxyl groups in polyacrylic acid (PAA) or amino groups in chitosan) exhibit significant swelling changes in response to environmental pH<sup>[<xref ref-type="bibr" rid="B216">216</xref>,<xref ref-type="bibr" rid="B217">217</xref>]</sup>. For example, Zhang <italic>et al.</italic> developed a polyampholyte hydrogel capable of spontaneous shape-memory cycles and macroscopic motion in response to alternating acidic/alkaline solutions, demonstrating its potential as a soft actuator [<xref ref-type="fig" rid="fig9">Figure 9B</xref>]<sup>[<xref ref-type="bibr" rid="B33">33</xref>,<xref ref-type="bibr" rid="B218">218</xref>]</sup>. Recently, Yao <italic>et al.</italic> developed a solvent-adaptive hydrogel with a layered, constrained honeycomb structure [<xref ref-type="fig" rid="fig9">Figure 9C</xref>]<sup>[<xref ref-type="bibr" rid="B219">219</xref>]</sup>.</p>
        </sec>
        <sec id="sec4-1-3">
          <title>Stimulus-responsive mechanisms</title>
          <p>Volume change represents the most fundamental stimulus-responsive behaviour of hydrogels, primarily driven by abrupt variations in osmotic pressure within the network or significant alterations in polymer-solvent interactions<sup>[<xref ref-type="bibr" rid="B220">220</xref>]</sup>. To transform uniform volumetric changes into directional, programmable deformations (such as bending, twisting, or curling), asymmetry or gradient structures must be introduced within the hydrogel to generate internal stress differences under stimulation<sup>[<xref ref-type="bibr" rid="B221">221</xref>,<xref ref-type="bibr" rid="B222">222</xref>]</sup>. For example, Wu <italic>et al.</italic> researched a novel soft hydrogel system where <italic>in-situ</italic> proton transfer enables programmable shape-morphing under light stimulation, independent of external water exchange<sup>[<xref ref-type="bibr" rid="B223">223</xref>]</sup>. Patterned printing of hydrogels with distinct responsiveness enables programmed two-dimensional to three-dimensional deformations<sup>[<xref ref-type="bibr" rid="B224">224</xref>]</sup>. Chen <italic>et al.</italic> developed a multiprogrammable anisotropic soft hydrogel by embedding magnetically oriented ferromagnetic nanoplates, which exhibits anisotropic volume response with distinct swelling ratios parallel and perpendicular to the alignment direction. This deliberate structural ordering enables the programmable integration of optical, mechanical, and magnetic properties for advanced soft actuators<sup>[<xref ref-type="bibr" rid="B225">225</xref>]</sup>. A typical example involves aligning magnetic nanoparticles along a single direction and fixing them within the network, so that the hydrogel bends predominantly in the vertical direction under magnetic or photothermal actuation<sup>[<xref ref-type="bibr" rid="B225">225</xref>]</sup>. Such preprogrammed anisotropy provides a powerful tool for achieving complex and predictable deformations.</p>
          <p>Building on the concept of volume-dependent transformations, hydrogels can also demonstrate color responses through structural coloration mechanisms. The color response of hydrogels (structural coloration) does not originate from chemical dyes but rather from interference, diffraction, or scattering of light by their internal periodic nanostructures<sup>[<xref ref-type="bibr" rid="B226">226</xref>,<xref ref-type="bibr" rid="B227">227</xref>]</sup>. This coloration dynamically adjusts with changes in nanoscale spacing. For example, Chen <italic>et al.</italic> developed a photochromic organohydrogel that exhibits distinct color changes under UV light due to the reversible molecular conformational switching of naphthalene (Np) groups, enabling dynamic optical properties [<xref ref-type="fig" rid="fig9">Figure 9D</xref>]<sup>[<xref ref-type="bibr" rid="B228">228</xref>]</sup>. When stimuli induce uniform swelling or shrinkage of the hydrogel<sup>[<xref ref-type="bibr" rid="B229">229</xref>]</sup>, the lattice constant (interparticle spacing) changes accordingly, resulting in shifts in the wavelength of Bragg-diffracted light. Macroscopically, this manifests as continuous and reversible color changes. The quantitative relationship between color and stimulus intensity makes such hydrogels ideal candidates for visual sensing applications<sup>[<xref ref-type="bibr" rid="B229">229</xref>]</sup>.</p>
          <p>Expanding beyond optical responses, hydrogels can also exhibit photoelectric effects for energy conversion and sensing. Photoelectric response refers to the ability of materials to generate or modulate electrical signals (current, voltage, or resistance) under illumination<sup>[<xref ref-type="bibr" rid="B230">230</xref>]</sup>. Achieving efficient photoelectric response in hydrogels requires constructing a complete energy conversion pathway, from light harvesting to charge generation and subsequent charge transport<sup>[<xref ref-type="bibr" rid="B231">231</xref>]</sup>. Wu <italic>et al.</italic> developed a self-powered photoelectric sensor based on soft hydrogel diodes doped with photoacid, where the photoelectric response mechanism involves light-induced proton release from the photoacid and subsequent ion migration driven by the built-in electric field of the hydrogel PN junction<sup>[<xref ref-type="bibr" rid="B232">232</xref>]</sup>. The integrating photoelectric units into hydrogel networks could enable self-powered, soft bio-interfaces for wearable sensors or devices.</p>
        </sec>
      </sec>
      <sec id="sec4-2">
        <title>Flexible electronics integration and e-skin</title>
        <p>Flexible e-skin platforms have been widely adopted in wearable and implantable biomedical devices for continuous health monitoring and therapeutic interfacing. In wearable applications, conformal e-skins can laminate onto the epidermis to monitor electrophysiological signals [electrocardiogram (ECG), electromyogram (EMG)]<sup>[<xref ref-type="bibr" rid="B233">233</xref>]</sup>, temperature<sup>[<xref ref-type="bibr" rid="B234">234</xref>]</sup>, strain<sup>[<xref ref-type="bibr" rid="B235">235</xref>]</sup>, and biochemical markers<sup>[<xref ref-type="bibr" rid="B236">236</xref>]</sup>, supporting applications such as smart rings<sup>[<xref ref-type="bibr" rid="B237">237</xref>]</sup>, epidermal patches<sup>[<xref ref-type="bibr" rid="B238">238</xref>]</sup>, and soft rehabilitation monitors<sup>[<xref ref-type="bibr" rid="B239">239</xref>]</sup>. Their intimate skin contact reduces motion artifacts compared with rigid electronics, enabling higher signal-to-noise ratios during daily activities.</p>
