Wearable bioelectronics for skin cancer management.

1.
Introduction
Skin cancer is a major global health concern, including a range of malignancies originating from skin cells [1,2]. The most common types are non-melanoma skin cancers (NMSCs), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), which are localized and highly treatable at an early stage [3,4]. In contrast, melanoma, although less prevalent, is significantly more aggressive due to its high metastatic potential and associated with a higher mortality rate, presenting a considerable clinical challenge [5,6]. Melanoma is easily misdiagnosed or underdiagnosed in the early stage, which not only delays the treatment timing of patients, but also affects the prognosis of patients in serious cases. According to the Global Cancer Statistics 2022, approximately 332,000 new melanoma cases were diagnosed globally, resulting in an estimated 59,000 deaths [7,8]. Although melanoma accounts for only 1.7 % of all newly diagnosed cancers, it contributes disproportionately to skin cancer-related mortality. The prognosis varies significantly with disease stage, with localized melanoma exhibiting a five-year survival rate exceeding 90 %, whereas metastatic melanoma has a survival rate of less than 20 %. Therefore, early detection and intervention of skin cancer are of critical importance [9,10].
Traditional skin cancer management faces several fundamental limitations. Diagnosis has traditionally depended on visual inspection by dermatologists, often aided by dermoscopy to improve the visualization of subtle morphological features [11]. However, the subjective nature of visual assessment can result in diagnostic inaccuracies, especially when differentiating early-stage melanoma from benign pigmented lesions [12]. Histopathological examination of biopsy specimens remains the gold standard for definitive diagnosis, offering essential insights into tumor classification, staging, and the identification of prognostic biomarkers [13]. Nevertheless, it is invasive, can be subject to interpretational variability, and provides only a static snapshot of the tumor. In addition, these screening methods require experienced doctors and specialized medical equipment, which can easily lead to delays in timely skin cancer screening. Treatment strategies for skin cancer are tailored to the tumor type, stage, and anatomical location. NMSCs are typically managed through surgical excision, cryotherapy, or topical therapies [14]. In contrast, melanoma often requires a multimodal approach, including surgical resection, radiotherapy, chemotherapy, targeted therapy, and immunotherapy [15]. However, systemic chemotherapy and radiotherapy are associated with significant off-target toxicities, which limit their efficacy and tolerability [16]. Furthermore, the inherent heterogeneity of melanoma, characterized by distinct mutational profiles between primary and metastatic lesions, poses a major challenge for targeted therapies and contributes to the development of therapeutic resistance [17,18]. Consequently, more effective strategies are urgently needed for skin cancer management.
Wearable bioelectronic offer innovative solutions to address the aforementioned challenges. Wearable bioelectronics, a category of electronic systems fabricated from flexible and stretchable materials, have significantly advanced biomedical applications by facilitating seamless integration with biological tissues [19–23]. In contrast to conventional rigid devices, wearable bioelectronic systems possess mechanical properties—such as a low elastic modulus and high stretch-ability—that closely resemble those of human tissues, thereby ensuring enhanced biocompatibility and functionality [24,25]. The evolution from rigid, silicon-based electronics to highly adaptable, polymer-based platforms has been driven by innovations in materials science and micro/nanofabrication [26–28]. These advancements have enabled the real-time monitoring of various physiological and biochemical parameters, including heart rate [29–37], respiration rate [38–45], eyeball movement [46–50], body temperature [51–55], glucose levels [56–58], electrocardiography (ECG) [59], electromyography (EMG) [60–62], electroencephalography (EEG) [63–69], among others. In the field of skin cancer, wearable devices are becoming increasingly popular. The rapid growth and intense research interest in this interdisciplinary field are evidenced by the exponential increase in scientific publications over the past decades (Fig. 1). The miniaturized and skin-conformal design of wearable electronic devices allows for comfortable, long-term monitoring at home, thereby facilitating the early detection of skin cancer and enhancing patient compliance. Furthermore, by employing optical methods like near-infrared and Raman spectroscopy, these wearable electronic devices can perform non-invasive, high-precision molecular detection of metabolic abnormalities, such as the altered lipid-to-protein ratios that signify malignant transformation [70,71].
Beyond sensing, wearable bioelectronics are evolving into multifunctional platforms capable of delivering active therapeutic interventions, from targeted drug release to electrical stimulation for neuromodulation [72,73]. The integration of biocompatibility, flexibility, stretchability, and minimally invasive operation makes soft bioelectronics a transformative technology in personalized medicine, with promising applications in the management of diabetes, cardiovascular diseases, cancer, and others [74–76]. Wearable bioelectronics are enabling more precise and effective skin cancer therapies. For instance, thermoresponsive hydrogel microneedles can deliver chemotherapy drugs with localized, on-demand control, which enhances efficacy while reducing systemic toxicity [77]. Furthermore, these flexible platforms support combination therapies by providing spatiotemporal control over multiple treatment modalities for synergistic outcomes.
