Two-Dimensional Materials for Biosensing: Emerging Bio-Converged Strategies for Wearable and Implantable Platforms

Abstract

The development of functional biosensors is rapidly advancing in response to the growing demand for personalized and continuous healthcare monitoring. Two-dimensional (2D) nanostructured materials have attracted significant attention for next-generation biosensors due to their exceptional physicochemical properties, including a high surface-to-volume ratio, excellent electrical conductivity, and mechanical flexibility. The integration of 2D materials with biological recognition elements offers synergistic improvements in sensitivity, stability, and overall sensor performance. These unique properties make 2D materials particularly well-suited for constructing wearable and implantable biosensors, which require conformal contact with soft tissues, mechanical adaptability to body movement, and reliable operation under physiological conditions. This review highlights recent advances in functionalized and composite 2D materials for wearable and implantable biosensing applications. We focus on key strategies in surface modification and hybrid nanostructure engineering aimed at optimizing performance in dynamic, body-integrated environments. Finally, we discuss current challenges and future directions for clinical translation, emphasizing the potential of 2D-material-based biosensors to drive progress in personalized and precision medicine.

1. Introduction

Two-dimensional (2D) nanomaterials are increasingly recognized not merely for their unique intrinsic physicochemical properties but also for their remarkable adaptability to biosensing applications through precise physicochemical customization at the atomic and molecular levels [1,2,3,4]. Unlike conventional bulk materials, 2D structures such as graphene, transition metal dichalcogenides (TMDCs), and MXenes can be rationally engineered to fulfill specific biosensing requirements, including enhanced sensitivity, selectivity, mechanical flexibility, and biocompatibility [5,6,7]. These combined characteristics have enabled the development of high-performance biosensors compatible with integration into advanced biomedical systems [1,4,5,6,7,8,9,10].

Recent advancements in the synthesis and functionalization of 2D materials, particularly graphene [11,12,13,14], TMDCs [15,16,17,18], and MXene [19], have substantially broadened their application potential (Figure 1). These materials have demonstrated improved sensitivity, selectivity, and stability in biosensors spanning electrochemical, optical, and field-effect transistor-based modalities [1,4,5,10]. Tailored surface modification strategies have further enhanced their biochemical specificity, allowing these nanomaterials to better adapt to complex biological environments [4,6,7,8,9].

However, despite these inherent advantages, pristine 2D nanomaterials often encounter significant limitations when applied directly in complex biological settings [20,21,22]. Challenges such as limited biocompatibility, instability under physiological conditions, and inadequate interface compatibility with biomolecules restrict their practical utility [23,24]. These issues largely stem from the native surfaces lacking sufficient chemical functionality to ensure stable and selective biomolecular recognition, often leading to signal drift, biofouling, and reduced sensor longevity in vivo.

To address these challenges, recent research has emphasized tailoring the physicochemical properties of 2D nanomaterials through surface functionalization, heteroatom doping, and interface engineering [25,26,27,28,29,30,31]. Such modifications enable precise control over sensitivity, selectivity, biocompatibility, and mechanical integration, thereby optimizing the materials’ performance in demanding biosensing environments [4,6,8]. For instance, grafting biocompatible polymers onto surfaces reduces non-specific adsorption, doping adjusts electronic and catalytic behavior to enhance responsiveness, and interface-specific functionalization improves the signal transduction and physiological stability essential for reliable operation in biofluids [24,32].

These advances have facilitated the integration of 2D nanomaterials into diverse biosensor platforms, including flexible epidermal patches, wearable electronic circuits, and implantable microneedle arrays, where device performance critically depends on finely tuned material–biointerface interactions [4,21]. No longer serving merely as passive substrates, 2D materials have evolved into actively tunable components adaptable across various diagnostic modalities and physiological environments [33,34].

While previous reviews have primarily focused on the fundamental sensing mechanisms and intrinsic physicochemical properties of 2D nanomaterials, this review highlights recent progress in customized design strategies specifically aimed at wearable and implantable biosensing applications, offering a distinct perspective. These platforms impose complex demands such as long-term biocompatibility, mechanical flexibility, and stable operation under dynamic physiological conditions that cannot be adequately met by unmodified materials alone. Consequently, recent efforts have concentrated on tailoring 2D nanomaterials via surface modifications, controlled electronic properties, and interface-specific functionalization to optimize performance within biological milieus. These technological advancements play a pivotal role in transforming 2D materials into highly precise and reliable biosensor platforms. This review comprehensively examines these application-driven customization strategies, analyzes integration examples in wearable and implantable biosensors, and underscores the critical need for clinical translation and practical implementation.

2. 2D Materials for the Biosensor Application

2D materials, characterized by their single or few atomic-layer thickness, have garnered significant attention due to their exceptional physicochemical properties [35,36,37]. Among them, graphene has emerged as a prototypical 2D material, exhibiting a high specific surface area, superior thermal conductivity, robust mechanical strength, half-integer quantum Hall effect, and ultrafast carrier mobility [38,39]. Inspired by these properties, a wide variety of 2D materials have been synthesized from their bulk counterparts, including graphitic carbon nitride (g-C₃N₄), MXenes, hexagonal boron nitride (h-BN), TMDCs, and black phosphorus (BP) [40,41] (Figure 2). These materials can be broadly categorized as metallic, semimetallic, semiconducting, superconducting, or insulating, depending on their crystal structure and chemical composition [42]. Owing to their planar morphology and tunable atomic configurations, 2D materials offer immense potential for property enhancement and functionalization through techniques such as surface modification, chemical doping, bandgap engineering, and thickness control. These approaches are often challenging to achieve in conventional bulk materials [43,44,45].

2.1. Graphene

Graphene, the archetypal 2D material, is composed of a single layer of sp²-hybridized carbon atoms arranged in a hexagonal lattice. Since its first isolation via mechanical exfoliation in 2004, graphene has become a focal point in nanomaterials research due to its exceptional intrinsic properties. Despite being only one atom thick, graphene exhibits remarkable electrical, thermal, mechanical, and optical characteristics. Electrically, it features ultra-high charge carrier mobility (up to ~200,000 cm²/V·s) and supports ballistic transport over submicron distances, which is attributed to its unique electronic structure [46,47,48,49]. Graphene behaves as a semimetal with a linear energy dispersion near the Dirac points, effectively mimicking massless Dirac fermions [50]. However, its zero bandgap poses a critical limitation for conventional digital logic applications, where a distinct on/off current ratio is essential. To overcome this, various bandgap engineering approaches have been investigated, including quantum confinement in graphene nanoribbons, chemical functionalization, and substrate-induced symmetry breaking [51]. Thermally, graphene possesses outstanding thermal conductivity (>3000 W/m·K), while mechanically, it is among the strongest known materials, with a Young’s modulus of approximately 1 TPa and a tensile strength around 130 GPa [49]. Additionally, its high flexibility and mechanical resilience make it suitable for applications in flexible electronics.