        <p>Implantable flexible electronics further push these advantages into <italic>in vivo</italic> environments, including neural probes<sup>[<xref ref-type="bibr" rid="B240">240</xref>]</sup>, cardiac interfaces<sup>[<xref ref-type="bibr" rid="B241">241</xref>]</sup>, and bioelectronic medicine systems. Ultrathin and mechanically compliant devices can follow tissue micromotions, reducing chronic inflammation and fibrotic encapsulation while maintaining stable electrical contact. In both wearable and implantable contexts, the integration of stretchable substrates, soft encapsulation layers, and biocompatible materials is critical for ensuring long-term safety, durability, and functional stability. A key design principle in e-skin integration is mechanical matching between electronic components and biological tissues. Flexible polymers<sup>[<xref ref-type="bibr" rid="B242">242</xref>]</sup>, elastomers<sup>[<xref ref-type="bibr" rid="B243">243</xref>]</sup>, and hydrogel-based substrates<sup>[<xref ref-type="bibr" rid="B244">244</xref>]</sup> are commonly used to achieve low modulus and high stretchability. Conductive elements are engineered using thin metal films<sup>[<xref ref-type="bibr" rid="B245">245</xref>]</sup>, conductive polymers<sup>[<xref ref-type="bibr" rid="B246">246</xref>]</sup>, liquid metals<sup>[<xref ref-type="bibr" rid="B247">247</xref>]</sup>, or nanocomposites<sup>[<xref ref-type="bibr" rid="B248">248</xref>]</sup>, often arranged in serpentine or mesh geometries to accommodate large strains without electrical failure. Multilayer architectures enable the decoupling of sensing, interconnection, and encapsulation functions, allowing for the integration of complex systems while preserving overall softness and conformability. Beyond materials, signal processing and system-level integration are central to the performance of e-skin systems. Soft bio-interfaces are continuously exposed to noise sources arising from motion, sweat, temperature fluctuations, and environmental electromagnetic interference. To address these challenges, e-skin platforms combine optimized electrode-tissue interfaces with low-noise front-end electronics, on-board amplification, and filtering to stabilize signal output<sup>[<xref ref-type="bibr" rid="B249">249</xref>]</sup>. At the interconnection level, bendable electrodes and stretchable interconnects maintain electrical continuity under repeated deformation, while flexible packaging strategies protect sensitive components from moisture and mechanical damage. At the system level, integrating sensing, data acquisition, power management, and wireless communication into compact, flexible architectures reduces parasitic noise and signal loss. The co-design of hardware and signal-processing algorithms enables adaptive noise suppression and artifact rejection, which is particularly important for long-term monitoring and closed-loop therapeutic systems<sup>[<xref ref-type="bibr" rid="B250">250</xref>]</sup>. Overall, flexible electronics integration provides the technological foundation for e-skin systems that are mechanically compliant, electrically stable, and functionally robust. Continued advances in soft materials, stretchable interconnects, and integrated signal processing will further expand the capabilities of e-skin, enabling multifunctional platforms for continuous health monitoring, neural interfacing, and next-generation wearable and implantable medical devices.</p>
        <sec id="sec4-2-1">
          <title>Sensor modalities and performance metrics</title>
          <p>The central mission of flexible electronics and e-skin is to endow machines or prosthetics with sensory capabilities comparable to, or even surpassing, those of natural skin<sup>[<xref ref-type="bibr" rid="B251">251</xref>]</sup>. High-precision and reliable detection of diverse mechanical signals, including stretching, compression, bending, and their derivatives such as pressure and strain, is fundamental to achieving tactile perception, physiological monitoring, and motion feedback<sup>[<xref ref-type="bibr" rid="B252">252</xref>]</sup>. Owing to their soft mechanical properties matching biological tissues, tunable conductivity, and outstanding fracture toughness, soft hydrogels have emerged as ideal materials for constructing the next generation of durable flexible mechanical sensors<sup>[<xref ref-type="bibr" rid="B253">253</xref>,<xref ref-type="bibr" rid="B254">254</xref>]</sup>. Based on their working mechanisms, these sensors can be categorized into force/pressure sensors, strain sensors, and multifunctional integrated sensors, each designed to accurately detect tension, compression, bending, and pressure signals<sup>[<xref ref-type="bibr" rid="B255">255</xref>-<xref ref-type="bibr" rid="B258">258</xref>]</sup>.</p>
          <p>Force and pressure sensors are primarily employed to detect normal forces or pressures perpendicular to the device surface<sup>[<xref ref-type="bibr" rid="B255">255</xref>,<xref ref-type="bibr" rid="B256">256</xref>]</sup>. Wang <italic>et al.</italic> developed a multimodal hydrogel-based sensing system that integrates EMG and force myography (FMG) signals, leveraging a macroporous Foam-PAM hydrogel pressure sensor to detect subtle muscle forces for active rehabilitation in human-machine interfaces [<xref ref-type="fig" rid="fig9">Figure 9E</xref>]<sup>[<xref ref-type="bibr" rid="B259">259</xref>]</sup>. In addition, Rahman <italic>et al.</italic> discovered that incorporating zeolitic imidazolate framework-8 (ZIF-8) nanoparticles into a poly(acrylamide)-co-hydroxyethyl acrylate (PAAm-co-HEA) hydrogel significantly enhances its force-responsive properties, enabling the fabrication of a highly stretchable triboelectric nanogenerator (TENG) that effectively converts biomechanical forces into electrical signals for self-powered sensing and energy harvesting<sup>[<xref ref-type="bibr" rid="B260">260</xref>]</sup>. Strain sensors are used to monitor stretching, compression, or bending of surfaces, with outputs typically correlated to strain (ε)<sup>[<xref ref-type="bibr" rid="B261">261</xref>]</sup>. Tensile strain detection is predominantly piezoresistive<sup>[<xref ref-type="bibr" rid="B262">262</xref>]</sup>, when hydrogels are stretched, internal conductive pathways (such as ionic channels or networks of conductive nanofillers) are geometrically elongated and cross-sectional areas reduced, leading to increased resistance (positive strain effect). Soft hydrogels can withstand reversible tensile strains, thereby offering a broad detection range<sup>[<xref ref-type="bibr" rid="B254">254</xref>]</sup>. Their high toughness ensures that even under extreme stretching or localized damage, conductive networks remain continuous, allowing signals to recover. Compression sensing mechanisms overlap with those of normal pressure detection but emphasize volumetric deformation. Porous or foam-like hydrogels are particularly advantageous<sup>[<xref ref-type="bibr" rid="B263">263</xref>,<xref ref-type="bibr" rid="B264">264</xref>]</sup>, upon compression, pore closure densifies conductive pathways, reducing resistance, while capacitance characteristics also change. Bending can be regarded as a composite state of tensile strain on one side and compressive strain on the other<sup>[<xref ref-type="bibr" rid="B261">261</xref>]</sup>. Sensors are typically attached to bendable surfaces, with resistance changes reflecting curvature. Critical factors include interfacial adhesion<sup>[<xref ref-type="bibr" rid="B265">265</xref>,<xref ref-type="bibr" rid="B266">266</xref>]</sup>, ensuring hydrogels deform cooperatively with substrates without delamination.</p>