This review systematically examines the latest advancements in wearable bioelectronics for skin cancer diagnosis and treatment. We begin by exploring the pathological mechanisms underlying skin cancer, followed by a comprehensive discussion of foundational biomaterials for wearable bioelectronics. Then the wearable optical and electrochemical sensing devices for skin cancer detection was introduced. Next, we evaluate wearable device platforms for chemotherapy, photodynamic therapy, electrotherapy, and immunotherapy, as well as combination therapies. Then, we discuss the key properties that a wearable device for skin cancer should have, including device integration, mechanical properties, and biocompatibility. Finally, we address key challenges, including technological bottlenecks and clinical translation challenges, while proposing future directions for wearable devices in skin cancer care. Through interdisciplinary innovations, wearable devices have the potential to redefine precision oncology, providing safer, non-invasive, easily accessible, more effective, and personalized solutions for skin cancer care.

2.
Pathophysiological characteristics of skin cancer
Skin cancer comprises a heterogeneous group of malignancies arising from various cellular components of the skin, each with distinct pathophysiological characteristics. Non-melanoma skin cancers, primarily basal cell carcinoma and squamous cell carcinoma, originate from keratinocytes in the epidermis [78]. BCC, typically originating from the basal layer, is characterized by slow, localized growth with minimal metastatic potential [2]. In contrast, SCC arises from the squamous cell layer and presents a more aggressive phenotype, with the potential for regional or distant metastasis, particularly in immunocompromised individuals or those with chronic ultraviolet (UV) exposure [1]. The development of both BCC and SCC is strongly associated with cumulative UV radiation exposure, which induces DNA damage and results in the dysregulation of cell cycle control and apoptosis [79]. Key molecular pathways involved in NMSC pathogenesis include the Hedgehog signaling pathway in BCC and the p53 and RAS pathways in SCC [80–84].
In contrast, cutaneous melanoma arises from melanocytes in the basal layer of the epidermis, with its malignant transformation driven by a series of genetic mutations and epigenetic dysregulation [85]. UV radiation, particularly UVB, is a major causative factor in melanoma, inducing DNA damage—such as the formation of cyclobutane pyrimidine dimers (CPDs)—which contributes to melanocyte malignancy [86]. Early-stage lesions typically present as focal proliferation of atypical melanocytes (radial growth phase), which eventually breach the basement membrane and invade the dermis (vertical growth phase) [87]. At this stage, tumor cells acquire high metastatic potential, disseminating through lymphatic and hematogenous routes to lymph nodes, lungs, liver, and other organs (Fig. 2). Mutations in BRAF V600E, NRAS Q61K, and the TERT promoter have been identified as key drivers of melanoma progression [88–91]. Large-scale genomic profiling of melanoma subtypes has revealed distinct mutational landscapes across cutaneous, acral, and mucosal melanomas, with BRAF, CDKN2A, NRAS, and TP53 being the most commonly mutated genes in cutaneous melanoma [92]. These mutations activate the MAPK/ERK and PI3K/AKT signaling pathways. As illustrated in Fig. 2, activation of these pathways promotes uncontrolled cell proliferation, confers resistance to apoptosis, and enhances the invasive and migratory capabilities of tumor cells. Targeted therapy with BRAF inhibitors has proven effective for BRAF-mutant melanoma, and combination therapy involving BRAF and MEK inhibitors has shown significantly superior efficacy compared to monotherapy [93].
Melanoma biomarker systems integrate genomic, epigenetic, and immune microenvironmental parameters to improve diagnostic and prognostic accuracy. The BRAF V600E mutation is a key genomic marker for both melanoma diagnosis and predicting therapeutic response to targeted agents such as dabrafenib. Next-generation sequencing (NGS) enables the detection of mutated alleles in tissue samples at frequencies as low as 0.01 % [94]. Epigenetically, methylation of circulating tumor DNA (ctDNA) in the RASSF1A gene has emerged as a promising biomarker, detected in approximately 69 % of melanoma cell lines, facilitating early diagnosis and prognosis assessment [95]. Similarly, circulating microRNAs (miRNAs), such as miR-21 and miR-155, are overexpressed by 8.6-fold and 7.5-fold, respectively, in melanoma tissues compared to benign nevi. A meta-analysis demonstrated that their combined detection in liquid biopsy achieved a sensitivity of 87 % and a specificity of 81 % [96,97]. Additionally, the expression of the immune checkpoint molecule PD-L1, assessed via immunohistochemistry, serves as a predictive biomarker for anti-PD-1/PD-L1 therapies. PD-L1-positive patients exhibit an objective response rate (ORR) of 55.6 %, compared to 37.9 % in PD-L1-negative patients—an approximate relative increase of 47 % [98]. Emerging nanoparticle-based fluorescence detection methods have enhanced the sensitivity of PD-L1 detection, offering promising prospects for future diagnostic applications [12]. Additionally, elevated serum lactate dehydrogenase (LDH) levels—exceeding the upper normal limit by approximately 1.5-fold—correlate with increased tumor burden and reduced survival in advanced melanoma, establishing LDH as a reliable prognostic biomarker [99].