Graphene also demonstrates high optical transparency, absorbing only ~2.3% of incident visible light per layer, and possesses an extremely large specific surface area (~2630 m²/g) [52]. These attributes, combined with its tunable surface chemistry, render it a highly versatile platform for optoelectronic devices, chemical sensors, and energy storage systems. Its surface can be readily functionalized via covalent or non-covalent interactions, enabling integration into composite or hybrid structures with tailored functionalities [53]. Furthermore, graphene’s biocompatibility and ease of functionalization have opened avenues in the biomedical field, including applications in biosensing, bioimaging, and targeted drug delivery [54,55,56].

In summary, the extraordinary combination of graphene’s electronic, thermal, mechanical, and optical properties, along with its atomic thickness and chemical tunability, positions it as a transformative material with wide-ranging applications across nanoelectronics, flexible and wearable devices, energy systems, and biomedical technologies.

2.2. Transition Metal Dichalcogenides (TMDCs)

TMDCs represent a prominent class of 2D layered materials with the general chemical formula MX₂, where M denotes a transition metal element from groups IV, V, or VI (e.g., Ti, Zr, Hf, V, Nb, Ta, Mo, W, or Cr) and X represents a chalcogen atom (S, Se, or Te). TMDCs possess a characteristic trilayered structure, in which a single layer of transition metal atoms is sandwiched between two layers of chalcogen atoms. Each monolayer is stabilized by strong covalent bonds, whereas the stacking between adjacent layers is governed by weak van der Waals interactions. Depending on the coordination environment, TMDCs can crystallize in different polymorphs, notably the 1T (octahedral coordination) and 2H (trigonal prismatic coordination) phases, both of which critically influence their electronic and optical properties [57].

TMDCs are distinguished by their wide spectrum of electronic characteristics, ranging from metallic (e.g., VSe₂ and NbS₂), semimetallic (e.g., TiSe₂ and WTe₂), semiconducting (e.g., MoSe₂, MoS₂, WS₂, and WSe₂), to insulating (e.g., HfS₂) behaviors [58,59,60]. Among these semiconducting TMDCs, MoS₂ has been widely studied for its high current-on/off ratio in field-effect transistors (FETs), making it a leading candidate for nanoelectronic applications [61,62,63]. A distinctive characteristic of TMDCs is the transition from an indirect to a direct bandgap when reduced from bulk to monolayer form, which leads to a substantial enhancement in photoluminescence efficiency. For instance, while bulk MoS₂ possesses an indirect bandgap, its monolayer form exhibits a direct bandgap of approximately 1.8 eV [64,65,66].

Moreover, TMDCs such as MoS₂ and WSe₂ feature atomically thin surfaces free of dangling bonds, which enable the formation of nearly ideal Schottky junctions with minimal Fermi level pinning. This is an essential attribute for efficient charge carrier transport [67]. However, the performance of TMDC-based devices is highly sensitive to extrinsic factors such as grain boundaries, metal–semiconductor contact quality, and the nature of the underlying substrate, all of which significantly affect carrier mobility and device reliability [68,69,70,71]. Due to their structural tunability, diverse electronic behaviors, and scalability, TMDCs continue to draw significant interest for applications spanning electronics, photonics, energy storage, catalysis, and biosensing.

2.3. MXens

MXenes are a class of 2D transition metal carbides, nitrides, or carbonitrides, typically expressed by the formula M_n+1X_nT_x, where M is an early transition metal, X is carbon and/or nitrogen, and T_x represents surface terminations including –OH, –O, and –F [72]. These materials are synthesized from MAX phases (M_n+1AX_n), in which A is a group 13 to 16 elements, most commonly aluminum, through selective chemical etching of the A layer using hydrofluoric acid or other suitable etchants. This top-down synthesis approach enables the removal of the A element while preserving the strong metallic M–X bonds, resulting in ultrathin, high-aspect-ratio 2D sheets with hydrophilic surfaces and high conductivity [73].

MXenes exhibit a rare synergy of metallic conductivity (up to ~10⁴ S/cm), hydrophilicity, mechanical flexibility, and tunable surface chemistry, which together make them highly versatile materials for numerous advanced technologies [73]. Their high surface area, interlayer spacing, and rich surface functionalities enable efficient intercalation of ions and molecules, facilitating their use in energy storage (e.g., supercapacitors and Li-ion batteries), catalysis, electromagnetic interference (EMI) shielding, and especially biosensing applications [74,75,76,77]. In the context of biosensing, MXenes offer significant advantages: their high electrical conductivity supports rapid electron transfer kinetics; their surface terminations promote excellent aqueous dispersibility and biocompatibility; and their modifiable surfaces allow conjugation with biomolecules, such as antibodies, enzymes, or DNA probes, enabling selective and sensitive detection of target analytes [78,79,80,81]. Furthermore, their 2D morphology offers a large and accessible platform for immobilizing biorecognition elements with high density, thereby improving detection limits and analytical reliability.

2.4. Nitride and Carbonitride-Based Materials

In biosensing applications, especially in field-effect transistors (FETs), nitride-based materials have emerged as promising candidates. While silicon-based materials have traditionally dominated the biosensor field, nitride-based alternatives such as silicon nitride (Si₃N₄) and boron nitride (BN) are gaining increasing attention due to their unique physicochemical properties [82,83,84]. Among them, hexagonal boron nitride (h-BN) exhibits several characteristics that make it particularly attractive for biosensing. It is highly biocompatible, inducing minimal immune responses or cytotoxicity, thus allowing for safe interaction with biological samples [85,86,87]. Its chemical inertness prevents non-specific reactions and fouling, thereby improving sensing accuracy. Additionally, h-BN possesses a smooth atomic surface and high mechanical strength, which contributes to sensor durability during repeated use [88,89].

Silicon nitride (Si₃N₄), widely used in microelectronics, is another nitride-based material recognized for its mechanical robustness, thermal stability, and excellent biocompatibility. These properties render it ideal as a substrate for the immobilization of biomolecules such as enzymes, antibodies, or nucleic acids. Si₃N₄-based biosensors have been employed across various transduction mechanisms as electrical, optical, and mechanical components, enhancing versatility in biosensing applications [90,91,92].

In recent years, boron carbonitride (BCN), a ternary compound composed of boron, carbon, and nitrogen, has also attracted attention due to its tunable properties, high electrical conductivity, and structural robustness. BCN materials offer a high surface area suitable for biomolecular interaction and hold potential for future applications in flexible and miniaturized biosensing platforms [93,94,95]. Overall, nitride-based materials present a compelling platform for the development of next-generation substrate-based biosensors. Their chemical stability, biocompatibility, and ease of integration into various platforms, including lab-on-a-chip devices, implantable sensors, and point-of-care diagnostics position them at the forefront of innovation in healthcare monitoring, environmental sensing, and food safety.