          <p>Key performance indicators for sensors include sensitivity, detection range, response time, and stability<sup>[<xref ref-type="bibr" rid="B267">267</xref>-<xref ref-type="bibr" rid="B269">269</xref>]</sup>. Sensitivity quantifies the ability of sensors to convert mechanical stimuli (e.g., strain or pressure) into electrical signals (e.g., resistance or capacitance changes), determining resolution and amplification of small stimuli<sup>[<xref ref-type="bibr" rid="B267">267</xref>,<xref ref-type="bibr" rid="B269">269</xref>]</sup>. The high sensitivity of soft hydrogel sensors arises from the synergistic interplay between microstructural features and macroscopic mechanical properties<sup>[<xref ref-type="bibr" rid="B270">270</xref>]</sup>. Detection range is defined by the minimum (lower limit) and maximum (upper limit) stimuli that elicit effective responses. The broad elasticity and structural integrity of soft hydrogels provide a physical basis for extending detection ranges. For instance, a highly cracked hydrogel design that achieves multi-sensing with high sensitivity and a large detection range for soft machines by utilizing the opening and closing of pre-cut cracks to significantly alter current flow<sup>[<xref ref-type="bibr" rid="B271">271</xref>]</sup>. Response time characterizes the ability of sensors to track dynamic or transient mechanical stimuli<sup>[<xref ref-type="bibr" rid="B272">272</xref>]</sup>, which is crucial for monitoring vibrations, speech, high-speed impacts, or physiological pulses. Benefiting from low hysteresis and porous architectures<sup>[<xref ref-type="bibr" rid="B263">263</xref>]</sup>, soft hydrogels typically exhibit superior performance. Stability reflects the ability of sensors to maintain functionality under repeated use and environmental fluctuations, representing a core advantage of soft hydrogels<sup>[<xref ref-type="bibr" rid="B269">269</xref>]</sup>. Their energy dissipation mechanisms, fatigue resistance, and synthetic strategies conferring environmental robustness collectively determine sensor lifespan and reliability. Despite their excellent performance in mechanical sensing, soft hydrogel sensors still face multiple challenges in practical applications<sup>[<xref ref-type="bibr" rid="B83">83</xref>,<xref ref-type="bibr" rid="B273">273</xref>,<xref ref-type="bibr" rid="B274">274</xref>]</sup>. Conventional hydrogels undergo significant water-induced swelling in aqueous environments, leading to structural deformation, mechanical degradation, and signal instability. This limits their reliable use in complex conditions such as underwater sensing or high-humidity environments. In contrast to swelling, hydrogels are also prone to rapid moisture loss in ambient or dry conditions, leading to dehydration within hours. This compromises their mechanical integrity, ionic conductivity, and sensing functionality. Practical applications demand a synergy of features, such as mechanical robustness, high conductivity, self-adhesion, self-healing, biocompatibility, and antimicrobial properties, which are challenging to incorporate into a single hydrogel system.</p>
          <p>One of the primary objectives of flexible sensors based on soft yet robust hydrogels is the construction of biomimetic, multifunctional e-skin<sup>[<xref ref-type="bibr" rid="B275">275</xref>,<xref ref-type="bibr" rid="B276">276</xref>]</sup>. An ideal e-skin system must not only transcend the detection of single mechanical signals but also achieve multimodal environmental perception<sup>[<xref ref-type="bibr" rid="B277">277</xref>]</sup>. Moreover, as an interface in long-term, intimate contact with biological systems, it must exhibit excellent wearing comfort, conformability, and biocompatibility. Owing to their tunable physicochemical properties, mechanical compatibility with tissues, and inherently hydrophilic interfaces, soft hydrogels represent an ideal material platform for this purpose. Recent advances can be reviewed from three perspectives, multimodal sensing integration, conformability, and biocompatibility.</p>
          <p>E-skin must emulate the ability of natural skin to perceive multidimensional information, integrating synchronous or selective responses to stimuli such as temperature, humidity, chemical composition, and tactile signals. The design versatility of soft hydrogels provides unique advantages. Temperature sensing can exploit the temperature dependence of ionic conductivity in hydrogels (following the Arrhenius relationship), enabling a single conductive hydrogel to achieve self-sensing of temperature while monitoring mechanical signals. The working mechanism introduced by Ren <italic>et al.</italic> involves a temperature-sensing schematic where variations in temperature directly influence electrical resistance [<xref ref-type="fig" rid="fig9">Figure 9F</xref>]<sup>[<xref ref-type="bibr" rid="B278">278</xref>]</sup>. This alteration in resistance is subsequently detected by an external circuit, facilitating temperature measurement. This well-defined linear dependence enables precise discrimination between different temperature levels. Humidity sensing relies on the hygroscopic nature of hydrogels, with electrical properties (e.g., ionic conductivity and dielectric constant) closely correlated to ambient humidity<sup>[<xref ref-type="bibr" rid="B279">279</xref>]</sup>. Ding <italic>et al.</italic> developed a groundbreaking self-powered, flexible chemosensor by engineering a smart hydrogel incorporated with zinc and lithium ions, enabling it to reversibly switch between water-rich and water-deficient states<sup>[<xref ref-type="bibr" rid="B280">280</xref>]</sup>. This single device achieves crosstalk-free detection of both oxygen and humidity with remarkable sensitivity (up to 4,170.5 %/% for O<sub>2</sub> and 380.2 %/% RH for humidity) by leveraging a metal-air battery structure where the target molecules selectively act as limiting reactants or catalysts in the oxygen reduction reaction depending on the hydrogel’s state. Chemical sensing can be achieved by immobilizing specific recognition elements (e.g., glucose oxidase, aptamers, or molecularly imprinted polymers) within hydrogel networks. Inspired by human skin, Yun <italic>et al.</italic> developed a novel hydrogel-based sensing platform for two-dimensional imaging of external stimuli like chemicals<sup>[<xref ref-type="bibr" rid="B281">281</xref>]</sup>. This design enables high sensitivity 2D imaging through electrochemiluminescence, representing a significant advance toward biocompatible e-skins that leverage chemical reactions for multi-stimuli detection. Tactile sensing (pressure, strain, shear force) forms the foundation of multimodal perception, yet signal decoupling remains a central challenge. Tao <italic>et al.</italic> developed a self-powered tactile hydrogel sensor featuring a micro-pyramid-patterned double-network ionic organohydrogel, which detects subtle pressure changes through triboelectric signals without an external power supply<sup>[<xref ref-type="bibr" rid="B282">282</xref>]</sup>. This sensor exhibits remarkable sensitivity (45.97 mV·Pa<sup>-1</sup>), a fast response time (~20 ms), and operates reliably across a broad temperature range (-20 to 60 °C). Furthermore, its successful integration into a system that controls electronic devices and a robotic hand by mimicking finger gestures demonstrates significant potential for wearable electronics and human-machine interfaces. Comfort and skin-fitting characteristics are essential requirements for e-skin. Soft hydrogels, through precise tuning of mechanical properties and interfacial characteristics, provide key solutions to this requirement<sup>[<xref ref-type="bibr" rid="B283">283</xref>]</sup>. Chen <italic>et al.