Recent progress of biomaterials-based hydrogels for wearable electronics and health monitoring

Abstract

Soft bioelectronics integrated with biological tissues are reshaping the landscape of personalized medicine, health diagnostics, and human-machine interfaces, yet they are frequently bottlenecked by the mechanical and biocompatibility discrepancies of conventional rigid hardware. Biomaterials-based hydrogels, defined as hydrogel systems constructed from natural polysaccharide or protein macromolecules, featuring extracellular matrix-like compliance, well-documented biocompatibility in numerous prior biomaterial studies and abundant functional groups, have emerged as promising interfacial materials to bridge this mechanical and biological mismatch. This review comprehensively surveys the state-of-the-art developments in polysaccharide-based (alginate, chitosan, and cellulose) and protein-based (collagen, silk fibroin, and bovine serum albumin) hydrogel platforms. It also analyzes their internal structures, crosslinking network topologies, and approaches to mechanical property regulation. Additionally, the deployment of these engineered hydrogels in capturing high-purity electrophysiological signals (e.g., electroencephalograms (EEG), electrocardiograms (ECG), and electromyograms (EMG)), as well as conducting respiratory monitoring and motion monitoring, is systematically evaluated. This review highlights critical structure-property trade-offs: reconciling mechanical softness, conductivity, biocompatibility and environmental stability remains a major unsolved bottleneck. In closing, the review concludes major contemporary challenges and future research routes for robust long-term wearable and implantable bioelectronics, to motivate original material designs of advanced soft biointerfaces for both wearable epidermal and implantable bioelectronic scenarios.

1 Introduction

The rapid development of artificial intelligence and the internet of things is driving profound transformations in biomedical engineering and intelligent human-machine interaction (Zhao Y. et al., 2025; Bai C. et al., 2026; Kong et al., 2026; Li W. et al., 2026; Song et al., 2026; Zhang et al., 2026). Driven by growing requirements for personalized medical treatment, early disease diagnosis, postoperative rehabilitation monitoring and intelligent human-machine interfaces, flexible wearable and implantable bioelectronics exhibit tremendous application potential in numerous fields (Chang et al., 2023; Hou et al., 2024; Niu et al., 2025; Li et al., 2026a). Unlike conventional rigid medical instruments that often cause user discomfort and severe motion artifacts, next-generation soft bioelectronics can establish potentially reliable, seamless tissue-device interfaces (Zhong et al., 2025; Zhu P. et al., 2026). These advanced systems dynamically fit the contours of the human body, enabling continuous and inconspicuous health monitoring while allowing free natural movement. To this end, researchers have developed various flexible sensing platforms capable of real-time acquisition of human electrophysiological and physiological signals (Chen et al., 2022; Li S. et al., 2025; Zhu Z. et al., 2026). These platforms enable the continuous monitoring of respiration, ECG, EEG, EMG, and body movements (Xu et al., 2026). Nevertheless, the mechanical adaptability, electrical stability, and biocompatibility at the human-device interface must meet exceptionally rigorous standards, as necessitated by these state-of-the-art applications. Consequently, developing novel bio-soft interface materials that combine superior mechanical performance with potentially reliable electrical conductivity has emerged as a central research focus in this field (Zhang et al., 2020; Ma et al., 2024).

To overcome the limitations of traditional bioelectronic devices regarding mechanical matching, biocompatibility, and long-term stability, novel hydrogel systems based on natural biomaterials have emerged as a research hotspot (Mao et al., 2017; Xu et al., 2023a; Farooq et al., 2025; Jeong et al., 2025; Zhu et al., 2025; Li X. et al., 2026). The three-dimensional soft networks resembling the extracellular matrix, combined with well-documented biocompatibility, render biomaterials-based hydrogels promising candidates for interfacing rigid electronics with soft biological tissues (Seliktar, 2012; Zhang and Khademhosseini, 2017; Zhang et al., 2020; Liu D. et al., 2023; Feng et al., 2024; Zhu and Fu, 2025). Natural macromolecular chains inherently possess abundant active functional groups, such as hydroxyl (-OH), amino (-NH2), and carboxyl (-COOH) groups (Gu et al., 2026; Yuan et al., 2026). These active sites not only enable the construction of physical/chemical cross-linked networks through hydrogen bonds, dynamic covalent bonds, and metal-ion coordination, but also serve as anchors for integrating conductive nanomaterials (including carbon nanotubes, graphene, MXene, metal nanowires, and liquid metals), conductive polymers, and bioactive agents (Xu et al., 2023b; Zhang et al., 2023; Htwe et al., 2026; Tang et al., 2026). Conductive hydrogels denote hydrogel systems that realize electrical signal transduction via electronic or ionic conductive pathways. Through molecular design and micro-network reconstruction strategies, biomaterials-based hydrogels can synergistically achieve reported favorable mechanical toughness, anti-freezing and water-retention properties, tissue adhesiveness, self-healing capability, and electrical conductivity, thereby significantly expanding their application potential in complex bioelectronic scenarios (Yang M. et al., 2022; Ferrante and Gonzalez, 2026; Ji Z. et al., 2026; Panda et al., 2026).

This review offers a systematic synthesis of recent progress in biomaterials-based hydrogels for flexible bioelectronics and human-machine interfacing, specifically as applied to wearable and implantable bioelectronic platforms (Zhu et al., 2022). Notably, ionogels refer to gel matrices where ionic liquids serve as the continuous phase; they are distinct from water-rich biomaterials-based hydrogels and should not be treated as interchangeable material categories. As depicted in Figure 1, we first delineate the molecular architectures, cross-linked network engineering, and mechanical-functional enhancement paradigms of protein-based (collagen, silk fibroin, and bovine serum albumin) and polysaccharide-based (alginate, chitosan, and cellulose) hydrogel platforms. Subsequently, their use in high-fidelity electrophysiological signal acquisition (EEG, ECG, and EMG) and real-time biomechanical monitoring (respiration and motion) is summarized, covering both wearable epidermal and implantable bioelectronic applications. Ultimately, perspectives are projected toward long-term bio-integration, all-weather wearability, and environmentally sustainable electronics. Consequently, these projections furnish a design framework for next-generation soft bio-interfaces. Many existing reviews treat material chemistry and device applications separately; this review bridges hydrogel structural design and healthcare-monitoring scenarios to fill this knowledge gap.