2.5. h-BN, Black Phosphorus, and Phosphorene

Hexagonal boron nitride (h-BN) is a 2D material composed of alternating boron and nitrogen atoms arranged in a honeycomb lattice, which is structurally analogous to graphene. Unlike graphene, h-BN is an electrical insulator with a wide bandgap of approximately 5.9 eV. It exhibits high thermal conductivity, excellent chemical inertness, and outstanding mechanical stability. While its lack of electrical conductivity limits its use as an active transducer material, h-BN is widely employed as a supporting substrate or dielectric layer in electronic and biosensing devices. Its atomically smooth surface and biocompatibility enable it to provide a chemically stable interface, which is crucial in biological environments. In biosensor applications, h-BN contributes to the structural integrity and passivation of sensitive components, making it suitable for multifunctional hybrid platforms [8].

Black phosphorus (BP) is a layered semiconductor composed of puckered sheets of phosphorus atoms bonded in an orthorhombic structure. It exhibits a thickness-dependent direct bandgap ranging from ~0.3 eV in bulk to ~2.0 eV in the monolayer, which is highly desirable for tunable optoelectronic applications. BP also demonstrates high carrier mobility (up to ~1000 cm²/V·s) and in-plane anisotropic electrical and optical properties, which enhance its sensitivity to changes in the surrounding environment. The reactive surface chemistry of BP facilitates effective functionalization with biomolecules, allowing for selective and specific molecular recognition. These characteristics make BP highly promising for use in electrochemical, field-effect, and optical biosensors. However, BP is prone to degradation under ambient conditions due to its sensitivity to oxygen and moisture. Therefore, strategies such as surface passivation, encapsulation, or chemical stabilization are necessary for practical biosensing applications [96].

Phosphorene, the monolayer form of black phosphorus, retains a direct bandgap (~1.5–2.0 eV) and exhibits even greater surface sensitivity due to its atomic thickness. This makes it an ideal candidate for high-performance field-effect transistor (FET)-based biosensors that require ultra-sensitive and label-free detection. Phosphorene combines high electrical conductivity with strong surface reactivity, enabling effective interaction with target analytes and biomolecular probes. Moreover, its mechanical flexibility and biocompatibility support its integration into flexible and wearable biosensing devices. Despite its favorable properties, phosphorene also suffers from environmental instability, necessitating the development of robust encapsulation techniques to preserve its functional performance during operation in physiological or atmospheric conditions [96].

Chemical functionalization and structural patterning of graphene and other 2D materials are important for improving biosensing performance in terms of biosensing, which is important for wearable and implantable biosensors. To enhance the biosensing capabilities of 2D materials such as graphene, MoS₂, and their derivatives, chemical functionalization has emerged as a crucial strategy. Given the intrinsically inert surfaces of many pristine 2D materials, direct detection of specific biomolecules is often limited by poor selectivity and low interfacial affinity. Chemical functionalization addresses these limitations by introducing reactive functional groups or biorecognition elements to the 2D surface, thereby significantly improving selectivity, sensitivity, and biocompatibility [97].

There are two primary approaches to functionalization: covalent and non-covalent modification. Covalent functionalization involves forming stable chemical bonds with surface atoms, typically through oxygen-containing groups such as carboxyl (-COOH), hydroxyl (-OH), or epoxy groups (-C–O–C) [97,98]. This approach enables robust attachment of biomolecules, including antibodies, enzymes, and DNA aptamers, often via carbodiimide chemistry (e.g., EDC/NHS coupling) [24,99,100,101]. However, this method may disrupt the electronic conjugation of the 2D lattice, potentially degrading the material’s intrinsic electronic properties. Non-covalent functionalization, on the other hand, preserves the pristine structure by relying on π–π stacking, van der Waals forces, or electrostatic interactions. Pyrene derivatives, for example, are frequently used as molecular linkers due to their strong affinity for sp²-carbon systems and their ability to anchor biomolecules without altering conductivity [102,103].

Recent advances also explore hybrid functionalization techniques that combine 2D materials with metallic nanoparticles, quantum dots, or metal oxides to create multifunctional biosensing interfaces. For instance, gold nanoparticle-decorated MoS₂ functionalized with DNA aptamers has demonstrated femtomolar sensitivity toward cancer biomarkers [104,105]. These functionalization strategies not only amplify sensor responses but also allow integration into wearable or implantable platforms by facilitating compatibility with flexible substrates and biological tissues.

Overall, chemical functionalization provides a versatile and effective means of tuning the surface chemistry of 2D materials, enabling their application in next-generation biosensing technologies across a variety of clinical and environmental settings.

Recent advances in the structural patterning of 2D materials have provided novel opportunities to amplify biosensing signals and enhance biomolecular recognition. Unlike conventional flat films, patterned 2D nanostructures such as nanoribbons, nanopores, nanohole arrays, and wrinkled surfaces can significantly increase the effective surface area, provide spatial confinement, and modulate local electric fields at the interface. All of these factors contribute to improved sensitivity and selectivity in biosensor platforms [106].

Techniques for structural patterning include electron beam lithography, laser interference lithography, nanoimprinting, and strain-induced buckling, each enabling precise control over nanoscale geometry. For example, mild lithography techniques employ low-energy processing methods such as soft lithographic stamps and polymer-based masking to minimize structural and chemical damage to fragile 2D materials [107,108]. These approaches enable scalable and reproducible patterning suitable for device integration. In contrast, kirigami- and origami-inspired methods utilize strategically designed mechanical cuts and folds to impart three-dimensional deformation and enhanced mechanical flexibility to 2D sheets, thereby providing innovative routes toward stretchable and reconfigurable electronic and actuator systems [109]. The convergence of chemically functionalized and structurally patterned 2D materials with wearable and implantable biosensing platforms is ushering in a new era of bioelectronic interfaces. Given the unique physiological and mechanical challenges posed by on-skin and in-body applications, 2D materials offer an optimal combination of high sensitivity, large surface area, and intrinsic mechanical flexibility. When integrated onto flexible substrates or biocompatible scaffolds, these materials can maintain intimate contact with dynamic, curvilinear biological surfaces, enabling stable, real-time biomonitoring [110,111].

3. 3D Materials for Biosensing Applications

In recent years, 2D materials have attracted significant attention as promising candidates for biosensing applications, primarily due to their distinctive physicochemical properties such as exceptionally high surface-to-volume ratio, tunable electronic characteristics, and inherent mechanical flexibility [2]. Among the various application domains, particular attention has been directed toward wearable and implantable biosensing platforms as they represent two of the most impactful and rapidly advancing areas for real-world integration [112].