</italic> developed a wet-adaptive electronic skin (WADE-skin), highlighting that maintaining biological comfort at the device-skin interface in wet environments is crucial for the long-term, imperceptive wearability of epidermal electronics<sup>[<xref ref-type="bibr" rid="B284">284</xref>]</sup>. Zhang <italic>et al.</italic> developed a porous thermoplastic polyurethane (TPU)/carbon black hydrogel sensor via water vapor-induced phase separation, which exhibited high water vapor transmission rates <InlineParagraph>(≈ 3,800-4,100 g·m<sup>-2</sup>·day),</InlineParagraph> enabling comfortable wear while maintaining multimodal sensing capabilities<sup>[<xref ref-type="bibr" rid="B285">285</xref>]</sup>. Furthermore, Zhou <italic>et al.</italic> researched a strain sensor with an ultra-wide sensing range by forming a porous conductive network in a CNT/TPU composite through salt leaching, enhancing both mechanical and breathable properties<sup>[<xref ref-type="bibr" rid="B286">286</xref>]</sup>.</p>
          <p>Biocompatibility is a paramount requirement for hydrogel-based e-skin to ensure safe, long-term wearability and prevent skin irritation or inflammatory responses, which are common issues with impermeable materials. Ma <italic>et al.</italic> developed a highly permeable and superelastic liquid-metal fibre mat (LMFM) that demonstrated excellent biocompatibility, as confirmed by <italic>in vitro</italic> cell viability tests showing over 95% cell survival and <italic>in vivo</italic> tests on rabbit and human skin showing no significant irritation, making it ideal for monolithic, multi-layered e-skin devices<sup>[<xref ref-type="bibr" rid="B287">287</xref>]</sup>. Additionally, Yan <italic>et al.</italic> developed conductive cellulose-based bio-nanosheet hydrogels by using polydopamine-reduced graphene oxide (GO) as a template for cellulose assembly. This approach resulted in a hydrogel that exhibits remarkable stability under physiological conditions while maintaining excellent electrical functionality and the ability to support cell growth, showcasing its high potential for creating long-term, bio-integrated electronic devices<sup>[<xref ref-type="bibr" rid="B288">288</xref>]</sup>.</p>
        </sec>
      </sec>
      <sec id="sec4-3">
        <title>Soft robotics and actuators</title>
        <p>Soft robotics has emerged as a transformative paradigm in robotics, offering mechanical compliance, adaptability, and safety, with relevance to minimally invasive surgery, wearable assistive devices, human-robot interaction, and unstructured environment exploration<sup>[<xref ref-type="bibr" rid="B289">289</xref>-<xref ref-type="bibr" rid="B291">291</xref>]</sup>. In contrast to rigid robots built from metals and hard polymers, soft robots are constructed from compliant materials capable of large deformation<sup>[<xref ref-type="bibr" rid="B292">292</xref>]</sup>. Their functionality relies on soft actuators that convert energy into controlled motion. Actuator performance depends on actuation mechanisms that govern responsiveness and operational constraints, and on structural design that determines motion complexity and controllability. This section reviews advances in soft actuators with emphasis on actuation principles and structural strategies enabling complex behaviors.</p>
        <sec id="sec4-3-1">
          <title>Actuation mechanisms</title>
          <p>Soft actuators can be categorized based on stimulus type, including electrostatic, electroosmotic, thermal, photoinduced, moisture-responsive, and ion-driven systems.</p>
          <p>Electrostatic actuation, exemplified by dielectric elastomer actuators (DEAs), relies on Maxwell stress generated by electric fields across dielectric layers between compliant electrodes<sup>[<xref ref-type="bibr" rid="B293">293</xref>]</sup>. Voltage application compresses the thickness and expands the in-plane area, enabling large strains<sup>[<xref ref-type="bibr" rid="B294">294</xref>]</sup>. These actuators offer high energy density, fast response, and silent operation, making them ideal for artificial muscles and dynamic morphing structures [<xref ref-type="fig" rid="fig10">Figure 10A</xref>]<sup>[<xref ref-type="bibr" rid="B295">295</xref>]</sup>, but often require high driving voltages, raising challenges for portability and safety, and may suffer from electrical breakdown and instability.</p>
          <fig id="fig10" position="float">
            <label>Figure 10</label>
            <caption>
              <p>Actuation mechanism and motion complexity and structural design. (A) DEA soft gripper grips a cube<sup>[<xref ref-type="bibr" rid="B295">295</xref>]</sup>. Copyright 2019, Elsevier; (B) Illustration of electro-osmotic actuation mechanism<sup>[<xref ref-type="bibr" rid="B296">296</xref>]</sup>. Copyright 2022, American Chemical Society; (C) Top: Actuation mechanism of LCE fiber; bottom: POM images of polydomain, monodomain, and isotropic states of LCE microfibers observed at two different angles with respect to the analyzer<sup>[<xref ref-type="bibr" rid="B300">300</xref>]</sup>. Copyright 2021, The American Association for the Advancement of Science; (D) Designed and manufactured single-finger, two-finger, and multi-finger hydrogel soft grippers for handling objects of different shapes (spheres, cylinders, and cubes), surfaces (flat, curved, and folded) and stiffness attributes (stainless steel, glass, plastic, and ultra-soft foods like tofu and egg yolks)<sup>[<xref ref-type="bibr" rid="B314">314</xref>]</sup>. Copyright 2026, Springer Nature; (E) The soft robot demonstrates the ability to lengthen into useful 3D structures<sup>[<xref ref-type="bibr" rid="B315">315</xref>]</sup>. Copyright 2017, The American Association for the Advancement of Science. DEA: Dielectric elastomer actuator; LCE: liquid crystal elastomer; POM: polarized optical microscopic.</p>
            </caption>
            <graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="ss6067.fig.10.jpg" />
          </fig>