FIGURE 1

2 Classification of biomaterials-based hydrogels

2.1 Polysaccharide-based hydrogels

2.1.1 Alginate

Alginate, a polysaccharide polymer extracted from natural brown algae, has been widely utilized in tissue engineering and drug delivery owing to its good biocompatibility and mild ionic cross-linking properties (Ben Salem et al., 2025; Kurl et al., 2025; Li et al., 2026b; Wang et al., 2026). However, traditionally ionically cross-linked alginate hydrogels are constrained by several inherent limitations, including low mechanical strength, high brittleness, and limited functionality (Yan Z. et al., 2025; Zheng J. et al., 2025). These shortcomings hinder their ability to meet the demands of long-term application in complex physiological environments.

In recent years, researchers have proposed a series of structural design and network reconstruction strategies to address the aforementioned bottlenecks. To prevent gel shrinkage and improve mechanical properties, Ma et al. developed a novel LipoGel composite hydrogel (Figure 2a) (Ma T. et al., 2026). This material was created by blending sodium alginate solution with a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine lipid dispersion, followed by temperature-controlled concentration and ionic cross-linking upon CaCl2 addition. Compared to conventional sodium alginate hydrogels that suffer from obvious shrinkage and uneven light transmission after cross-linking, the optimized LipoGel was flat, transparent, and free from shrinkage deformation (Figure 2b). Furthermore, the introduction of dynamic covalent bonds endows alginate hydrogels with smart stimulus-responsive properties. Wang et al. successfully constructed a dynamically cross-linked composite hydrogel (Cat-SeCD@Gel) by employing polyphenol-functionalized selenium-doped carbon dots as multifunctional cross-linkers combined with phenylboronic acid-grafted sodium alginate (Figure 2c) (Wang et al., 2026). Owing to the specific responsiveness of phenylboronic acid moieties to the bacterial microenvironment, this system activates the catalytic activity of nanozymes to generate reactive oxygen species, thereby eradicating drug-resistant bacteria. Concurrently, the intrinsic chelating ability of the alginate backbone facilitates biofilm clearance, and this smart hydrogel integrating antibacterial, antioxidant, and osteoinductive properties offers new insights for osteomyelitis therapy. To meet the application demands under harsh mechanical conditions, a reconstruction strategy involving anisotropic drying, rehydration, and multivalent metal ion exchange was proposed by Ji et al. (2022). Following anisotropic drying shrinkage on a substrate, the pre-gel was rehydrated and secondarily cross-linked in a calcium ion solution, forming a reconstructed hydrogel with a dense, interconnected network (Figure 2d). Upon drying, the hydrogel contracted into a dense dry film, which subsequently regained water and swelled back into an intact hydrogel upon immersion in CaCl2 solution (Figure 2e). The hydrogel stably suspended a 2 kg weight without fracturing (Figure 2f), and the formed bulk hydrogel presented a regular morphology and structural integrity (Figure 2g). As shown in Table 1, Ca-Alg/D/Ca-Fe exhibited an ultra-high tensile strength of 57 MPa and a tensile modulus of 1290 MPa, far exceeding conventional Ca-alginate hydrogels. Nevertheless, its relatively low fracture strain of approximately 60% imposes limitations for wearable bioelectronic scenarios requiring large-deformation motion. In conclusion, alginate hydrogels have overcome the inherent limitations of conventional systems-namely, poor mechanical robustness and limited functionality. This has been achieved through various modification strategies, including lipid hybridization, dynamic covalent cross-linking, and anisotropic network reconstruction. As a result, these hydrogels have been endowed with reported favorable mechanical toughness, smart responsiveness, and multifunctional integration potential.

FIGURE 2

2.1.2 Chitosan

Chitosan, a natural polysaccharide featuring intrinsic antibacterial activity and well-documented biocompatibility in multiple biomaterial investigations, has attracted substantial attention in wound healing and bioelectronic interfaces (Chen J. et al., 2025; He et al., 2025; Ren M. et al., 2025; Yıldırım et al., 2025; Lu et al., 2026). However, the precise synergistic regulation of microstructure and macroscopic performance-along with the simultaneous impartation of specific functionalities-remains a pivotal challenge in the field.

Faced with the above obstacles, numerous innovative tactics involving molecular configuration design, microstructural modulation and state-of-the-art fabrication methods have been developed by researchers (Xia et al., 2025). To achieve synergistic optimization of mechanical performance and electrical conductivity under dynamic conditions, a composite hydrogel ink (CMAL) was engineered by Li et al. using methacrylated carboxymethyl chitosan (CMA) and synthetic Laponite nanoclay (LAP) (Figure 3a) (Li H. et al., 2025). In this system, strong electrostatic interactions and hydrogen bonding synergized between CMA and LAP to construct a robust, rapidly reversible physically cross‑linked network. This unique rheological behavior endowed the ink with reported favorable shear-thinning properties, ensuring smooth extrusion (Figure 3b). Meanwhile, rapid modulus recovery post-deposition adequately supported the fabrication of complex overhanging structures such as “Y”-shaped scaffolds (Figure 3c), thereby achieving high-precision, support-free 3D printing. To address the inherent challenge of fabricating continuous, ordered pores in conventional chitosan-based (CS-based) porous materials, Sun et al. derived inspiration from the ion-filtering functionality of plant stems (Sun et al., 2025). They dissolved CS in acetic acid solution and incorporated copper chloride to prepare a CS-Cu precursor. This precursor was then mold-cast and subjected to liquid nitrogen freeze-casting, followed by sequential ethanol regeneration and solvent exchange with water to yield a chitosan-copper (Ch-Cu) thermoelectric hydrogel (Figure 3d). During freeze-casting, directional ice crystal growth caused chitosan molecules to accumulate within the ice grain boundaries, progressively generating aligned, interconnected pore channels (Figure 3e). This biomimetic anisotropic structure not only provided low-resistance vertical pathways for ion transport, but also significantly boosted thermodiffusion entropy via spatial confinement. Driven by a temperature gradient, hydrated copper and chloride ions exhibited efficient directional migration (Figure 3f). This migration imparted superior negative thermoelectric performance to the material, thereby providing a potentially viable design framework for exploring the microstructural engineering of flexible thermoelectric hydrogels. As shown in Table 1, the Ch-Cu hydrogel delivers prominent ionic thermoelectric performance, yet relevant tensile mechanical data are not reported in the original literature, which constrains its evaluation for skin-worn scenarios.