Wearable biosensors are designed for non-invasive, real-time monitoring of physiological signals through skin contact or textile integration. The inherent flexibility, transparency, and conductivity of 2D materials make them ideal for such applications, enabling seamless interfacing with the human body [113]. In contrast, implantable biosensors require materials with excellent biocompatibility, chemical stability, and minimal invasiveness, attributes that 2D materials can satisfy due to their nanoscale thickness and functional surface chemistry. These sensors enable continuous monitoring of critical biochemical markers within the body and open avenues for closed-loop therapeutic systems [114].

By simultaneously addressing the material requirements of both wearable and implantable platforms, 2D materials are driving the development of next-generation bio-converged devices that bridge the gap between real-time physiological monitoring and personalized healthcare [115].

3.1. Wearable Sensor

It is an established fact that biological fluids exuded from the body contain a variety of metabolites and ions. These are useful for tracking and diagnosing events in the body [116,117,118,119]. Non-invasive wearable sensing involves contact with the body to detect substances in biofluids, which is a more user-friendly approach than insertion into the body. To achieve more effective wearable biosensing, it is advantageous to combine 2D materials and bioreceptors, with the resultant synergistic effect providing both flexibility for attachment and selectivity for biomarkers [1,4,120] (Figure 3). This combination has been shown to achieve superior performance in the detection of biomarkers from the skin, eye, and oral cavity (Table 1).

Graphene, a carbon material with an sp2 structure, has been utilized in various combinations for biosensing applications [121,122]. The utilization of graphene-antibody sensors constitutes a notable approach in the field as they can detect target substances in biofluids that contain a mixture of different substances. Ku et al. developed a wireless, battery-free graphene FET immunosensor conjugated with a near-field communication device and a transparent, stretchable antenna within a contact lens for monitoring cortisol in biofluid [123]. The sensor revealed a limit of detection (LOD) of 10 pg/mL for cortisol and demonstrated linearity within the range of 1 to 40 ng/mL. The sensor demonstrated stability in diverse temperature and solution conditions, indicating its suitability for reliable detection in in vivo experiments. When worn on a rabbit, the lens demonstrated a response to cortisol concentrations and exhibited no abnormalities in wearability. The pilot trial with a human also exhibited analogous patterns (Figure 4). In another study, glucose was chosen as monitoring target for healthcare application. Ma et al. fabricated an electrochemical biosensor combined with textile for wear and Prussian blue-graphene film for the detection of H₂O₂ from glucose oxidase [124]. Prussian blue functioned as an efficient electrocatalyst for H₂O₂₂ reduction, while graphene enhanced conductivity and mechanical flexibility. Additionally, through immobilization of glucose oxidase, the sensor exhibited a linear range of 0.1 to 20 mM, a high sensitivity of 17.73 µA mM⁻¹ cm⁻², and a LOD of 9.7 µM. Furthermore, it demonstrated stable and reproducible performance during beverage and on-body testing. This high-performance, skin-adherent device highlights the potential of such material combinations for next-generation, non-invasive, real-time glucose monitoring systems. Building on similar strategies that leverage hybrid nanomaterials for wearable biosensing, a flexible and regenerative aptamer-based FET biosensor was reported, which used a graphene–Nafion composite for real-time monitoring of cytokine storms [125]. The sensor employed specific aptamers into a conductive graphene stabilized by Nafion to enhance IFN-γ detection selectivity, and mechanical durability. It demonstrated a remarkable LOD of 880fM in undiluted biofluids. Notably, the sensor retained functionality after multiple regeneration (up to 80) and crumpling (up to 100) cycles, underscoring its suitability for continuous, non-invasive monitoring. This work highlights the potential of functional nanocomposites in developing robust, skin-compatible biosensors for wearable healthcare platforms (Figure 5). As another biomarker for monitoring using electrochemical biosensing, Sun et al. introduced an ultrathin graphdiyne/graphene heterostructure as a stable and sensitive sensor for ascorbic acid and uric acid [126]. Graphdiyne provided abundant active sites and high charge carrier mobility, while graphene offered mechanical strength and excellent conductivity, creating a synergistic interface for efficient electron transfer. Graphdiyne/graphene interacted with heavy metal ions and toxic molecules through d–π and π–π interactions, resulting in reliable detection ability in river and lake water. Furthermore, hemin immobilization enhanced the sensing ability for ascorbic acid and uric acid. The resulting sensor achieved a LOD of 0.27 and 0.081 µM for each target, and a broad linear range going from 1 to 300 µM (as ascorbic acid, up to 2900 µM) for potential medical diagnosis applications. It also demonstrated over 95% selectivity against interference, thermal stability from 20 to 70 °C, and 98% reproducibility during 10 times.

As one of the two-dimensional materials, 2D layered TMDCs have been applied in the biomedical field due to their high biocompatibility [127], but their combination with biomaterials to improve sensing capabilities is being investigated. As an approach to integrating TMDC-based biosensors into wearable contact lenses, Guo et al. presented a smart contact lens sensor incorporating multifunctional MoS₂ transistors [128]. The system utilized monolayer MoS₂ as the active semiconducting material due to its mechanical flexibility, high carrier mobility, and optical transparency, making it well-suited for eye-mounted electronics. Integrating polyimide, gold layer, and glucose oxidase enables a multifunctional FET biosensor system with optical, temperature, and glucose detection. The integrated sensor enabled simultaneous sensing of multiple biomarkers, including glucose and temperature. Through glucose oxidase immobilization, sensitivity to glucose showed 1794.4 µA mM⁻¹ cm⁻² over a linear range of 0 to 1 mM. Also, the sensor exhibited high thermal sensitivity of 0.94 Ω/°C, high optical transmittance of over 93%, and low haze of less than 3%. Wireless data transmission and power delivery were also incorporated, allowing real-time monitoring without external wiring. This study demonstrates the feasibility of multifunctional, transparent biosensors integrated directly into everyday devices for continuous health monitoring. In a further application of enzymatic systems in wearable biosensing, Weng et al. presented a nanozyme-enzyme electrochemical biosensor for the monitoring of lactate in sweat [129]. The device, fabricated on a flexible polyimide film, integrates a Janus textile to facilitate unidirectional sweat transport. This working electrode was based on laser-scribed graphene modified with CeO₂-MoS₂ nanozymes and gold nanoparticles. It provided strong electrocatalytic activity for the reduction in H₂O₂ formed by lactate oxidase, resulting in indirect measurements of the concentration in sweat lactate. Upon immobilization of lactate oxidase, the biosensor exhibited detection capabilities with a linear range of 0.1–50.0 mM, a LOD of 0.135 mM, and a sensitivity of 25.58 μA mM⁻¹ cm⁻². Lactate detection in artificial sweat showed a strong correlation with enzyme-linked immunosorbent assay results, and on-body tests during exercise confirmed its practical performance. The system also demonstrated fast response times (~2 min), good stability, and suitability for low-cost production, supporting its potential use in sports monitoring and non-invasive healthcare diagnostics.