          <p>Electroosmotic actuation exploits the movement of ions and solvent in porous or hydrogel matrices under electric fields [<xref ref-type="fig" rid="fig10">Figure 10B</xref>]<sup>[<xref ref-type="bibr" rid="B296">296</xref>]</sup>. It operates at low voltage and is suitable for micro-robot and microfluidic applications but can be limited by diffusion-constrained kinetics and modest force output. Thermally induced actuation relies on thermal expansion mismatch or phase transitions in materials such as shape memory polymers<sup>[<xref ref-type="bibr" rid="B297">297</xref>]</sup>, liquid crystal elastomers<sup>[<xref ref-type="bibr" rid="B298">298</xref>]</sup>, and bimorph composites<sup>[<xref ref-type="bibr" rid="B299">299</xref>]</sup>. Liquid crystal elastomers can contract anisotropically along mesogen alignment above phase transition temperatures, resembling muscle behavior [<xref ref-type="fig" rid="fig10">Figure 10C</xref>]<sup>[<xref ref-type="bibr" rid="B300">300</xref>]</sup>. Thermal approaches provide large stroke and force but can be slow and energy-intensive. Photothermal agents such as CNTs, graphene, and gold nanoparticles can enable remote and spatially controlled heating under light<sup>[<xref ref-type="bibr" rid="B301">301</xref>]</sup>. Photoinduced actuation enables wireless control by converting light into mechanical work. Direct systems use molecular photoswitches such as azobenzene through trans cis isomerization<sup>[<xref ref-type="bibr" rid="B302">302</xref>]</sup>, while indirect systems combine light absorbers with thermoresponsive matrices to achieve noncontact actuation<sup>[<xref ref-type="bibr" rid="B303">303</xref>]</sup>. These strategies are attractive for tether-free biomedical operation. Moisture-responsive actuation relies on differential swelling of hygroscopic materials such as cellulose under humidity gradients<sup>[<xref ref-type="bibr" rid="B304">304</xref>]</sup>. Biomimetic designs inspired by seed dispersal mechanisms can generate coiling, twisting, crawling, and other motions<sup>[<xref ref-type="bibr" rid="B305">305</xref>,<xref ref-type="bibr" rid="B306">306</xref>]</sup>. Such actuators can operate autonomously but may face slow response, limited reversibility in dry conditions, and durability concerns. Ion-driven actuation includes ionic polymer metal composites and conductive polymer actuators<sup>[<xref ref-type="bibr" rid="B307">307</xref>]</sup>. In ionic polymer metal composites, cation migration under low voltage bias causes hydration gradients and bending. These systems offer flexibility and bidirectional control<sup>[<xref ref-type="bibr" rid="B308">308</xref>]</sup> but may be limited by the solvent in electrolyte evaporation, electrode delamination, and finite lifetime.</p>
        </sec>
        <sec id="sec4-3-2">
          <title>Motion complexity and structural design</title>
          <p>Structural architecture strongly influences motion richness and controllability. Advances in fabrication, including multi-material three-dimensional printing, soft lithography, and kerygma and origami-inspired patterning, have enabled sophisticated geometries. Basic kinematic modes include bending, contraction, and elongation, and twisting and helical motion. Bending can be achieved through asymmetric material distribution or gradient crosslinking and is widely used in grippers and locomotive units<sup>[<xref ref-type="bibr" rid="B309">309</xref>]</sup>. Contractile actuators based on pneumatic networks, DEAs, or liquid crystal elastomers generate linear motion for propulsion<sup>[<xref ref-type="bibr" rid="B294">294</xref>,<xref ref-type="bibr" rid="B298">298</xref>,<xref ref-type="bibr" rid="B309">309</xref>]</sup>. Twisting and helical motion can be produced through chiral winding or anisotropic alignment, enabling rotary propulsion in swimming microrobots<sup>[<xref ref-type="bibr" rid="B310">310</xref>,<xref ref-type="bibr" rid="B311">311</xref>]</sup>. Programmable motion can be achieved by patterning actuation domains for sequential or selective activation. A dual stimuli responsive hydrogel combining light and humidity sensitivity demonstrated autonomous sequence execution through environmental feedback<sup>[<xref ref-type="bibr" rid="B312">312</xref>]</sup>. Electrode arrays integrated into DEA membranes can generate traveling wave deformation<sup>[<xref ref-type="bibr" rid="B313">313</xref>]</sup>. Biomimetic structural designs include octopus inspired grippers with tapered chambers for adaptive grasping [<xref ref-type="fig" rid="fig10">Figure 10D</xref>]<sup>[<xref ref-type="bibr" rid="B314">314</xref>]</sup> and vine tendril inspired elongating robots using localized swelling for tip extension [<xref ref-type="fig" rid="fig10">Figure 10E</xref>]<sup>[<xref ref-type="bibr" rid="B315">315</xref>]</sup>. Layered architectures integrating sensing layers, actuator layers, and reinforcement elements enable closed loop systems with proprioception and adaptive response<sup>[<xref ref-type="bibr" rid="B316">316</xref>]</sup>. Embedded sensors based on stretchable conductors such as liquid metals and conductive hydrogels can monitor strain and pressure for feedback control<sup>[<xref ref-type="bibr" rid="B317">317</xref>,<xref ref-type="bibr" rid="B318">318</xref>]</sup>. A soft gripper equipped with resistive strain sensors, for example, can adjust gripping force based on object compliance, preventing damage<sup>[<xref ref-type="bibr" rid="B319">319</xref>]</sup>.</p>
        </sec>
        <sec id="sec4-3-3">
          <title>Hydrogel actuators in varied environments</title>
          <p>One particularly promising application of hydrogel actuators is in relatively complex multi-arm robots or grippers that can operate in a variety of environments<sup>[<xref ref-type="bibr" rid="B320">320</xref>-<xref ref-type="bibr" rid="B322">322</xref>]</sup>. These hydrogel actuators can grasp objects when exposed to certain stimuli and release them. Such responsive actuators are now extensively used as intelligent components in robotic systems, flexible sensing devices, and mobile medical or surgical biopsy instruments, largely due to their ability to be programmed into specific shapes. Although this line of application is still emerging, soft grippers that can grip and release objects are among the most promising developments. For example, to expand the range of robotic hand applications, by incorporating GO and polypyrrole (PPy), Dong <italic>et al.</italic> developed a programmable, patterned GO/PPy dual-responsive hydrogel actuator that responded efficiently to both temperature and infrared irradiation<sup>[<xref ref-type="bibr" rid="B323">323</xref>]</sup>. Remarkably, the gripper can lift objects 38 times its own weight, mimicking the way an eagle catches its prey. This research offers an effective approach for developing hydrogel actuators and paves the way for potentials in intelligent actuator technology.</p>
          <p>A similar humidity-responsive hydrogel actuator was developed by Yao <italic>et al.</italic>, who employed an Eu<sup>3+</sup> ionic polyethyleneimine–acrylic acid copolymer (PEI-co-PAAC) in combination with poly(ethylene glycol) diacrylate (PEGDA)<sup>[<xref ref-type="bibr" rid="B324">324</xref>]</sup>. This actuator exhibited sensitivity to humidity and was capable of object detection and identification under ultraviolet light. Leveraging these properties, they designed a hexagonal hydrogel inspired by jellyfish camouflage, enabling the gripping and release of objects underwater. Zhao <italic>et al.</italic> reported another 4D printing innovation: an asymmetric bilayer-structured hydrogel actuator<sup>[<xref ref-type="bibr" rid="B325">325</xref>]</sup>. When gradually immersed in heated water, the actuator would catch and securely wrap a rubber block attached to a rope as immersion time increased. The wrapped object could then be moved by pulling the rope. Additionally, the actuator’s bending and releasing mechanism was adapted into bionic plant flower and hydrogel manipulator designs, making it easy to open/close or grasp/release target objects in response to thermal stimulation. Building on these strategies, researchers have recently developed even more advanced hydrogel actuators. These new designs function as intelligent fixtures, offering solutions that overcome the limitations of traditional fixtures, especially in challenging environments.</p>