FIGURE 3

2.1.3 Cellulose

Cellulose, owing to its high abundance, biodegradability, and rich hydroxyl functional groups, is regarded as an ideal raw material for constructing high-performance hydrogel electrolytes (Das et al., 2025; Dey et al., 2025; Xu Q. et al., 2025; Bai Y. et al., 2026). However, conventional cellulose-based systems have long been confronted with a trade-off between mechanical strength and ionic conductivity, which severely hampers their practical application in flexible wearable electronics (Feng et al., 2025; Ren C. et al., 2025; Brattelli and Gentile, 2026).

To overcome the aforementioned challenges, extensive studies have been devoted to the introduction of molecular network synergistic regulation and multiple cross-linking strategies. Addressing the bottlenecks of traditional cellulose hydrogel electrolytes, such as weak mechanical performance and poor processability that fail to satisfy the requirements of flexible zinc-ion batteries, Yang et al. constructed a dual-crosslinked cellulose hydrogel (DCH) electrolyte immersed in zinc sulfate solution (termed DCH-S) (Yang et al., 2026). This construction was inspired by the anion-reinforced effect. In this system, sulfate anions formed anion-hydrogen bonds with cellulose hydroxyl groups, thereby constructing a dense cross-linked network while expelling free water. This network concurrently provided continuous transport pathways for zinc ion migration (Figure 4a). Owing to the synergistic reinforcement of dense intermolecular hydrogen bonds and chemical cross-linking sites among cellulose chains, a mechanically robust and structurally stable three-dimensional network was established in this system. This structural design endows the hydrogel with reported favorable optical transparency (Figure 4b). Furthermore, it imparts superior processability, enabling the precise fabrication of intricate geometric shapes such as snowflakes and lotuses (Figure 4c). Furthermore, the hydrogel exhibited robust mechanical integrity, capable of stably supporting a 1 kg load and successfully lifting a 2 kg weight (Figures 4d,e), which substantiates the significant enhancement in mechanical properties. To address the issues of stress concentration and irreversible fracture caused by the modulus mismatch between rigid and flexible networks, Yin et al. designed a polyvinyl alcohol/cellulose nanofiber/tannic acid (PVA/CNF/TA) double-network hydrogel (Figure 4f) (Yin et al., 2026). This structural design effectively mitigates stress concentration and prevents irreversible fracture. In this architecture, Fe³⁺-crosslinked CNFs establish a rigid framework, whereas the incorporation of TA effectively reduces the modulus of the CNF network, achieving mechanical compatibility with the soft PVA phase (Jiao et al., 2024). Concurrently, the addition of TA significantly enhances non-covalent interfacial interactions between the two networks. The modified cellulose-based hydrogel strip could withstand large tensile deformations while maintaining its structural integrity after 360° twisting (Figure 4g). As shown in Table 1, the cellulose-based PVA/CNF/TA hydrogel demonstrated high stretchability (1000% ± 20%) and tensile strength (39.7 ± 1.7 MPa) with a moderate modulus of 10.0 ± 0.5 MPa, rendering it promising for large-strain flexible sensors. Consequently, it is positioned as a promising candidate for robust biomedical and flexible wearable sensors.

FIGURE 4

2.2 Protein-based hydrogels

2.2.1 Collagen

Collagen, as a natural structural protein, has been widely applied in tissue repair and regenerative medicine owing to its unique triple-helical conformation, low immunogenicity, and well-documented cytocompatibility across numerous biological studies (Arif et al., 2025; Lei et al., 2025; Yang et al., 2025). However, conventional collagen-based hydrogels are typically plagued by poor mechanical properties, which hinders their ability to maintain long-term stability within dynamic physiological environments (Sun et al., 2026).

Recent advances have witnessed abundant breakthroughs toward enhancing mechanical performance and functional integration within collagen composite hydrogels (She et al., 2025). To address the severe oxidative stress, high infection susceptibility, and insufficient mechanical and antibacterial properties of traditional fish-skin collagen hydrogels in diabetic wound treatment, a multifunctional hydrogel was fabricated by Geng et al. using fish-skin-derived collagen as the matrix (Geng et al., 2025). Into this matrix, a protocatechualdehyde-iron (III) complex chelate (PCA@Fe) — formed via metal-ligand coordination between PCA and ferric ions (Fe³⁺) — was incorporated, while dynamic Schiff-base cross-links formed between PCA and collagen amino groups (Figure 5a). This hydrogel not only significantly enhanced the thermal stability and mechanical strength of collagen, but also exhibited reported favorable macroscopic flexibility and bendability (Figure 5b). Additionally, Shen et al. engineered an injectable collagen-oxidized pullulan hydrogel loaded with penicillin G-copper (II) (termed CGO@Pg-Cu(II)) to address the limitations of existing pancreatic fistula sealants (Shen M. et al., 2025). These limitations include excessively rapid degradation, a lack of unilateral tissue adhesion, and the inability to balance profibrotic and antibacterial functions. The hydrogel was created by combining glycidyl methacrylate-grafted recombinant collagen (CF-GMA, derived from CF-1552) with oxidized pullulan (OP), alongside the incorporation of penicillin G-copper (II) infinite coordination polymer nanomedicines (Pg-Cu(II) ICPs) (Figure 5c). Upon UV irradiation, this hydrogel achieved firm adhesion and effective sealing at the pancreatic fistula site (Figure 5d), forming a stable physical barrier at the tissue interface (Figure 5e). Meanwhile, its non-contacting surface possessed anti-adhesion properties, preventing pathological adhesions with surrounding organs such as the liver and spleen. To overcome the limitations of traditional conductive collagen materials-namely limited stretchability and vulnerable conductive pathways under large deformations-Pei et al. developed a collagen ionic hydrogel (Pei et al., 2026). This hydrogel, utilizing collagen aggregate films as the matrix and introducing ionic components (Figure 5f), achieves a fracture strain of 560%, resilience of 97.36% and ionic conductivity of 0.56 S m^-1. It should be noted that such collagen-based ionogels employ ionic components and differ from conventional water-containing biomaterials-based hydrogels. By utilizing NaBr to induce a structural transition in collagen from long-range order to entropy-driven disorder while preserving the triple-helical conformation, a collagen ionogel was obtained with high tensile strain at break, reported favorable elasticity, and stable ionic conductivity (Figure 5g). Consequently, this material opens a new pathway for the design of biocompatible materials for next-generation wearable sensors and soft robotics (Gao et al., 2025). As shown in Table 1, CAF-NaBr reaches a fracture strain of 560% with stable ionic conductivity; nevertheless, its anti-dehydration performance for long-term on-skin use needs further improvement.