The immunosuppressive nature of the tumor microenvironment (TME) plays a critical role in melanoma progression and therapeutic resistance by orchestrating complex cellular and molecular interactions. Tumor-associated macrophages (TAMs) within the TME secrete cytokines such as interleukin-6 (IL-6) and transforming growth factor-beta (TGF-β), which upregulate vascular endothelial growth factor (VEGF) to promote angiogenesis while simultaneously suppressing CD8+ T-cell effector functions, leading to an immune ‘cold’ tumor phenotype [100]. Additionally, melanoma cells overexpress indoleamine 2,3-dioxygenase (IDO), depleting tryptophan and generating kynurenine, which induces regulatory T-cell (Treg) differentiation and infiltration, further dampening antitumor immunity [101]. Recent studies have shown that melanoma-derived exosomes transfer non-coding RNAs, such as lncRNA Gm26809, to cancer-associated fibroblasts (CAFs), leading to extracellular matrix remodeling and upregulation of ATP-binding cassette (ABC) transporters, thereby contributing to multidrug resistance [102]. Targeting the TME has emerged as a promising therapeutic strategy, with early clinical studies demonstrating the synergistic potential of colony-stimulating factor 1 receptor (CSF-1R) inhibitors for TAM depletion in combination with anti-CTLA-4 antibodies to reinvigorate T-cell responses [103,104].

3.
Foundational biomaterials for wearable bioelectronics
The performance, safety, and clinical viability of any wearable bioelectronic device are fundamentally determined by the materials from which it is constructed. The development of materials that can seamlessly interface with the dynamic, soft, and sensitive environment of human skin is a cornerstone of this field. These materials must not only possess the requisite electrical and mechanical properties but also exhibit excellent biocompatibility to avoid eliciting adverse host responses. This section provides a foundational overview of the key classes of biomaterials that enable the fabrication of advanced wearable devices for skin cancer management.
3.1.
Substrate and encapsulation materials
The substrate serves as the foundational layer of a wearable device, providing mechanical support and flexibility, while encapsulation layers protect the sensitive electronic components from the external environment and shield the skin from direct contact with potentially irritating materials [105]. Polydimethylsiloxane (PDMS), a silicone-based elastomer, is one of the most widely used materials due to its inherent flexibility, established biocompatibility, optical transparency, and gas permeability [106]. Its low Young’s modulus allows it to conform well to the skin’s topography [107,108]. However, despite its general tolerance, individual sensitivities and cases of device rejection have been reported, underscoring the need for rigorous biocompatibility testing [109]. Polyimide is another common substrate, particularly for flexible printed circuits, though its higher stiffness and limited biocompatibility can constrain its use in long-term skin-contact applications [110,111].
To address these limitations, researchers are increasingly turning to naturally derived biomaterials [112–114]. Silk fibroin, a protein extracted from silkworm cocoons, has emerged as a highly promising alternative due to its excellent biocompatibility, biodegradability, and tunable mechanical properties [115]. High-purity silk fibroin has been shown to elicit minimal immune responses, making it well-suited for both wearable and implantable applications [116,117]. Its biodegradability is particularly advantageous for transient electronics or therapeutic devices that are designed to function for a specific period before being safely resorbed by the body.

3.2.
Biocompatible conductive inks and materials
The ability to conduct electrical signals is central to bioelectronics. Creating conductors that are both highly conductive and mechanically compliant is a significant challenge. This has led to the development of various classes of conductive inks and composites designed to bridge the gap between rigid electronics and soft biological tissues. These materials can be broadly categorized into liquid metals, metallic nanoparticle or foil-based conductors, carbon-based materials, and intrinsically conductive polymers.
Gallium-based liquid metal alloys, particularly eutectic galliumindium (EGaIn), have garnered significant attention for their unique combination of metallic conductivity and liquid-state fluidity at room temperature [118,119]. Unlike toxic mercury, Ga-based alloys exhibit excellent biocompatibility and low vapor pressure, making them safe for skin-contact applications [120,121]. Their liquid nature allows them to be injected into microfluidic channels or directly printed onto substrates, forming highly stretchable and self-healing conductive traces that maintain electrical integrity even under significant mechanical strain [122].
Inks formulated with metallic nanoparticles, most notably silver nanowires (AgNWs), offer a pathway to creating highly conductive patterns through simple printing processes [123,124]. After printing, a sintering step (thermal or photonic) fuses the nanowires, forming a percolated conductive network [125]. While AgNWs provide excellent conductivity and flexibility, concerns remain regarding their long-term stability and potential toxicity due to the leaching of cytotoxic silver ions upon oxidation or degradation [126].