          <p>Thermoresponsive hydrogels are highly promising for use in soft actuators because they can reversibly change shape in response to temperature fluctuations<sup>[<xref ref-type="bibr" rid="B326">326</xref>,<xref ref-type="bibr" rid="B327">327</xref>]</sup>. Recent advance includes the development of tough, rapidly responding thermoresponsive DN hydrogels engineered for soft actuators by Zhang <italic>et al.</italic> The resulting hydrogels exhibit excellent mechanical performance, with an ultimate compressive stress of approximately 8 MPa<sup>[<xref ref-type="bibr" rid="B328">328</xref>]</sup>. They also display rapid actuation, reaching about 30% linear contraction and 28% radial contraction within 2 min. Furthermore, tubular soft actuators can serve as fluidic temperature sensors, switching the direction of fluid flow due to temperature variations.</p>
        </sec>
        <sec id="sec4-3-4">
          <title>Intelligent control and feedback system</title>
          <p>The integration of intelligent control and feedback systems marks a major advance forward in the development of hydrogel-based soft robots. By embedding sensors and control units directly into the soft robotic structure, it becomes possible to continuously monitor key parameters such as fatigue, deformation, and actuation response in real time<sup>[<xref ref-type="bibr" rid="B329">329</xref>,<xref ref-type="bibr" rid="B330">330</xref>]</sup>. This closed-loop feedback allows for adaptive adjustments to actuator performance, ensuring reliable operation even in complex and changing environments. These smart systems not only improve the durability and functional reliability of hydrogel actuators but also broaden their potential for advanced applications in robotics, flexible sensing, and minimally invasive medical devices. Ultimately, combining responsive hydrogel materials with advanced control strategies sets the stage for the next generation of autonomous, adaptive, and multifunctional soft robotic systems<sup>[<xref ref-type="bibr" rid="B331">331</xref>,<xref ref-type="bibr" rid="B332">332</xref>]</sup>. For example, Huang <italic>et al.</italic> developed a foldable inductive sensor that could be integrated with an origami-inspired actuator<sup>[<xref ref-type="bibr" rid="B333">333</xref>]</sup>. With an increasing number of folds, the coil inductance decreased, leading to stable, sensitive, and highly repeatable performance, providing timely and reliable proprioceptive feedback for the gripper<sup>[<xref ref-type="bibr" rid="B333">333</xref>]</sup>. The final smart jellyfish design featured both buoyancy control and grasping capabilities under the water. In another example, Jin <italic>et al.</italic> developed a gas-driven flexible caterpillar robot equipped with advanced sensing capabilities<sup>[<xref ref-type="bibr" rid="B334">334</xref>]</sup>. The tactile sensors achieve a detection limit as low as 0.05 kPa along with an ultrafast response time of just 0.03 s. Meanwhile, the resistive strain sensors provide a sensitivity of 2.94 and can stretch up to 180%, allowing them to fully accommodate the robot’s body bending.</p>
          <p>Quadrupedal soft robots also demonstrate unique advantages, such as rapid crawling speeds and versatile movement patterns, making them well-suited for tasks like navigation, obstacle avoidance, and exploration. For example, Xu <italic>et al.</italic> introduced a multifunctional, controlled-buckling sensor for monitoring the locomotion of a quadruped soft robot<sup>[<xref ref-type="bibr" rid="B335">335</xref>]</sup>. The robot’s body was constructed to be independently actuated along the grid in two directions, enabling movement within the first quadrant of a two-dimensional surface. In another work, Tang <italic>et al.</italic> advanced the field further by using 3D printing to create magnetic hydrogel soft structures capable of complex shape changes<sup>[<xref ref-type="bibr" rid="B336">336</xref>]</sup>. By incorporating a hard-magnetic filler into the hydrogel matrix and employing nano-colloids to tune the rheology of the precursor, they were able to directly print intricate magnetic hydrogel shapes. These printed components were assembled into a 3D-printed magnetic hydrogel lotus, which is fully bloomed without a magnetic field. Under a uniform magnetic field, the lotus spreads flat; an upward field causes it to close completely, while a downward field induces opening.</p>
        </sec>
      </sec>
      <sec id="sec4-4">
        <title>From multimodal biosensing to AI-enabled health interfaces</title>
        <p>As hydrogel bioelectronics evolve from single-mode sensors to integrated health platforms, the key challenge is no longer only signal acquisition, but also the extraction of clinically meaningful information from complex, multimodal datasets. In this context, the convergence of hydrogel-based biosensing with wireless communication, microfluidic sampling, and AI-assisted data analysis is enabling a new generation of intelligent health interfaces capable of continuous monitoring, pattern recognition, and closed-loop intervention.</p>
        <sec id="sec4-4-1">
          <title>Wearable soft hydrogel biosensors</title>
          <p>Soft hydrogels are pivotal for wearable biosensors, offering skin-like compliance, high signal fidelity, and multimodal sensing capabilities by seamlessly integrating with biological tissues. In recent years, research on wearable soft hydrogel biosensors has shifted from merely enhancing mechanical performance to achieving more stable, precise, and intelligent health signal acquisition. Pan <italic>et al.</italic> developed a MXene-functionalized PEDOT:PSS conductive hydrogel for non-invasive sweat glucose monitoring, demonstrating high conductivity and stability enabled by the material’s tailored porous network [<xref ref-type="fig" rid="fig11">Figure 11A</xref>]<sup>[<xref ref-type="bibr" rid="B337">337</xref>]</sup>. Similarly, Zhao <italic>et al.</italic> engineered a dual-network hydrogel architecture with allylated hydroxyethyl cellulose with poly(3,4-ethylenedioxythiophene):poly(sodium-p-styrenesulfonate) and PAM, achieving remarkable pressure sensitivity and fast response for human motion tracking without external power<sup>[<xref ref-type="bibr" rid="B338">338</xref>]</sup>. Additionally, Wang <italic>et al.</italic> designed a rapid-polymerization hydrogel exhibiting autonomous self-healing and stable adhesion, allowing reliable operation under mechanical deformation and varying environmental conditions<sup>[<xref ref-type="bibr" rid="B339">339</xref>]</sup>. Furthermore, Shan <italic>et al.</italic> created an injectable hydrogel with integrated bacteria theranostic and motion monitoring functions, enabling real-time detection of joint movements and antibacterial protection for wound healing applications [<xref ref-type="fig" rid="fig11">Figure 11B</xref>]<sup>[<xref ref-type="bibr" rid="B340">340</xref>]</sup>. These advances highlight how soft hydrogels, through rational multiscale design, are evolving from passive conductors to intelligent, multifunctional interfaces for continuous health monitoring. Despite these advances, soft hydrogel-based wearable biosensors are hindered by inherent material vulnerabilities, including environmental instability and signal interference from calibration drift and biofouling<sup>[<xref ref-type="bibr" rid="B341">341</xref>,<xref ref-type="bibr" rid="B342">342</xref>]</sup>. These limitations collectively challenge their long-term reliability and commercial viability for continuous health monitoring.</p>