FIGURE 5

2.2.2 Silk fibroin

Silk fibroin, a natural macromolecular protein derived from silkworms, has attracted substantial attention in tissue engineering and flexible wearable electronics owing to its well-documented biocompatibility, tunable degradation rate, and reported favorable mechanical toughness (Gao et al., 2024; Sun et al., 2024; Wang et al., 2025a). However, unmodified pure silk fibroin hydrogels are generally constrained by inherent limitations, including high mechanical brittleness, lack of conductive pathways, and limited functionality, which hamper their further application in wearable sensing (Lin et al., 2024).

To enhance the osteogenic activity of silk fibroin (SF) hydrogels and mitigate their mechanical brittleness, Li et al. designed a growth-factor-free nanoscale-engineered silk fibroin (NESF) hydrogel (Figure 6a) (Ji Z. et al., 2026). By precisely regulating the length of SF nanofibers via sonication, more acidic groups were exposed and the surface negative charge was increased, effectively addressing the non-uniform deposition of silk fibroin fibers (Figure 6b). The resulting NESF hydrogel appeared macroscopically as a homogeneous, translucent white solid block (Figure 6c). Conventional silk fibroin gels suffer from several limitations, such as the difficulty of fabricating complex multilayered architectures and the reliance on potentially cytotoxic cross-linkers. To overcome these challenges, Och et al. injected a silk fibroin solution containing a ruthenium/sodium persulfate (Ru/SPS) photoinitiator system into molds (Och et al., 2026). This mixture was then subjected to directional freezing to induce aligned ice crystal growth, yielding frozen preforms. Subsequently, visible-light photocross-linking was applied to fix the polymer network. Finally, freeze-drying was carried out to remove the ice crystals, successfully yielding cryogels with oriented porous channels (Figure 6d). In contrast to conventional hydrogels, this cryogel exhibited a stable three-dimensional architecture that was capable of recovering its original shape after compression, whereas traditional silk fibroin hydrogels underwent irreversible damage and structural collapse upon compression (Figure 6e). Furthermore, to broaden the applications of silk fibroin hydrogels in bioelectronics and flexible sensing, Yan et al. leveraged the rich secondary structures of silk fibroin to construct a highly stable conductive hydrogel containing dense (Yan Y. et al., 2025), reversible multiple hydrogen bonds by combining silk fibroin with polyacrylamide (PAAm) and choline chloride (Figure 6f). After being cut apart, this hydrogel achieves self-repair within 1 minute and can withstand tensile strain as high as 300% (Figure 6g). Meanwhile, the hydrogel possesses favorable wet adhesion capacity toward rubber substrates and human skin (Figure 6h), which paves a potentially solid foundation for its deployment in flexible skin-mounted electronic devices. Thus, combining physical microstructural reconstruction with chemical functional cross-linking enables precise tailoring of the microscopic morphology and macroscopic performance of silk fibroin hydrogels. Consequently, this approach provides a promising route toward meeting the application demands of complex biological interfaces and flexible sensing.

FIGURE 6

2.2.3 Bovine serum albumin

Bovine serum albumin (BSA), owing to its favorable biocompatibility, facile modifiability, and abundant binding sites, has attracted substantial attention in constructing bio-functional hydrogels (Hong et al., 2022; Liu et al., 2024; Khan et al., 2025). However, single-component BSA hydrogels are generally constrained by inherent limitations, including low mechanical strength, poor degradation resistance, and limited functionality (Feng et al., 2022). These shortcomings hinder their ability to meet the application requirements of complex scenarios such as environmental responsiveness, smart adhesion, and drug delivery.