Conductive inks based on carbon nanomaterials, such as graphite and carbon nanotubes (CNTs), present a cost-effective and versatile alternative [127]. These materials offer high surface area, which is advantageous for electrochemical sensing, and can be formulated into inks for screen or inkjet printing. However, the biocompatibility of CNTs is a subject of ongoing debate, with studies indicating that factors like length, purity, and functionalization can influence their cytotoxicity and potential to induce inflammatory responses [128,129].
Intrinsically conductive polymers, such as poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS), offer a compelling combination of moderate conductivity, mechanical flexibility, and inherent biocompatibility [130]. PEDOT:PSS can be processed from aqueous solutions, making it suitable for various printing techniques and for creating transparent conductive films. It is frequently used as an electrode material in electrochemical biosensors and as a coating to improve the biocompatibility of other conductors [131,132].

3.3.
Functional hydrogels for the bio-interface
Perhaps the most critical component for achieving a seamless and functional connection between a device and the skin is the bio-interface layer. The microscopic air gaps and mechanical mismatch at this interface represent a central bottleneck that can impede signal quality and device performance [133]. Functional hydrogels have emerged as a transformative solution to this challenge [134,135].
Hydrogels are three-dimensional networks of hydrophilic polymers that can absorb and retain large amounts of water, giving them mechanical properties (e.g., softness, viscoelasticity) that closely resemble those of biological tissues [136]. This tissue-like nature allows them to form an ideal, quasi-solid interface that fills microscopic skin crevices, ensures conformal contact, and minimizes irritation [137,138]. As highlighted by Lim et al., ultrathin, functionalized hydrogels based on poly(acrylamide) (PAAm) can be engineered to be not only ultrasoft but also highly mass-permeable and ionically conductive [139]. This combination of properties is critical: mass permeability allows for the efficient transport of target analytes (e.g., biomarkers from sweat or interstitial fluid) to the sensor surface, while low impedance ensures high-fidelity recording of electrophysiological signals and efficient delivery of electrical stimulation [140].
Furthermore, hydrogels can be designed to be “smart” or stimuliresponsive [141,142]. By incorporating chemical moieties that respond to specific environmental cues such as pH, temperature, light, or enzymes, these hydrogels can undergo controlled changes in their structure, such as swelling or degrading on demand [143]. This capability is particularly valuable for therapeutic applications, enabling the development of wearable platforms that can release drugs in a controlled, localized, and triggered manner.

4.
Wearable bioelectronics for skin cancer screening
Melanoma is the most lethal form of skin cancer, characterized by rapid progression and subtle early-stage symptoms, which pose significant diagnostic challenges [85]. Conventional diagnostic methods often rely on invasive biopsies or specialized clinical imaging techniques [11]. Wearable bioelectronic devices present a promising alternative, utilizing flexible, skin-conformal designs for non-invasive, real-time monitoring of melanoma-specific biomarkers and physiological changes. These technologies leverage a diverse array of biomechanical, biochemical, optical, and molecular markers—including tissue stiffness, tyrosinase levels, refractive index changes, and circulating microRNAs (miRNAs)—to enable early detection and longitudinal monitoring of melanoma. These devices can be categorized into optical sensing devices and electrochemical sensing devices according to the detection principle, and the specific applications of these two devices in skin cancer detection are described below. By integrating advanced materials such as PDMS, polyimide, and hybrid hydrogels with cutting-edge sensing modalities, these devices offer a patient-centric approach that bridges the gap between clinical accuracy and at-home accessibility, holding the potential to revolutionize melanoma diagnostics.
4.1.
Optical sensing devices
Optical sensing wearable bioelectronics operates on the principle that the light-tissue and light-molecule interactions is altered by pathological changes. These devices can transduce the subtle optical shifts caused by pathological transformations into a measurable signal [144, 145]. They typically comprise three essential components: a light source (e.g., LED) to illuminate the skin, a biorecognition element that interacts with the target analyte, and a photodetector that quantifies the resulting changes in optical properties such as intensity, wavelength, or polarization (Fig. 3). The primary mechanisms include absorption spectroscopy, where changes in chromophore concentration (e.g., melanin, hemoglobin) affect the intensity of transmitted or reflected light at specific wavelengths [146–148]; Raman spectroscopy, which detects the inelastic scattering of photons to provide a unique vibrational fingerprint of molecular composition [149,150]; terahertz (THz) spectroscopy, which leverages the high sensitivity of THz waves to water content to differentiate between healthy and cancerous tissue based on hydration levels [151]; and colorimetric methods, which rely on analyte-induced color changes in a chemical reagent, providing a simple, visual readout [152,153]. The intimate and conformal contact afforded by the optical sensing wearable bioelectronics is particularly advantageous for skin cancer detection. It ensures efficient optical coupling to the superficial skin layers—where early-stage lesions typically reside—enabling robust light delivery and detection, which maximizes the signal-to-noise ratio while minimizing interference. Building on these foundational principles, recent research has yielded a variety of innovative wearable platforms tailored for skin cancer diagnostics, as exemplified by the following studies.