          <fig id="fig11" position="float">
            <label>Figure 11</label>
            <caption>
              <p>Representative design and applications of wearable hydrogel sensors for health monitoring. (A) demonstration of wearable sensor fabrication and sweat glucose detection<sup>[<xref ref-type="bibr" rid="B337">337</xref>]</sup>. Copyright 2024, Elsevier; (B) Structure, applications, and multi-functions of aminophenylboronic acid grafted SA (Alg-PBA)/PVA/GOH hydrogels<sup>[<xref ref-type="bibr" rid="B340">340</xref>]</sup>. Copyright 2024, Wiley-VCH; (C) The programmable microfluidic-assisted hydrogel patches<sup>[<xref ref-type="bibr" rid="B345">345</xref>]</sup>. Copyright 2024, Wiley-VCH; (D) A soft edible triboelectric hydrogel sensor for infant motion monitoring<sup>[<xref ref-type="bibr" rid="B346">346</xref>]</sup>. Copyright 2022, Wiley-VCH; (E) HOWS sensor featuring hydrogel optical waveguide with integrated wireless sensing and AI computing<sup>[<xref ref-type="bibr" rid="B347">347</xref>]</sup>. Copyright 2025, Wiley-VCH. SA: Sodium alginate; PBA: 3-aminophenylboronic acid; PVA: poly(vinyl alcohol); GOH: hydroxylated graphene; HOWS: hydrogel-based optical waveguide stretchable; PEDOT:PSS: poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate); GOx: glucose oxidase; PDMS: polydimethylsiloxane; PEIE: polyethyleneimine; LPA: lignin-polyacrylamide; PAAM: polyacrylamide acrylamide.</p>
            </caption>
            <graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="ss6067.fig.11.jpg" />
          </fig>
        </sec>
        <sec id="sec4-4-2">
          <title>Multimodal biosensing for comprehensive health data acquisition</title>
          <p>Multimodal biosensing integrates diverse physiological signals to provide comprehensive health monitoring, enabling real-time assessment of both biochemical and biophysical parameters for personalized healthcare. Soft hydrogels, with their intrinsic flexibility, biocompatibility, and tunable conductivity, serve as ideal platforms for developing wearable sensors that can conform to biological tissues and facilitate simultaneous data acquisition from multiple sources. For instance, Imani <italic>et al.</italic> developed a hybrid chemical-electrophysiological sensing system that concurrently monitors sweat lactate and electrocardiogram (ECG) signals, utilizing hydrogel-based interfaces to ensure skin compatibility and stable signal transmission during physical activities<sup>[<xref ref-type="bibr" rid="B343">343</xref>]</sup>. Lin <italic>et al.</italic> developed a non-invasive sweat glucose sensor that concurrently monitors ECG signals, demonstrating the integration of chemical and electrophysiological sensing in a single wearable platform. This hybrid system allows for the correlation of metabolic activity with cardiac function, providing a more holistic health assessment<sup>[<xref ref-type="bibr" rid="B344">344</xref>]</sup>. Furthermore, Liao <italic>et al.</italic> engineered a programmable microfluidic-assisted hydrogel patch with a silver-lignin-PAM composite for monitoring physiological signals like heart rate and pulse. This approach highlights the use of soft hydrogels in creating structured, multifunctional sensing interfaces through advanced fabrication techniques [<xref ref-type="fig" rid="fig11">Figure 11C</xref>]<sup>[<xref ref-type="bibr" rid="B345">345</xref>]</sup>. However, the broader deployment of soft hydrogel-based multimodal sensing systems is currently challenged by achieving environmental stability and integrated multimodal sensing for reliable clinical translation.</p>
        </sec>
        <sec id="sec4-4-3">
          <title>Data processing and AI-driven health insights</title>
          <p>Soft hydrogels serve as an ideal platform for AI-driven health monitoring by providing high-quality, multimodal physiological data through their biocompatible and conformable interfaces. The integration of deep learning algorithms with these sensors addresses challenges in processing complex, noisy data, enabling intelligent diagnosis and prediction. Guo <italic>et al.</italic> developed a deep learning-assisted triboelectric hydrogel sensor that achieved 100% recognition accuracy in monitoring infant movements by analyzing signals from various activities. This system enables real-time safety monitoring through wireless data transmission to a mobile device [<xref ref-type="fig" rid="fig11">Figure 11D</xref>]<sup>[<xref ref-type="bibr" rid="B346">346</xref>]</sup>. Li <italic>et al.</italic> engineered a hydrogel-based optical waveguide stretchable sensor integrated with a convolutional neural network to differentiate between normal and abnormal gait patterns for remote patient monitoring. This smart tele-healthcare system facilitates multimodal human-machine interaction, serving as a communication tool for patients with speech impairments [<xref ref-type="fig" rid="fig11">Figure 11E</xref>]<sup>[<xref ref-type="bibr" rid="B347">347</xref>]</sup>. However, a key limitation in current systems is the need for extensive, individualized data pre-training to overcome signal variability and achieve robust model generalization for reliable clinical insights.</p>
        </sec>
      </sec>
    </sec>
    <sec id="sec5">
      <title>OUTLOOK AND FUTURE OPPORTUNITIES</title>
      <p>Recent advances in soft yet robust hydrogels have opened new horizons for bio-integrated devices. To move beyond laboratory prototypes toward clinical translation and commercial adoption, future research must not only address reliability and stability but also explore transformative opportunities at the interface of materials science, engineering, and data intelligence.</p>
      <p>Toward predictive reliability: Future studies should integrate accelerated aging models with <italic>in-situ</italic> monitoring to quantitatively predict hydrogel device lifespan. Coupling fatigue mechanics with multi-scale imaging (e.g., synchrotron X-ray tomography, cryo-EM) will reveal crack initiation and conductive network degradation in real time. Such mechanistic insights can establish predictive design rules for long-term operation under physiological stress.</p>
      <p>Toward adaptive biointerfaces: Next-generation hydrogel interfaces should actively respond to biological cues rather than passively endure them. Smart surfaces capable of modulating immune reactions, releasing therapeutic agents, or dynamically adjusting adhesion will transform device–tissue integration. Incorporating bioinspired architectures (e.g., hierarchical porosity, anisotropic modulus gradients) can minimize fibrous capsule formation and achieve “invisible” integration.</p>