Recently, by modifying and reconstructing BSA, researchers have synthesized a series of multiply cross-linked composite hydrogels, effectively enhancing the mechanical strength, stimulus-responsiveness, and biological functions of BSA-based materials. To overcome the drawbacks including activity failure under low temperatures and poorly regulated adhesion behavior of BSA-based hydrogels, Chen and coworkers constructed a BSA/PAAm dual-network organohydrogel, as illustrated in Figure 7a (Chen J. et al., 2025). Organohydrogels represent hydrogel systems containing mixed water-organic solvent co-networks. The initial BSA/PAAm single-network organohydrogel enabled rapid, error-tolerant immediate attachment; upon thermal triggering, BSA underwent denaturation and unfolding to form a secondary network, thereby transforming into a double-network gel with ultra-strong adhesion. For free BSA solution, thermal treatment initiates protein denaturation and intermolecular crosslinking, accompanied by phase transition to solid hydrogel (Figure 7b). As shown in Table 1, BSA/PAAm DN-OHGs show ultra-high stretchability of 2200%, though it should be noted that PAAm is a synthetic polymer component in this organohydrogel system. In terms of functional assembly and targeted in vivo delivery, the self-assembly capability of BSA similarly played a pivotal role. Guo et al. utilized gallic acid (GA) and Cu²⁺ to self-assemble into poly (gallic acid)-copper (PGA-Cu) nanoparticles (Guo et al., 2025). Subsequently, these nanoparticles were conjugated with the targeting peptide SS08 to form PGA-Cu@SS08. This construct was then incorporated into a system comprising BSA, gelatin, and tris(2-carboxyethyl)phosphine (TCEP) to fabricate a composite hydrogel (Figure 7c). This BSA-based hydrogel not only possessed well-documented biocompatibility, but its stable physicochemical cross-linked network also effectively mitigated burst drug release, achieving long-term sustained release of active nanoparticles. Furthermore, conventional stimuli-responsive hydrogels have obvious deficiencies, including insufficient molding accuracy, single-function structures, and barriers to preparing complicated shape-morphing devices. To remedy these problems, Liu and coworkers synthesized a bovine serum albumin-poly (ethylene glycol) diacrylate (BSA-PEGDA) hydrogel capable of sequential morphological changes triggered by gastric environments (Figure 7d) (Liu et al., 2026b). In the gastric microenvironment, this hydrogel sequentially underwent acid-induced swelling, enzymatic degradation, and continuous morphological deformation, accomplishing a sequentially triggered structural transformation (Figure 7e). The mechanical stability of protein hydrogels can be greatly improved by taking advantage of the inherent properties of BSA, including thermal denaturation and unfolding, molecular self-assembly, and enzymatic degradability, combined with network hybridization and restructuring (Khan et al., 2025). These strategies work together to significantly enhance the overall mechanical performance. Meanwhile, this strategy offers innovative avenues to develop intelligent responsive wound dressings, drug delivery carriers and shape-morphing actuators (Shi et al., 2024).

FIGURE 7

3 Applications of biomaterials-based hydrogels in healthcare monitoring

3.1 Electrophysiological signals

3.1.1 Electroencephalogram

EEG can accurately reflect the electrical activity of cortical neurons, and its signal fidelity hinges on the contact quality at the electrode-skin interface (Yang L. et al., 2022; Zheng K. et al., 2025; Ji Z. et al., 2026; Liu et al., 2026c). Here it is worth noting that hydrogel electrodes fall into ionic-conductive and electronic-conductive categories, which differ in electrode polarization, impedance and resultant biosignal fidelity for EEG, ECG and EMG acquisition. Nevertheless, traditional commercial electrodes easily suffer from hydrogel dehydration, cutaneous irritation and motion-induced artifacts, which fails to meet the criteria of long-term dynamic physiological monitoring (Xu L. et al., 2025). In recent years, novel hydrogel epidermal electrodes-featuring low impedance, high conformal adaptability, and superior biocompatibility-have been established as an ideal platform for high-fidelity, noise-resistant EEG signal acquisition (Hu et al., 2024; Hong et al., 2026; Wang et al., 2025b).

Electrophysiological signals, such as EEG, hold significant value in human-machine interaction and health monitoring (Mirbakht et al., 2025; Zhang W. et al., 2025). However, weak epidermal signals are highly susceptible to motion artifacts, and conventional rigid electrodes suffer from insufficient user comfort, both of which compromise their suitability for prolonged dynamic monitoring. Inspired by these challenges, Zhang et al. engineered an ultrathin ionogel supported by a thermoplastic polyurethane (TPU) nanomesh (Zhang et al., 2025a), achieving high-precision, wireless continuous monitoring of multimodal physiological signals, including electrooculography (EOG), EEG, ECG, and EMG (Figure 8a). The sensor can stably record distinct uninterrupted EOG and EEG signals with high fidelity (Figure 8b). This ionic-conductive ultrathin nanonet-supported ionogel electrode achieves a skin-electrode interfacial impedance of approximately 10⁴ Ω at 100 Hz and can resolve characteristic EEG rhythms corresponding to different mental states. To address the bottlenecks of conventional brain-computer interface devices-namely, the discomfort caused by rigid electrodes and the consequent instability in long-term emotional EEG signal acquisition-Lan et al. developed an all-natural ionic biogel electrode (Lan et al., 2024). This electrode, composed of gelatin and sodium pyrrolidone carboxylic acid, was designed for long-term wireless EEG monitoring and sustained attention assessment. Centered around flexible circuit hardware adapted for head wear, the system wirelessly connected to terminal devices for signal transmission and visual display (Figure 8c). Signal analysis demonstrates obvious, distinguishable potential waveform characteristics under two states: relaxed eyes-closed status and eyes-open stimulation (Figure 8d). The flexible electrode conformally adhered to the skin (Figure 8e), enabling comfortable and stable signal acquisition. Moreover, under actual usage conditions, accumulated sweat and hair disturbance often impair the stable contact between electrodes and skin. This ionic-conductive GP biogel electrode can capture typical alpha-rhythm EEG signals during eyes-closed state and effectively mitigate blink-induced motion artifacts, delivering comparable spectral features to commercial EEG paste under parallel testing. To overcome sweat-induced adhesion failure, a novel all-physically cross-linked polyacrylic acid/lignin/konjac glucomannan (ALK) eutectogel electrode material was constructed by (Figure 8f) Liu T. et al., (2025). Under vigorous head movements, this electrode exhibited superior noise suppression compared to commercial counterparts, highlighting its dynamic anti-interference capability for daily long-term EEG monitoring and human-machine interaction scenarios.

FIGURE 8

3.1.2 Electrocardiogram

ECG is the surface potential projection generated by the synchronized depolarization and repolarization of cardiomyocytes initiated by the cardiac conduction system, essentially reflecting the spatiotemporally ordered integration of transmembrane ionic fluxes (Yan Y. et al., 2025; Zhang X. et al., 2025; He et al., 2026). These rhythmic bioelectrical signals on the millivolt level can precisely reflect cardiac rhythm, cardiac conduction performance and myocardial perfusion (Nan et al., 2025; Park et al., 2025; Zheng G. et al., 2026). They act as non-invasive, efficient and credible clinical evidence to diagnose cardiovascular diseases including arrhythmia, myocardial ischemia and myocardial infarction.