Near-infrared (NIR) spectroscopy has emerged as a research hotspot in non-invasive skin cancer detection [154]. Wang et al. developed an active near-infrared spectroscopy patch (ANIRP) that integrates NIR spectroscopy with an eccentric rotating mass (ERM) actuator on a flexible polyimide substrate [155]. The patch induces mechanical vibrations through the ERM and detects the frequency of the mechanical vibrations by means of a near-infrared light-emitting diode (LED) and a photodetector (PD). As the skin vibrates periodically, the length of the light path between the IR LED and the PD changes periodically, allowing the vibration frequency to be measured. And since the mechanical properties of skin cancer are different from normal skin, the frequency of mechanical vibration is also different. The near-infrared light spectrum allows rapid mapping of skin elasticity, with measurements taking less than 1 s per area. It maintains high spatial sensitivity (<1 mm) across a pressure range of up to 300 kPa and achieves a detection depth of 9 mm with larger actuators. ANIRP has demonstrated exceptional performance in both artificial skin models and human trials, accurately identifying biomechanical anomalies associated with melanoma invasion, thereby advancing real-time, non-invasive diagnostics and continuous monitoring.
Raman spectroscopy enables label-free skin cancer diagnosis by analyzing molecular vibrational characteristics [156,157]. Huang et al. developed a wearable microneedle patch for simultaneous surface-enhanced Raman scattering (SERS) and colorimetric dual-mode detection of tyrosinase (TYR) in human skin, facilitating melanoma screening [158]. The microneedles were surface functionalized with dopamine, whose catechol structure undergoes oxidation in the presence of TYR, which is overexpressed in melanoma. Upon compression into the skin, TYR oxidizes dopamine. After the patch is removed, a solution containing SERS-activated Au@Ag–Pt nanoenzymes functionalized with 4-mercaptophenylboronic acid (4-MPBA) is added to the patch surface. The oxidized form of dopamine is unable to interact with 4-mercaptophenylboronic acid, resulting in a “SERS signaling off” state. Meanwhile, the solution was collected and 3,3′,5,5′-tetramethylbenzidine (TMB) was added, and an excess of the nanoenzymes catalyzed the oxidation of colorless TMB to blue oxidized TMB (oxTMB), thereby enhancing the colorimetric signal. This patch demonstrates a linear response to TYR, with a detection limit as low as 0.01 U/mL and a response time of under 5 min, offering a novel approach for melanoma screening and continuous monitoring in lactate dehydrogenase (LDH)-negative patients.
Colorimetric methods are intuitive and equipment-free, making them ideal for at-home testing [152]. Beyond TYR detection, colorimetric assays have also been applied to melanoma-related RNA detection. Sulaiman et al. developed a hydrogel-coated microneedle array capable of rapidly collecting approximately 6.5 μL of skin interstitial fluid within 2 min for detecting the melanoma recurrence biomarker miR-210, achieving a detection limit of 6 nM [159]. The platform utilizes polypeptide nucleic acid (PNA)-functionalized alginate polymers, featuring a 7-mer PNA sequence covalently linked via photolabile click chemistry for light-triggered release (300–360 nm). The PNA probe demonstrates a 15-fold specificity for complementary DNA-210 over non-complementary DNA-141. This patch enables direct visualization of captured biomarkers and light-triggered PNA:DNA release for trace-level detection, offering a versatile molecular approach that can be adapted for multiplexed miRNA analysis (e.g., miR-21, miR-155) to enhance melanoma specificity.
THz imaging is uniquely advantageous for assessing skin cancer infiltration depth due to its non-ionizing nature and high sensitivity to water content [160]. The underlying principle is that cancerous tissues typically exhibit higher water content compared to healthy tissues, creating a distinct dielectric contrast in the terahertz frequency range. This difference in hydration levels allows THz waves to differentiate between normal and malignant areas, offering a non-invasive method for mapping subsurface anomalies [161]. A practical example of this approach is the wearable patch antenna designed by Angappan et al. for skin tumor detection [162]. This device consists of a flexible microstrip patch antenna fabricated on a PDMS substrate, designed to operate in the 2.45 GHz ISM band. When the antenna is placed over the skin, the presence of a tumor alters the local dielectric environment, which in turn causes measurable variations in the antenna’s performance characteristics. Specifically, tumor detection is achieved by monitoring shifts in the reflection coefficient (S11 parameter) and changes in the local electric field (E-field), magnetic field (H-field), and surface current density (J-surf). The antenna, measuring 40 × 40 × 1 mm3, was validated using multi-layered skin phantoms and demonstrated the ability to detect tumors of various sizes while maintaining a Specific Absorption Rate (SAR) of 1.3846 W/kg, safely below the FCC regulatory limit. However, despite the promise of such technologies, their broader clinical adoption remains challenged by the potential cost and complexity of the associated hardware needed for signal generation and analysis.