MXene belongs to a class of carbon materials, composed of early transition metals and carbon (or nitride), with various surface functional groups, such as hydroxide and oxide [130,131]. Shi et al. introduced a battery-free smart bandage that incorporates MXene-based peptide-functionalized biosensors for real-time monitoring of wound infections [132]. The sensor targeted two key bacterial virulence biomarkers (sortase A from Staphylococcus aureus and pyocyanin from Pseudomonas aeruginosa), detected using differential pulse voltammetry. Ti₃C₂Tx MXene was employed to enhance electrode conductivity and sensitivity, and a ferrocene-labeled peptide was immobilized to recognize sortase A. The device showed reliable linearity and selectivity to detection ranges of 1 pg/mL to 100 ng/mL for sortase A and 1 to 100 μM for pyocyanin. The device showed reliable linearity and selectivity to detection ranges of 1 pg/mL to 100 ng/mL for sortase A and 1 to 100 μM for pyocyanin. Integration of smart bandage and near-field communication enabled wireless power harvesting and smartphone-based data readout. In rat models, the biosensor confirmed its capability for multi-biomarker tracking of infected wounds. This fully integrated, wearable platform offers a practical solution for point-of-care infection management and personalized wound care (Figure 6).

Expanding on the integration of catalytically active nanomaterials in wearable biosensing, Khan et al. reported a multifunctional MXene-based platform incorporating cerium oxide nanoparticles (MXCe₂) for enhanced enzyme-based electrochemical biosensors [133]. The MXCeO₂ composite, synthesized from Ti₃C₂ MXene and CeO₂ nanoclusters, provided high surface area, conductivity, and strong catalytic activity toward H₂O₂ reduction. This enabled efficient immobilization and amplification of oxidase enzyme reactions, which they demonstrated using glucose oxidase, lactate oxidase, and xanthine oxidase. The biosensors demonstrated a LODs of 0.8 μM for H₂O₂, 0.49 μM for glucose, 3.6 μM for lactate, and 1.7 μM for hypoxanthine. The MXCeO₂ was successfully integrated into a wearable platform for sweat analysis, showing reliable lactate detection under physiological conditions. The synergistic combination of nanozyme activity and enzyme specificity supports MXCeO₂ as a platform for powerful, flexible biosensors suitable for wearable, real-time biochemical monitoring.

Graphitic carbon nitride (g-C₃N₄) is a multifunctional 2D-carbon material that has been extensively studied for applications beyond catalysis, including bioimaging and biosensing, due to its low cost, strong biocompatibility, and minimal toxicity [134,135]. For developing flexible and durable biosensing platforms, Chiu et al. introduced a wearable sweat biosensor based on carbon nitride quantum dots integrated with polyaniline nanocomposites for glucose monitoring [136]. The carbon nitride quantum dots, featuring high surface area and abundant edge sites, enhanced the electron transfer efficiency and ion mobility of polyaniline. At the same time, pyridinic nitrogen functionalities improved conductivity under neutral pH and electrochemical activity. Upon immobilization of glucose oxidase, the developed sensor electrode achieved a glucose sensitivity of 49.71 ± 0.45 μA mM⁻¹ cm⁻², and demonstrated excellent electrocatalytic activity for H₂O₂ detection with 95.47 ± 1.31 μA mM⁻¹ cm⁻². Repeated mechanical bending does not affect the performance and structure of the electrode. This nanocomposite system offers promising mechanical resilience, electrochemical performance, and selectivity, supporting its applicability in real-time, on-body glucose monitoring for diabetes care.

Table 1. Summary of wearable biosensors using functional nanomaterials for non-invasive detection of biochemical and environmental markers.

Materials		Target	Features	Ref.
Graphene	Antibody	Cortisol	- Wireless biosensing contact lens of cortisol in human tear	[123]
	Antibody Fab Ag nanofiber	MMP-9	- Real-time monitoring and therapeutic device for chronic ocular surface inflammation	[137]
	Prussian blue Glucos oxidase	Glucose	- Real-time detection in commercial beverages and human sweat between pre- and post-meal	[124]
	Aptamer	IFN-γ	- Background signal decrease due to Nafion - Detection in undiluted human sweat	[125]
	Anti-bovine antibody	IFN-γ IL-10	- Label-free monitoring of immune response	[138]
	Aptamer	IFN-γ TNF-α IL-6	- Cytikine detection in human serum, urine, and saliva - Wearable application on different human body parts	[139]
	Boron ion CNT	Uric acid	- Enzyme-free and matel-free electrochemical sensor using human sweat	[140]
	Graphdiyne Hemin	Ascorbic acid Uric acid	- Detection of environmental pollutants without hemin and medical diagnosis with hemin	[126]
	Au cluster Chitosan	Uric acid pH	- Simultaneous long-term monitoring in human sweat	[141]
	Silk fibroin LiBr	Humidity	- Self-powered respiratory monitoring, diagnosing, and treatment system	[142]
	WS2	Humidity	- Wireless sensing of human breath and speech	[143]
	-	Uric acid Thyrosine	- Detection in patients and healthy subjects for gout monitoring	[144]
	Artificial antibody	Metabolites Nutrients	- Wireless biomarker and nutrient monitoring according to activities and supplement intake	[145]
TMDC	Glucose oxidase	Glucose	- Multifunctional soft contact lens sensing system	[128]
	Anodic aluminum oxide	Humidity	- Honeycomb-like nanotube biosensor for skin and breath	[146]
	Polyaniline	pH	- Sensitive weat pH sensor against ions and metabolites	[147]
	CeO2-MoS2 AuNP Lactate oxidase	Lactate	- Collaboration with nanozyme and enzyme for lactate detection in human sweat	[129]
	Prussian blue TiO2	H2O2 Phospho- protein	- Oxidative stress monitoring using human sweat	[148]
Mxene	Cellulose	Humidity	- Smart fabrics for breath monitoring, thermotherapy, and wound dressing	[149]
	Nanoporous carbon Glucose oxidase	Glucose	- Epidermal patch for chemical and physical parameters	[150]
	ZnO Glucose oxidase	Glucose	- Real-time monitoring in sweat before and after sweets intake	[151]
	AuNP Peptide	Sortase A Pyocyanin	- Smart bandage for wound monitoring about bacterial infection	[132]
	CeO2NP Oxidase enzymes	H2O2 Glucose Lactate Hypoxanthine	- Biosensing platform for boosting efficiency of oxidase enzymes	[133]
	PyTs	Uric acid	- Real-time monitoring in human sweat according to intake of purine-rich food	[152]
Carbon Nitride (g-C3N4)	Polyaniline Glucose oxidase	Glucose	- Sweat-based biosensor using H2O2-sensitive nanocomposite and glucose oxidase	[136]
	CeO2 nanoparticle	Humidity Skin dryness	- Self-powered multifunctional sensing for respiratory and skin dryness	[153]

CNT: carbon nanotube, NP: nanoparticle, PyTs: 1,3,6,8-pyrene tetrasulfonic acid sodium salt.