Traditional commercial gel electrodes face bottlenecks such as high skin interfacial impedance, severe motion artifact interference, and difficulties in achieving long-term high-fidelity signal acquisition (Tang et al., 2023; Rauf et al., 2024; Zhou et al., 2025). To overcome the aforementioned obstacles, inspired by the ion channels existing in biological neuronal synapses, Chen and coworkers prepared a biomimetic ionic hydrogel constructed with zwitterionic poly (sulfobetaine methacrylate) (pSBMA) and calcium alginate networks (Chen et al., 2026). This material was applied to record epicardial ECG signals of rats (Figure 9a). This hydrogel electrode exhibited robust adhesion to the wet surfaces of rat hearts and sciatic nerves, withstanding stretching without detachment (Figures 9b,c), indicative of reported favorable wet tissue-conformal stability. Quantitatively, this ionic-conductive BIH hydrogel electrode achieves an ECG signal SNR of 18.4 dB and a T/R amplitude ratio of 0.23, outperforming commercial Ag/AgCl gel electrodes (SNR = 16.9 dB, T/R = 0.14) under identical test conditions.Given the complex environment of dynamic, wet, and soft tissues like the pulsing heart, where traditional rigid electrodes fail to adapt to dynamic deformations and frequently suffer from interfacial detachment and contact instability, Wang et al. developed an implantable hydrogel bioelectronic device (Figure 9d) (Wang F. et al., 2024). The hydrogel electrode was implanted directly on the surface of the living heart through thoracotomy surgery (Figure 9e). Benefiting from reported favorable flexibility and adhesion performance, the electrode tightly attaches to the pulsating heart during operation, realizing long-term steady recording of cardiac electrophysiological signals (Figure 9f). Furthermore, to overcome the intrinsic limitations of high interfacial impedance and motion artifacts in epidermal electrodes, Wang et al. prepared a multifunctional bioadhesive hydrogel in another study (Wang F. et al., 2024). This hydrogel seamlessly conformed to human skin, thereby achieving long-term high-fidelity monitoring of epidermal electrophysiological signals including EEG, ECG, and EMG (Figure 9g). It is validated by continuous tracking data that ECG signals obtained with the sensor exhibit favorable stability during 12 h measurement (Figure 9h). For implantable scenarios, 3D-printed electronic-conductive PEDOT:PSS hydrogel electrodes achieve high-SNR (∼50 dB) epicardial ECG recording and stable signal acquisition over thousands of cardiac beating cycles. These stable signals deliver dependable conditions for full-time cardiac health monitoring. Consequently, hydrogel electrodes combining low interfacial impedance, robust bio-adhesion, and high conformal contact provide a solid guarantee for overcoming traditional electrode detachment and noise interference. This advancement paves the way for long-term, high-precision in vivo and in vitro ECG monitoring.

FIGURE 9

3.1.3 Electromyogram

EMG is a bioelectric signal formed by the spatiotemporal superposition of muscle fiber action potentials triggered by neural impulses, essentially reflecting the intensity, timing, and fatigue state of muscle contractions (Lu et al., 2024; Lai et al., 2025; Rescio et al., 2025; Xie et al., 2025; Zhang et al., 2025b). As a core indicator for evaluating neuromuscular function, EMG serves as a potentially reliable tool for revealing the biomechanical characteristics of muscle activity. Consequently, it provides crucial physiological evidence for the diagnosis of neuromuscular disorders, rehabilitation medicine assessment, and human-machine interaction control (Wu et al., 2026; Zhou et al., 2026).

Traditional commercial gel electrodes suffer from bottlenecks such as high contact impedance, low signal-to-noise ratio (SNR), and severe motion artifacts, making it difficult to satisfy the demands for long-term, high-quality multimodal epidermal electrophysiological signal acquisition (Zhang et al., 2025c; Bazyleva et al., 2026; Mohammadiazni et al., 2026). To tackle this problem, Chen and coworkers developed a biomimetic ionic hydrogel electrode featuring high electrical conductivity and low elastic modulus (Chen et al., 2026). Ionic hydrogels are a subclass of hydrogels, in which electrical conduction is dominated by ion transport within aqueous networks. This electrode permits synchronous collection of diverse physiological signals at different body positions, such as EEG, ECG and EMG signals (Figure 10a). This electrode accurately recorded EMG signals generated by various upper-limb movements, such as elbow flexion and grasping (Figure 10b). Meanwhile, under identical motion conditions, the BIH hydrogel electrode achieves an EMG SNR of 23.2 dB, compared with 17.1 dB for conventional commercial electrodes (Figure 10c), demonstrating its capability for acquiring superficial bioelectrical signals. To address the challenges of traditional conductive hydrogels, such as easy detachment during prolonged wear, large motion artifacts, and poor conductivity stability, Yan et al. developed a flexible conductive hydrogel electrode featuring controllable adhesion properties (Yan X. et al., 2025). Conformable to the chest and arm, this electrode enabled simultaneous acquisition of ECG and EMG signals during weight-bearing exercise, thereby supporting remote diagnosis via cloud transmission (Figure 10d). The electrode transitioned from a weakly adhesive state upon skin contact to a strongly adhesive state post-pressing or triggering, driven by increased contact area or enhanced interfacial interactions (Figure 10e). Comparative evaluations before and after sweaty exercise demonstrated that the EMG signals acquired by this hydrogel electrode remained intact and stable, indicative of reported favorable dynamic anti-interference performance (Figure 10f). Moreover, conventional rigid Ag/AgCl electrodes suffer from microscale interfacial voids between skin and electrodes; such defects lead to signal distortion in long-duration monitoring. To address these shortcomings, Yan and coworkers built a dual-electrode ionogel system for EMG signal verification (Yan et al., 2025). Compared to traditional rigid electrodes, the ionogel electrode achieved seamless conformal contact with the skin owing to its superior flexibility, effectively reducing contact impedance by eliminating interfacial air gaps and thereby ensuring long-term continuous electrophysiological signal collection (Figure 10g). Experimental measurements demonstrated that the EMG signals recorded during arm relaxation, extension, and fist-clenching exhibited higher amplitudes and more distinct features. Notably, stable recording performance was retained after 20 days of ambient storage (Figure 10h), substantially surpassing commercial electrodes in both longevity and signal fidelity.