UV exposure is a major risk factor for skin cancer, making UV monitoring crucial for prevention [86]. Kim et al. introduced a battery-free, stretchable optoelectronic system for wireless skin optical characterization, incorporating UV dosimetry [163]. This device features a UV-responsive dye coating on a thin silicone elastomer substrate, which transitions from blue to transparent upon UV exposure, reaching complete decoloration at approximately 8 J/cm2. Color changes are detected using a red LED (640 nm) and an infrared LED (950 nm), with the latter serving as a reference. The UV dose is calculated from the ratio of infrared to visible signals, enhancing robustness against external interference. The system is powered via Near-field communication (NFC) and is compatible with standard smartphones and tablets, enabling real-time monitoring and alerting users when critical exposure thresholds are reached. Hua et al. developed a skin-inspired, highly stretchable, conformal matrix network (SCMN) that integrates multiple sensing functions, including UV detection for skin cancer prevention [164]. This ZnO-based optical sensor detects 355 nm UV light with a responsivity of 0.738 A/W, a response time of 41 ms at 5 V, and exhibits a linear increase in photogenerated current with UV intensity. This multifunctional e-skin monitors temperature, strain, humidity, magnetic fields, and pressure, ensuring minimal cross-interference and contributing to skin cancer prevention.
Overall, these optical sensing devices create a synergistic toolkit that spans biomechanical, biochemical, optical, and molecular domains, paving the way for a comprehensive wearable platform for skin cancer detection. The major advantage of optical methods is their non-invasive nature and ability to probe tissue at various depths, particularly in the NIR window, making them well-suited for detecting subsurface abnormalities. However, optical sensing is susceptible to several limitations. High inter- and intra-patient variability in skin pigmentation and thickness can significantly affect light scattering and absorption, making it difficult to establish a universal baseline. The limited spatial resolution of some optical techniques can make it difficult to resolve fine details or distinguish between adjacent micro-lesions. Furthermore, the non-specific binding of biomolecules to the sensing surface can lead to false positives, and the high cost and bulk of some optical components can be a barrier to the development of low-cost, disposable devices.

4.2.
Electrochemical sensing devices
Electrochemical sensing wearable bioelectronics have emerged as a transformative approach for non-invasive cancer detection, harnessing advances in materials science and bioelectronics to directly monitor cancer biomarkers [165–170]. These devices transduces a biochemical event into a measurable electrical signal (e.g., current, potential, or impedance), detecting melanoma-specific markers, such as tyrosinase (TYR) and offering high sensitivity and specificity for early cancer screening (Fig. 4a). These sensors typically consist of a three-electrode system—a working electrode, a reference electrode, and a counter electrode—that is in direct contact with the skin or an interstitial fluid-extracting medium. The key mechanisms include amperometry, which measures the Faradaic current generated from the direct oxidation or reduction of a target analyte as a constant potential is applied to the working electrode, with the resulting current being directly proportional to the analyte’s concentration [171,172]. In voltammetry, the applied potential is systematically varied over time (e.g., scanned linearly or cyclically), and the resulting current is plotted against the potential [173,174]. This voltammogram provides qualitative information from the peak potential (identifying the analyte) and quantitative data from the peak current magnitude. Potentiometry is a zero-current technique that measures the potential difference that develops across an ion-selective membrane. This potential, governed by the Nernst equation, is logarithmically proportional to the activity (concentration) of a specific target ion (e.g., H+ for pH, Na+), offering high selectivity [175,176]. Lastly, electrochemical impedance spectroscopy (EIS), which measures the opposition to the flow of an alternating current as a function of frequency, providing information about the electrical properties of the tissue [177,178]. Building on these foundational principles, researchers have developed innovative wearable devices that exemplify the potential of electrochemical sensing for real-time diagnostics.
Amperometric and voltammetric techniques, which quantify analytes by measuring the current generated from redox reactions, are among the most widely adopted strategies in wearable biosensing [166]. The wearable bandage and microneedle sensors developed by Ciui et al. represent a direct amperometric approach for detecting the melanoma biomarker tyrosinase (TYR) [179]. The core of this system is an enzymatic reaction where TYR oxidizes its substrate, catechol (CAT), into benzoquinone (BQ). This BQ product is then electrochemically reduced at a printed carbon working electrode with an applied potential of −0.25 V (vs. Ag/AgCl), generating a measurable current proportional to the TYR level (Fig. 4b). The platform was realized in two distinct formats: a flexible epidermal bandage and a minimally invasive microneedle array. The bandage sensor was fabricated by screen-printing stress-enduring carbon and Ag/AgCl inks onto a standard adhesive bandage, ensuring mechanical resiliency during movement. The microneedle device, designed to access deeper tissues, consists of a hollow polymer array packed with a CAT-coated carbon paste. A key feature of this work is the full integration with a flexible, ultralight electronic board that provides wireless data transmission via Bluetooth Low Energy (BLE) to a mobile device, creating a complete, portable system for melanoma screening.