Table 1. Summary of wearable biosensors using functional nanomaterials for non-invasive detection of biochemical and environmental markers.

Materials		Target	Features	Ref.
Graphene	Antibody	Cortisol	- Wireless biosensing contact lens of cortisol in human tear	[123]
	Antibody Fab Ag nanofiber	MMP-9	- Real-time monitoring and therapeutic device for chronic ocular surface inflammation	[137]
	Prussian blue Glucos oxidase	Glucose	- Real-time detection in commercial beverages and human sweat between pre- and post-meal	[124]
	Aptamer	IFN-γ	- Background signal decrease due to Nafion - Detection in undiluted human sweat	[125]
	Anti-bovine antibody	IFN-γ IL-10	- Label-free monitoring of immune response	[138]
	Aptamer	IFN-γ TNF-α IL-6	- Cytikine detection in human serum, urine, and saliva - Wearable application on different human body parts	[139]
	Boron ion CNT	Uric acid	- Enzyme-free and matel-free electrochemical sensor using human sweat	[140]
	Graphdiyne Hemin	Ascorbic acid Uric acid	- Detection of environmental pollutants without hemin and medical diagnosis with hemin	[126]
	Au cluster Chitosan	Uric acid pH	- Simultaneous long-term monitoring in human sweat	[141]
	Silk fibroin LiBr	Humidity	- Self-powered respiratory monitoring, diagnosing, and treatment system	[142]
	WS2	Humidity	- Wireless sensing of human breath and speech	[143]
	-	Uric acid Thyrosine	- Detection in patients and healthy subjects for gout monitoring	[144]
	Artificial antibody	Metabolites Nutrients	- Wireless biomarker and nutrient monitoring according to activities and supplement intake	[145]
TMDC	Glucose oxidase	Glucose	- Multifunctional soft contact lens sensing system	[128]
	Anodic aluminum oxide	Humidity	- Honeycomb-like nanotube biosensor for skin and breath	[146]
	Polyaniline	pH	- Sensitive weat pH sensor against ions and metabolites	[147]
	CeO2-MoS2 AuNP Lactate oxidase	Lactate	- Collaboration with nanozyme and enzyme for lactate detection in human sweat	[129]
	Prussian blue TiO2	H2O2 Phospho- protein	- Oxidative stress monitoring using human sweat	[148]
Mxene	Cellulose	Humidity	- Smart fabrics for breath monitoring, thermotherapy, and wound dressing	[149]
	Nanoporous carbon Glucose oxidase	Glucose	- Epidermal patch for chemical and physical parameters	[150]
	ZnO Glucose oxidase	Glucose	- Real-time monitoring in sweat before and after sweets intake	[151]
	AuNP Peptide	Sortase A Pyocyanin	- Smart bandage for wound monitoring about bacterial infection	[132]
	CeO2NP Oxidase enzymes	H2O2 Glucose Lactate Hypoxanthine	- Biosensing platform for boosting efficiency of oxidase enzymes	[133]
	PyTs	Uric acid	- Real-time monitoring in human sweat according to intake of purine-rich food	[152]
Carbon Nitride (g-C3N4)	Polyaniline Glucose oxidase	Glucose	- Sweat-based biosensor using H2O2-sensitive nanocomposite and glucose oxidase	[136]
	CeO2 nanoparticle	Humidity Skin dryness	- Self-powered multifunctional sensing for respiratory and skin dryness	[153]

CNT: carbon nanotube, NP: nanoparticle, PyTs: 1,3,6,8-pyrene tetrasulfonic acid sodium salt.

3.2. Implantable Sensor

Implantable biosensors are miniaturized analytical devices designed to monitor physiological signals or biomolecules directly within the body (Figure 7). These biosensors have been developed for real-time and continuous tracking of biomarkers (e.g., glucose, neurotransmitters, and tumor markers) present in the body as well as those secreted outside the body, providing important insights into disease progression and treatment efficacy [154,155] (

Table 2. Summary of implantable biosensors utilizing advanced nanomaterials for in vivo monitoring of physiological and pathological biomarkers.

Materials		Target	Features	Ref.
Graphene	Aptamer	Dopamine	- Real-time neurochemical monitoring about pharmacological stimulation	[158]
	Au nanoparticle Antibody	Carcinoembryonic antigen	- Wireless antenna immunosensor	[159]
	Silicon carbide	Dopamine	- Porous nanoforest structure favorable for dopamine oxidation	[160]
	Platinum nanoparticle Lactate oxidase	Lactate Potassium ion	- Saliva-based sensing for real-time personalized healthcare	[161]
TMDC	MoS2	Temperature Pressure	- Mesh structure design for unfolding in body	[157]
MXene	Resveratrol Silver nanowire Antibody	Glial fibrillary acidic protein	- Suppression of neuronal damage and inflammation by resveratrol - Biomarker pattern analysis for traumatic brain injury	[156]

).

To achieve real-time, high-resolution monitoring of neurochemical activity, Wu et al. introduced an implantable aptamer-functionalized graphene microtransistor for in vivo dopamine sensing [158]. The structural change induced by binding to dopamine and aptamer altered the gate voltage-dependent carriers on graphene, enabling sensitive and immediate detection of dopamine. The biosensor revealed a LOD of 10 pM and molecular selectivity greater than 19-fold over norepinephrine using dopamine-binding aptamers. The system exhibited nearly cellular-scale spatial resolution with fast response dynamics (on time: 2.09 s and off time: 5.38 s), enabling precise detection of transient dopamine release. Real-time monitoring in mouse models through pharmacological stimulation established the implantable platform’s potential for capturing dopamine dynamics in the brain. Furthermore, the probe’s modular design allows for easy adaptation to other neurochemicals by replacing the surface-bound aptamer, suggesting broad potential in neuroscience research and neurodegenerative disease monitoring (Figure 8). As another implantable biosensor using graphene, a compact wireless antenna immunosensor for carcinoembryonic antigen (CEA) detection was introduced utilizing a gold nanoparticle-decorated graphene film [159]. The biosensor integrates a miniaturized antenna (5 × 3 × 0.127 mm³) with a double symmetric bending structure, functioning dually as both radiator and sensing element. AuNPs synthesized by thermal reduction were deposited on CVD-grown graphene, enhancing the film’s immunoreactivity and conductivity. Through immobilization of antibodies against the CEA, this configuration achieved a sensitivity of 2.46 MHz/log(ng mL⁻¹) over a wide CEA concentration range (0.01–100 ng mL⁻¹). The system exhibited high specificity, long-term stability, and reliable performance in real human serum with recovery rates between 93.5% and 100.2%. These features underscore its potential for continuous, real-time tumor biomarker monitoring in clinical and home-care settings.