FIGURE 10

3.2 Respiratory monitoring

Respiratory monitoring plays a crucial role in early disease diagnosis, post-operative critical care, and sleep disorder assessment by real-time acquisition of key parameters such as respiratory rate, amplitude, rhythm, and gas exchange (Hu et al., 2025; Peng et al., 2025; Shen M. et al., 2025; Wu et al., 2025; Guan et al., 2026). However, traditional respiratory monitoring devices generally rely on a single sensing mode, which hinders the decoupling of interference arising from multiple coupled stimuli, including temperature, humidity, and mechanical deformation (Zhao et al., 2026). Therefore, developing smart respiratory monitoring systems that integrate multi-parameter discrimination capabilities, long-term stability, and wearing comfort still awaits key breakthroughs in material and structural design (Yu et al., 2025; Zheng J. et al., 2025; Li et al., 2026c).

Minor airflow and humidity variations induced by oral, nasal and thoracoabdominal respiration are hard to be accurately measured via traditional sensors (Liu H. et al., 2023; Ni et al., 2024). Furthermore, external power sources serve as an indispensable power supply for most sensing apparatuses. To address this bottleneck, Zheng et al. fabricated a self-powered MXene/calcium alginate humidity-sensing film paired with Al/Cu electrodes to construct a bio-respiration monitoring device (Figure 11a) (Zheng Q. et al., 2025). Working independent of external power supplies, the device achieves sensitive responses to respiratory signals when mounted on the facial skin (Figures 11b,c). Experimental results demonstrated that the sensor clearly captured respiratory waveforms and effectively distinguished nasal breathing from oral breathing via characteristic differences in voltage amplitude and waveform profile (Figure 11d), thereby indicating its potential for respiratory pattern tracking (humidity-responsive ionic sensing), which is sensitive to exhaled moisture yet susceptible to ambient humidity fluctuations. Additionally, Liu et al. developed a multimodal hydrogel sensor (CH-GT, a double-cross-linked cellulose hydrogel modified with tannic acid and a glycerol-water system) constructed from tannic acid, a glycerol-water system, and double-cross-linked cellulose (Liu et al., 2022). This sensor was designed to address the susceptibility to monitoring errors in existing single-modal devices that rely on a single physiological parameter to infer breathing status. Attached to the chest, the sensor captured synchronized capacitance variations driven by chest expansion and contraction during inhalation and exhalation (capacitive transduction), suitable for recording mechanical chest-wall deformation but easily interfered by stray environmental capacitance. Based on waveform periodicity and peak height, it distinguished the frequency and depth of normal, rapid, and deep breathing patterns (Figure 11e). Furthermore, during abdominal capacitance monitoring, because abdominal excursions exceed chest movements, the capacitance peak values under equivalent breathing intensities were significantly higher than those from the chest. Moreover, during breath-holding, the capacitance maintained a steady baseline, with periodic fluctuations immediately resuming upon respiration recovery (Figure 11f). In summary, flexible hydrogel sensors possess reported favorable conformability, high sensitivity and favorable environmental tolerance (Yang M. et al., 2022). These merits allow the sensors to efficiently address the difficulty in accurate detection of faint respiratory airflow and bodily deformation. Consequently, they lay a potentially reliable foundation for noninvasive diagnosis and all-day smart monitoring of respiratory illnesses represented by sleep apnea. Notably, sensing metrics of hydrogel respiratory sensors differ due to varied test environments. The MXene-alginate humidity-sensitive hydrogel delivers fast response under humidity stimuli, while the dual-mode cellulose-based CH-GT hydrogel can separate airflow and chest-abdomen motion signals to reduce misreading risks. However, long-term cycling stability, baseline-drift data under real-human breathing conditions, and systematic benchmarking against commercial devices are still insufficient in existing reports.

FIGURE 11

3.3 Motion monitoring

Human motion monitoring provides crucial data support for rehabilitation evaluation, athletic training, and disease management by collecting key parameters such as joint angles, muscle activity, gait, and posture in real time (Duan et al., 2025; Li J. et al., 2025; Wang F. et al., 2025; Zhang et al., 2025d). Benefiting from high water content, tunable stiffness and skin-like soft conformability, hydrogel materials are able to closely adhere seamlessly to human epidermis. Motion artifacts are remarkably restrained, and high fidelity is maintained throughout signal measurement (Chen H. et al., 2025; Li et al., 2026d). With the introduction of conductive nanofillers or the fabrication of ion-conducting networks, hydrogels can convert various mechanical deformations such as bending and stretching into electrical signals (Li et al., 2023; Guo et al., 2026; Ji C. et al., 2026). Consequently, this capability allows for precise recognition and real-time feedback of full-range human motion states.

Traditional wearable biosignal sensing technologies face challenges with user irritation and discomfort caused by unwanted objects in constant direct contact with the skin (Almujally et al., 2025; Oh et al., 2025). To address this challenge, a fabric-based lamina emergent MXene-based electrode (FLEXER) was constructed by Lee et al. and assembled into a concealable wearable system for real-time electrophysiological monitoring (Figures 12a,b) (Lee et al., 2024). This sensor boasts a unique shape-morphing pneumatic structure. This electrode can smoothly retract to an inactive configuration to avoid persistent physical contact. Once activated, it enables stable, low-noise signal collection under various dynamic scenarios including standing, walking and driving (piezoresistive transduction), responding to mechanical contact pressure for on-demand signal acquisition. Furthermore, traditional approaches face a clinical dilemma in infected wound theranostics, where the independent operation of dressings and monitoring devices hinders the simultaneous achievement of wound antibacterial efficacy and limb rehabilitation tracking. To address this challenge, Shan et al. developed a multifunctional injectable conductive hydrogel (Shan et al., 2024). This hydrogel is adaptable to infected wounds on various anatomical sites, including limbs and the torso (Figure 12c). Repeated wrist flexion-extension tests demonstrated that the hydrogel sensor output stable, non-attenuating resistance signals, exhibiting reported favorable sensing repeatability (piezoresistive transduction), well-suited for quasi-static joint strain monitoring. (Figure 12d). Traditional hydrogel-based motion sensors confront prominent limitations: rapid water loss, drastic baseline drifting of detection signals, and inadequate adaptability to prolonged continuous service. To solve these challenges, Zhu and coworkers synthesized a breathable ultrathin film sensor composed of an electrospun TPU nanomesh-reinforced organohydrogel (Zhu C. et al., 2024). This system successfully supports the construction of a skin-attachable continuous motion monitoring system (Figure 12e). This anti-dehydration device enables real-time collection of relative resistance signals produced by knee flexion movements (piezoresistive transduction), whose long-term stability benefits from its anti-desiccation structural design. It precisely records motion features during all-day continuous stair ascent and descent and thoroughly eliminates the prominent baseline drift commonly observed in traditional hydrogel materials.