In a similar effort targeting TYR, Poursharifi et al. designed a sophisticated wearable bioelectronic patch featuring a microneedle array integrated with a surface-bound, chemo-responsive smart probe [180]. Unlike systems using a free substrate, this platform covalently modifies the electrode surface with L-3,4-dihydroxyphenylalanine (l-dopa), which acts as the TYR-responsive probe (Fig. 4c). TYR present in the tissue catalyzes the oxidation of the surface-bound l-dopa to dopaquinone, a reaction that is monitored using sensitive square-wave voltammetry (SWV). The microneedles themselves are fabricated from a composite of polyurethane (PU) and the conductive polymer PEDOT: PSS, a combination that enhances the mechanical robustness and flexibility of the array while maintaining high electrical conductivity. A significant advantage of this design is the electrochemical regenerability of the sensor surface; the reacted dopaquinone can be electrochemically reduced back to its original l-dopa form, mitigating biofouling and extending the sensor’s operational lifespan for continuous monitoring. Validated on ex vivo human skin models, the sensor demonstrated a very low limit of detection (0.06 mg/mL) and high reproducibility.
Offering a different strategy that decouples sample collection from analysis, Darvishi et al. developed a non-invasive method combining tape-stripping with high-resolution electrochemical imaging [181]. In this approach, an adhesive tape is first used to painlessly collect cells from the stratum corneum of a suspicious skin area. This process also sufficiently damages the cell membranes to allow access to intracellular biomarkers without requiring chemical lysing agents. The tape, now containing the collected cells, is analyzed ex situ using scanning electrochemical microscopy (SECM) (Fig. 4d). The detection of TYR is achieved with an immunoassay wherein a primary antibody targets TYR and a secondary antibody, labeled with the enzyme horseradish peroxidase (HRP), provides the electrochemical signal. The HRP label catalyzes the oxidation of a redox mediator (ferrocenemethanol) in the presence of hydrogen peroxide, and this product is then detected by a soft microelectrode probe that is gently brushed over the tape, creating a micrometric map of TYR activity. This technique was successfully used to monitor increasing TYR levels corresponding to melanoma progression in mouse models, demonstrating its potential for staging and rapid point-of-care diagnosis.
Beyond current-based measurements, potentiometric and impedance-based methods offer alternative and highly sensitive routes for biomarker quantification. A prime example of potentiometric sensing is the flexible bio-FET (field-effect transistor) designed by Ren et al. for ultra-sensitive tyrosinase detection [182]. This device operates by measuring changes in electrical potential rather than current. The gate surface of the transistor is functionalized with a self-assembling nanostructured tetrapeptide (tryptophan-valine-phenylalanine-tyrosine, or WVFY) (Fig. 4e). The terminal tyrosine residue on this peptide serves as a substrate for the target TYR enzyme. When TYR is present, it oxidizes the peptide’s phenolic hydroxyl groups, a reaction that consumes protons and thereby alters the net charge and surface potential at the transistor’s gate. This change in gate potential directly modulates the conductivity of the underlying indium oxide semiconductor channel, resulting in a measurable positive shift of the transistor’s threshold voltage (Vth). Due to the inherent signal amplification of the transistor architecture, this method achieves an exceptionally low limit of detection of 1.9 fM. The entire device is fabricated on an ultrathin (~2.9 μm) flexible polyimide substrate, allowing it to conform seamlessly to skin for wearable applications.
Shifting from biomarker detection to tissue characterization, Lee et al. proposed a novel approach for skin cancer diagnosis using electrical impedance tomography (EIT) coupled with graphene electronic tattoos (GETs) [183]. This method leverages the principle that malignant skin lesions exhibit different electrical impedance compared to healthy tissue. The system employs a circular array of ultra-thin, flexible GETs that adhere conformally to the skin around a lesion. GETs are ideal for this application due to their biocompatibility and extremely low skin-electrode interface impedance, which is crucial for high-fidelity measurements. To perform a measurement, a low-frequency current is injected through one pair of electrodes, and the resulting voltages are measured across the remaining pairs. A key innovation is the use of a difference-based imaging protocol, where measurements from the suspicious lesion are contrasted with a baseline taken from a healthy contralateral skin site on the same individual. This self-referencing minimizes the impact of inter-individual variability in skin properties. The collected data are then used to reconstruct a 2D image map of the tissue’s conductivity, providing clinicians with a visual tool to assess lesion malignancy based on its size, position, and impedance profile.