      <p>Toward multimodal intelligence: Hydrogel platforms are poised to evolve into multifunctional systems that combine sensing, stimulation, and therapeutic delivery. Embedding machine learning into signal processing will allow cross-validation of diverse physiological inputs, advancing toward closed-loop diagnostic and therapeutic frameworks. Beyond ECG or EMG, multimodal hydrogel arrays could integrate biochemical sensing of metabolites, enabling personalized monitoring at the molecular level.</p>
      <p>Toward scalable and sustainable translation: Commercialization requires convergence of scalable manufacturing, regulatory alignment, and sustainability. Roll-to-roll and 3D printing can reduce costs, while biodegradable polymers and circular design strategies will minimize environmental impact. AI-driven inverse design of hydrogel formulations, informed by quantitative composition–structure–property databases, will accelerate material discovery. Green manufacturing processes and modular device architectures will further establish a closed-loop material cycle, ensuring both clinical relevance and ecological responsibility.</p>
    </sec>
    <sec id="sec6">
      <title>CONCLUSIONS</title>
      <p>Strong and resilient soft hydrogels have become essential materials for developing flexible bio-integrated devices, thanks to their unique blend of mechanical strength, biocompatibility, and customizable physical properties. Their true value lies in the ability to design hydrogels at multiple scales, from molecular structures and network configurations to larger assemblies, which allows for simultaneous improvements in toughness, resistance to fatigue, and stability in various environments. These multi-scale mechanical design approaches are crucial for ensuring that hydrogels can reliably function and integrate with both electronic components and biological tissues over the long term. Advanced fabrication and scalable manufacturing techniques, such as high-resolution 3D printing, microfabrication, and advanced interface packaging, make it possible to precisely control hydrogel characteristics and seamlessly incorporate them into complex device systems. These breakthroughs have driven major advancements in areas like wearable electronics, e-skin, soft robotics, and multimodal biosensors, where hydrogels play a key role in connecting materials engineering with biomedical applications.</p>
      <p>Looking ahead, the field is on the verge of major breakthroughs fueled by trends like AI-driven material design, the creation of smart and adaptive interfaces, and the push for sustainable, scalable commercialization. These directions not only promise to speed up the discovery of next-generation hydrogel materials with exceptional performance, but also tackle key challenges related to clinical application and environmental sustainability. By combining data-driven design with cutting-edge fabrication and thorough <italic>in vivo</italic> testing, we aim to develop robust hydrogel platforms that can become clinically practical and environmentally friendly solutions for precision medicine and continuous health monitoring. In summary, the ongoing progress in strong and tough hydrogels, driven by multi-scale design and innovative manufacturing, will be crucial for enabling flexible, reliable, and intelligent bio-integrated devices that shape the future of healthcare.</p>
      <p>Strong and resilient soft hydrogels have become key materials for flexible bio-integrated devices because they combine tissue-like softness, biocompatibility, and mechanically robust performance. Recent progress shows that multiscale design, from molecular networks to microstructures and device interfaces, is essential for improving toughness, fatigue resistance, and long-term stability under physiological conditions. In parallel, advances in fabrication and integration strategies have expanded the use of hydrogels in wearable electronics, e-skin, soft robotics, and biosensing systems.</p>
      <p>Looking forward, further progress will depend on the integration of AI-assisted material design, adaptive bio-interfaces, scalable manufacturing, and rigorous <italic>in vivo</italic> validation. These efforts are expected to accelerate the development of hydrogel systems that are not only high-performing and reliable, but also clinically practical and environmentally sustainable. Overall, continued innovation in robust soft hydrogels will play a central role in enabling the next generation of flexible and intelligent bio-integrated devices for precision medicine and continuous health monitoring.</p>
    </sec>
  </body>
  <back>
    <sec>
      <title>DECLARATIONS</title>
      <sec>
        <title>Authors’ contributions</title>
        <p>Conceptualization: Yang, K.; Liu, W.</p>
        <p>Writing: Yang, K; Yang, X.; Zhu, W.; Liang, X.</p>
        <p>Review and editing: Yang, K; Yang, X.; Zhu, W.; Lu, C.; Liang, X.</p>
        <p>Supervision: Yang, X.; Zhu, W.; Liang, X.</p>
        <p>Project assistance: Liu, W.; Yi, Z.</p>
        <p>All authors contributed to the editing and approved the final version of the manuscript.</p>
        <p>All authors have read and agreed to the published version.</p>
      </sec>
      <sec>
        <title>Availability of data and materials</title>
        <p>Not applicable.</p>
      </sec>
      <sec>
        <title>AI and AI-assisted tools statement</title>
        <p>During the preparation of this manuscript, OpenAI GPT-4.5 (accessed in December 2025) was used solely to assist with the generation and refinement of graphical elements for <xref ref-type="fig" rid="fig1">Figure 1</xref> based on author-provided concepts and prompts. The tool did not influence the scientific content, experimental design, data collection, data analysis, interpretation, or conclusions of the work. All authors take full responsibility for the accuracy, integrity, originality, and final content of the graphical abstract and the manuscript.</p>
      </sec>
      <sec>
        <title>Financial support and sponsorship</title>
        <p>This work was supported by the National Natural Science Foundation (52403174); InnoHK initiative of the Innovation and Technology Commission of the Hong Kong roomSpecial Administrative Region Government; Natural Science Foundation of Guangdong Province (2025A0505010014, 2020A1515110288, 2025A1515011154); Natural Science Foundation of Hunan Province (2023JJ40655, 2025JJ40038); Shenzhen Science and Technology Program (RCBS20210609103713046, JCYJ20250604191212016); Agricultural Science and Technology Innovation Program and Outstanding Young Talents Funding of the Chinese Academy of Agricultural Sciences (CAAS-ASTIP-IBFC); Postdoctoral Research Start-up Funds of Dapeng New District and Shenzhen City.</p>
      </sec>
      <sec>
        <title>Conflicts of interest</title>
        <p>All authors declared that there are no conflicts of interest.</p>
      </sec>
      <sec>
        <title>Ethical approval and consent to participate</title>
        <p>Not applicable.</p>
      </sec>
      <sec>
        <title>Consent for publication</title>
        <p>Not applicable.</p>
      </sec>
      <sec>
        <title>Copyright</title>
        <p>© The Author(s) 2026.</p>
      </sec>
    </sec>
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