FIGURE 12

4 Summary and outlook

In summary, biomaterials-based hydrogels constructed from natural proteins (such as collagen, silk fibroin, and bovine serum albumin) and polysaccharides (such as alginate, chitosan, and cellulose) have emerged as essential soft interfacial materials for next-generation flexible bioelectronics and intelligent human-machine interfaces targeting both wearable epidermal and implantable healthcare scenarios (Bao et al., 2016; Amponsah et al., 2025; Banerjee et al., 2025; Dumitru et al., 2025; Li et al., 2026e). Possessing superior biocompatibility, soft mechanical behaviors analogous to the extracellular matrix, and ample reactive functional moieties, these natural macromolecular frameworks serve as a promising physiological linker (Carton et al., 2025; Curto et al., 2025). Accordingly, they effectively bridge the mechanical and biological gaps between rigid electronic devices and soft native tissues (Zhu P. et al., 2024). Through rational molecular network cross-linking, microstructural engineering, and the construction of tailored ionic/electronic conductive pathways, biomaterials-based hydrogels are successfully engineered. Consequently, they synergistically integrate high mechanical toughness, tissue-conformal adaptability, self-healing capability, environmental tolerance, and superior electrical conductivity. Accordingly, these multifunctional hydrogel substrates are reported to exhibit versatile performance across diverse biomedical fields (Khayal and Nami, 2025; Omidian and Dey Chowdhury, 2025; Jiang et al., 2026). They are capable of stably capturing high-fidelity electrophysiological signals (EEG, ECG, EMG) over long durations and achieving real-time multimodal biomechanical tracking of respiration and bodily kinematics (Singh et al., 2025; Liang et al., 2026). In this way, they provide a promising material framework for next-generation wearable health monitoring, implantable theranostic systems, and interactive soft robotics.

Despite significant progress achieved by biomaterials-based hydrogels in flexible bioelectronics and human-machine interactions, multiple key challenges remain to be addressed for clinical practical applications and round-the-clock, long-term wearable or implantable demands (Hosseini et al., 2025; Akter and Ramli, 2025; Li et al., 2026; Liu et al., 2026c). First of all, hydrogels are limited by unsatisfactory environmental stability and mechanical durability (Dong et al., 2025; Chen G. et al., 2025). Exposed to open surroundings, such materials tend to lose water and dry out. They are also susceptible to failure caused by freezing under low-temperature environments. Moreover, long-term repeated dynamic deformation and complicated body fluid environments may lead to fatigue rupture, interfacial detachment, as well as abnormal swelling or degradation of hydrogels (Lin and Hsu, 2025; Zhang W. et al., 2025). Second, the synergistic enhancement of mechanical performance, electrical conductivity, and biocompatibility remains difficult, and excessive introduction of cross-linkers or conductive fillers often comes at the expense of material compliance, transparency, or biocompatibility (Zhao W. et al., 2025; Tian et al., 2026; Yu and Adronov, 2026). Moreover, prominent mechanical and electrical mismatches exist during heterogeneous integration of soft hydrogel interfaces with stiff electronic chips and wireless transmission modules (Li and Chen, 2025; Wang Y. et al., 2025). Meanwhile, dynamic disturbances including motion artifacts and skin sweating drastically reduce the signal-to-noise ratio during bioelectrical signal collection. Finally, the fabrication process of high-performance hydrogels is sensitive to environmental factors, and scalable continuous processing technologies alongside unified standardized evaluation criteria are still lacking (Bai et al., 2025; Hu et al., 2025; Rahman et al., 2025; Wang and Yang, 2025). Inconsistent experimental conditions and divergent performance-metric definitions across literature impede direct cross-study comparison. For better reproducibility, future hydrogel-sensor reports are encouraged to clearly document major testing parameters when describing sensing performance. It should be emphasized that natural polymer origins cannot equate to full environmental sustainability. Various practical factors should be comprehensively weighed when assessing the overall eco-friendliness of these hydrogel systems. Nevertheless, considerable regulatory potential is exhibited by polysaccharide and protein-based bio-hydrogels, owing to their distinctive molecular architectures and functional characteristics. Importantly, biocompatibility cannot be directly extrapolated only from the natural polymer source. Composite hydrogels incorporated with nanofillers, metal-ion species and cross-linkers require dedicated biological evaluation, rather than assumptions merely based on raw-material origins. Reasonable selection of matrix raw materials, optimized design of network structures, and introduction of functional conductive fillers allow researchers to precisely regulate the mechanical characteristics, electrical conductivity and environmental adaptability of hydrogels. These strategies establish a solid material foundation for the applications of biomaterials-based hydrogels in next-generation epidermal electronics, wearable sensing systems, and intelligent human-machine interfaces. Taking natural polysaccharide- and protein-derived hydrogels as the main thread, this review distinguishes itself by jointly analyzing material-level network engineering and practical wearable health-monitoring scenarios, rather than separately discussing material chemistry or device applications. Future research priorities may focus on anti-dehydration and antifreeze strategies, fatigue-resistant network design, low-impedance biointerfaces, scalable manufacturing, standardized testing protocols, long-term human validation, as well as regulatory and clinical translation toward real-world bioelectronic deployment.

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