For the advancement of minimally invasive neural interfaces, an injectable 2D-material-based sensor array was developed to monitor and treat brain disorders with minimal surgical intervention [157]. The array comprises graphene-based multi-channel electrodes for electrocorticography and electrical stimulation, and MoS₂-based sensors for intracranial temperature and pressure monitoring. Fabricated in a flexible mesh structure, the device can be delivered through a small cranial opening (1–2 mm) and self-expand to conform to the brain surface. In vivo studies in rabbits demonstrated effective seizure detection and suppression, along with real-time temperature and pressure tracking. The graphene electrodes provided high signal-to-noise ratios and efficient charge transfer, while the MoS₂ elements exhibited stable responses to physiological variations. This strategy highlights the potential of 2D nanomaterials in creating compact, multifunctional brain implants with reduced surgical burden.

A polyphenol-functionalized MXene-based FET biopatch was developed to enable real-time, in situ monitoring of neurochemicals in damaged brain tissue, specifically for the spatiotemporal tracking of traumatic brain injury (TBI) biomarkers [156]. This biopatch integrates Ag nanowire-doped MXene as the semiconductor, offering enhanced conductivity and sensitivity, while resveratrol provides anti-inflammatory and neuroprotective functionality. The device achieved ultra-sensitive detection of glial fibrillary acidic protein, a key TBI biomarker, with a LOD of 0.47 pg/mL and high reproducibility (RSD = 2.12%). In vivo application in a TBI rat model revealed dynamic GFAP diffusion from the injury core to the periphery over time, confirming its capacity for real-time spatiotemporal biochemical mapping. This platform offers a promising direction for dissecting the molecular pathophysiology of TBI and other neurological disorders (Figure 9).

The flexibility and large surface area of 2D materials are advantageous for application to the body, where there is a lot of movement. In addition, combinations with various functional materials improve detection efficiency and selectivity, and are being developed into wearable and implantable biosensors that detect disease markers, metabolites, hormones, etc.

Table 3. Quantitative comparisons of 2D-materials-based biosensors.

Target	Materials	LOD	Sensitivity	Linear Range	Ref.
Glucose	PB-RGO/GOx	7.94 μM	27.78 μA mM −1 cm−2	0–4 mM, 4–8 mM	[124]
	MoS2/Au/PI/GOx	0.1 mM	1794.4 μA mM −1 cm−2	-	[128]
	NPC@MXene/PtNPs/GOx	7 μM	100.85 μA mM −1 cm−2	3 μM–21 mM	[150]
	ZnO TPs/MXene/GOx	17 μM	29 μA mM −1 cm−2	50–700 μM	[151]
	MXene/CeO2NP/GOx	0.49 μM	7.6 μA/μM	100 μM–10 mM	[133]
	GOx/CNQDs/PANI	0.029 μM	49.71 μA μM −1 cm−2	0–500 μM	[136]
Uric acid	BGQDs/CNTs	0.99 μM	8.92 μA μM −1 cm−2	0–50 μM	[140]
	Hemin/GDY/G/GCE	0.081 μM	-	1–300 μM	[126]
	Chitosan-Au-LIG	0.5 μM	3.11 μA μM −1 cm−2	0–100 μM	[141]
	LEG	0.74 μM	3.50 μA μM−1 cm−2	-	[144]
	PyTS@Ti3C2Tx	0.029 μM	49.71 μA μM−1 cm−2	10–100 μM	[152]

LOD: limit of detection; PB: Prussian blue; RGO: reduced graphene oxide; GOx: glucose oxidase; PI: polyimide; NPC: nanoporous carbon; NP: nanoparticle; TP: tetrapod; CNQD: carbon nitride quantum dot; PANI: polyaniline; BGQD: boron-doped graphene quantum dot; CNT: carbon nanotube; GDY: graphdiyne; GCE: glassy carbon electrode; LIG: laser-induced graphene; and LEG: laser-engraved graphene PyTS: 1,3,6,8-pyrene tetrasulfonic acid sodium salt.

summarizes the biosensors mentioned above that were selected for quantitative comparison based on their identical targets.

4. Challenges and Future Perspectives

The biomedical and biosensor advancement of 2D-material-based sensors faces several significant obstacles. Foremost among these is the necessity of obtaining approval from stringent regulatory authorities, which often express concerns regarding the potential toxicity and biocompatibility of novel materials [162] (Figure 10).

The 2D nanomaterials have expanded from graphene to include TMDCs, BP, and MXenes. These materials have demonstrated significant potential in various applications, including electrochemistry, energy storage, biosensors, drug delivery, and tissue regeneration, garnering attention from both academia and industry [3]. However, as the large-scale production and commercialization of these materials progress, concerns regarding their potential toxicity when exposed to humans or the environment have also increased. Particularly, understanding the biological reactivity and in vivo mechanisms of action of these materials has become an essential task in addressing their safety implications [163,164,165,166,167].

The toxicity of 2D nanomaterials arises not merely from their elemental composition but from a complex interplay of multiple physicochemical properties, including particle size, surface characteristics, degree of functionalization, and the presence of impurities [2,115]. Among these factors, dosage and exposure duration are directly correlated with the intensity of cytotoxic effects, while the size and morphology of the particles critically influence cellular uptake routes and intracellular accumulation patterns [168,169,170]. Furthermore, surface charge and the extent of surface functionalization are key determinants of colloidal stability in biological environments and modulate interactions with proteins, ultimately governing cellular responses. For example, tailored surface functionalization can regulate endocytosis, modulate immune activation, or reduce non-specific adsorption, while precise size control can influence membrane penetration efficiency and the generation of reactive oxygen species (ROS) [171,172]. These considerations are essential for designing 2D nanomaterials with improved biosafety profiles, particularly for biomedical and biosensor applications such as diagnostics, drug delivery, and tissue engineering.

The 2D nanomaterials interact with biological systems through a combination of chemical, mechanical, and electrochemical mechanisms, each contributing to distinct cellular responses. Chemically, these materials can degrade or release reactive ions and molecules that interfere with intracellular signaling pathways, enzymatic functions, or membrane integrity, leading to cytotoxic or genotoxic effects [163,173]. Mechanically, the sharp edges, ultrathin morphology, flexibility, and hydrophobic surface of many 2D nanostructures may disrupt lipid bilayers, induce membrane perforation, or generate mechanical stress on the cytoskeleton [174,175]. In terms of electrochemical interactions, 2D nanomaterials may act as redox-active surfaces or catalytic agents, promoting electron transfer processes that generate ROS [176,177,178,179]. The accumulation of ROS within cells leads to oxidative stress, mitochondrial dysfunction, and the activation of apoptosis signaling cascades [177,180]. Together, these mechanisms highlight the multifaceted nature of 2D-nanomaterial-induced toxicity and underscore the importance of comprehensive biocompatibility assessments prior to their implementation in clinical or environmental settings.

BP, also known as phosphorene in its monolayer form, is particularly notable for its intrinsic biodegradability. Upon exposure to ambient oxygen and moisture, BP undergoes rapid oxidation and hydrolysis, resulting in the formation of soluble phosphate ions (PO₄³⁻), which are non-toxic and readily metabolized in biological systems. This property renders BP highly advantageous for short-term, disposable, or bioresorbable biosensors. However, the degradation kinetics of BP are highly sensitive to environmental variables such as pH, light, oxygen concentration, and humidity. While this responsiveness can be harnessed for temporal control over device function, it also imposes limitations on long-term stability, necessitating further research into stabilization strategies or controlled degradation mechanisms [181,182,183,184,185]. In contrast, TMDCs such as molybdenum disulfide (MoS₂) and tungsten disulfide (WS₂) exhibit comparatively higher chemical stability due to their strong covalent bonding within layers. Nonetheless, studies have shown that these materials are not entirely inert in biological settings. MoS₂, for instance, can undergo gradual oxidative degradation in the presence of reactive oxygen species (ROS), forming molybdate ions and other soluble species. The rate of this degradation is influenced by nanosheet size, crystallinity, and surface chemistry, with smaller nanosheets degrading more rapidly. However, despite these observations, comprehensive kinetic studies on TMDC biodegradability remain limited, and systematic evaluation of their in vivo fate, transformation, and clearance is still required [186,187]. MXenes (e.g., Ti₃C₂T_x), a family of transition metal carbides and nitrides, present another promising class of biosensor materials, owing to their high conductivity and hydrophilic surfaces. However, they are also known to be susceptible to environmental oxidation, leading to the formation of surface titanium dioxide (TiO₂) layers. These oxidized products are considered relatively biocompatible, yet uncontrolled degradation can compromise device functionality. The lack of detailed studies quantifying the biodegradation rates of MXenes under various physiological and biochemical conditions highlights a major knowledge gap. Developing robust models to understand their degradation pathways and products is essential for ensuring their long-term biosafety and operational reliability in biomedical applications [188,189,190,191].

In summary, while the biodegradable nature of certain 2D materials like BP offers unique advantages for temporary biomedical devices, the incomplete understanding of degradation mechanisms for TMDCs and MXenes calls for further research. Elucidating these pathways is crucial for balancing device performance, safety, and sustainability in next-generation biosensing technologies.

Recent advances in artificial sensing technologies such as electronic nose (E-nose) and electronic tongue (E-tongue) systems have demonstrated significant potential in various biosensing applications, including disease diagnosis, food quality assessment, and environmental monitoring. The E-nose, which mimics the human olfactory system, enables non-invasive detection of volatile organic compounds (VOCs) in exhaled breath. Through the integration of high-sensitivity sensor arrays and advanced pattern recognition algorithms, E-nose systems have shown promise as practical tools for early disease detection and real-time health monitoring [110]. Similarly, E-tongue devices emulate human gustatory receptors to detect a wide range of ions and molecules. Recent developments have introduced bioinspired triboelectric E-tongue systems capable of self-powered operation without external energy sources. These systems exhibit high sensitivity and selectivity in complex biochemical samples, indicating their strong potential for personalized diagnostic platforms [111]. Although E-nose and E-tongue technologies are currently more prevalent in analytical and diagnostic contexts rather than in wearable or implantable formats, rapid progress in flexible electronics, nanomaterials, and biocompatible sensor integration is narrowing this gap. These advances are expected to facilitate the incorporation of artificial chemosensory systems into next-generation smart healthcare devices, underscoring their potential as critical components in future personalized health monitoring systems.

Among various strategies to enhance the biointerface of 2D materials for wearable and implantable biosensing platforms, the integration of biomineral-based components offers unique opportunities. Biominerals such as calcium phosphates, silica, and carbonates naturally formed inorganic materials in biological systems exhibit hierarchical architecture, excellent biocompatibility, and bioactivity. These features make them ideal candidates for hybridizing with 2D materials to improve biological affinity, interface stability, and functional performance in physiological environments [192,193,194,195]. For instance, diatom biosilica, with its intrinsic nano–micro porous structure, can serve as a biofunctional scaffold to support 2D-material immobilization [196,197]. This integration enables improved antimicrobial, hemostatic, and drug delivery functions.

Similarly, the incorporation of carbonated apatite derived from the biomimetic transformation of vaterite into bone-like composites can enhance osteoconductivity and biocompatibility [198,199,200]. When combined with 2D materials for implantable sensor coatings, this approach offers improved biological performance at the material tissue interface. These biomineral-based strategies, when integrated with the electrical conductivity and surface tunability of 2D materials, pave the way for multifunctional, bio-converged systems tailored for next-generation wearable and implantable biosensing applications.

Furthermore, the long-term stability of 2D materials in biological environments is a critical concern that warrants significant attention [201,202]. In the case of electrochemical electrodes, salt solutions can infiltrate the passivating active surface, triggering redox reactions that may result in the degradation of the 2D materials [9]. Additionally, the high electric fields applied across the atomically thin layers can cause alterations in the material’s fine structure, potentially affecting ion current and leading to performance degradation over time [203,204]. This consideration is particularly critical in biomedical applications, including implantable biosensors, targeted drug delivery platforms, and neural interface systems, where the structural or chemical degradation of 2D materials may compromise device functionality, diminish biocompatibility, and potentially elicit adverse physiological responses. Accordingly, a comprehensive understanding of the physicochemical degradation mechanisms of 2D materials under physiologically relevant conditions is imperative to enable their reliable and safe clinical implementation.

5. Conclusions

Two-dimensional (2D) materials, including graphene, TMDCs, MXenes, carbon nitrides, and black phosphorus, offer considerable promise for wearable and implantable biosensors due to their unique physicochemical properties. However, challenges such as long-term stability, controlled biodegradability, scalable production, and lack of standard performance benchmarks hinder clinical translation. Future progress should focus on customized surface functionalization for improved specificity, AI-assisted signal processing for real-time data handling, and the development of energy-efficient, self-powered systems. In implantable applications, time-controlled biodegradability, particularly in materials like black phosphorus, will be crucial. Standardization of metrics such as sensitivity and biocompatibility, along with interdisciplinary collaboration and early regulatory engagement, will be key to bridging the gap between laboratory innovation and real-world deployment. By addressing these priorities, 2D materials are well-positioned to drive the next generation of bio-integrated sensing technologies.