Overall, electrochemical sensors offer several key advantages, including high sensitivity and selectivity, especially when functionalized with enzymes or antibodies, and the potential for miniaturization and low-cost mass production. However, they also face significant challenges. The stability of the biorecognition element (e.g., an enzyme) can be a major issue, as enzymes can degrade over time or be affected by changes in temperature and pH. Biofouling, the non-specific adsorption of proteins and other biomolecules onto the electrode surface, can passivate the sensor and reduce its sensitivity. Moreover, the extraction of biomarkers from the skin in a reliable and reproducible manner remains a significant hurdle, and the direct contact with the skin can sometimes lead to irritation or an inflammatory response.
In comparing these sensing modality, optical sensing is generally better for non-invasive structural and morphological analysis of tissue, while electrochemical sensors excel at the specific and quantitative detection of molecular biomarkers. The choice between them, therefore, depends on the specific application and the target analyte. For a comprehensive skin cancer diagnostic platform, a multimodal approach that integrates both optical and electrochemical sensing could be particularly powerful, leveraging the strengths of each to provide a more complete and accurate assessment of skin health. To provide a consolidated overview, Table 1 summarizes the key optical and electrochemical sensing platforms discussed, detailing their respective target biomarkers, materials, and reported performance metrics.

5.
Wearable bioelectronics for skin cancer treatment
With the rapid development of wearable devices, the treatment of skin cancer is shifting from traditional systemic interventions to more precise, minimally invasive, and personalized strategies. Wearable therapeutic devices have significantly improved efficacy while reducing systemic side effects by enabling localized energy modulation, targeted drug delivery, and immune microenvironment remodeling. This section systematically discusses the technological advancements and clinical applications of chemotherapy, photodynamic therapy (PDT), electrotherapy, immunotherapy, and combination therapies (Fig. 5).
5.1.
Chemotherapy
Conventional chemotherapeutic agents, such as dacarbazine and cisplatin, face significant limitations in skin cancer treatment due to high systemic toxicity and poor tumor specificity [184–189]. Flexible bioelectronic technologies offer a solution by enabling precise spatiotemporal control of drug delivery through minimally invasive administration systems and intelligent release strategies, thereby enhancing therapeutic efficacy while mitigating adverse effects.
A representative example is the flexible bioelectronic microneedle patch (FBMP) developed by Jin et al. (Fig. 6a) [190]. This device integrates an EGaIn heating film and thermoresponsive bilayer microneedles onto a flexible printed circuit board. Each microneedle consists of a polycaprolactone (PCL) outer shell and a polyvinyl alcohol (PVA) inner core loaded with chemotherapeutic agents, such as proteolysis-targeting chimeras (PROTACs). Wireless control via a smartphone application enables localized heating of the EGaIn film (up to 63 °C), triggering phase transition of the microneedle shell and allowing for tunable drug release profiles: rapid release within 2 min for immediate therapeutic effects or sustained release over 10 h for prolonged treatment. In a melanoma mouse model, FBMP-mediated co-delivery of PROTACs and interferon-gamma (IFN-γ) resulted in significant tumor growth inhibition. Notably, blood analysis showed that compared to intravenous IFN-γ administration, FBMP delivery markedly reduced pro-inflammatory cytokines IL-6 and TNF-α while elevating protective IL-10 levels, effectively mitigating cytokine storm and minimizing systemic toxicity. This thermally modulated precision drug delivery approach positions FBMP as a promising outpatient treatment modality for melanoma.
Furthermore, Chen et al. combined bioorthogonal catalysis with microneedles to develop a bioorthogonal catalytic microneedle patch, enabling safe and efficient prodrug activation (Fig. 6b) [191]. This patch integrates palladium nanoparticles (Pd NPs) with titanium dioxide (TiO2) nanosheets embedded in a biocompatible PVA matrix, where Pd NPs catalyze bioorthogonal reactions to unmask prodrugs and restore their therapeutic activity. Upon systemic administration, N-alloc-pro- tected doxorubicin (alloc-DOX) accumulates at the tumor site, where the patch catalytically activates the prodrug to its cytotoxic form, DOX (Fig. 6c). In a B16F10 melanoma mouse model, this approach demonstrated significantly superior tumor suppression compared to conventional DOX chemotherapy. Moreover, compared to direct microneedle-mediated DOX delivery, bioorthogonal catalytic microneedle treatment resulted in higher intratumoral DOX concentrations while minimizing off-target exposure in normal tissues, thereby reducing systemic toxicity and making it more suitable for long-term and multi-cycle therapy.

5.2.
Photodynamic therapy
PDT is a non-invasive and effective approach for skin cancer treatment, leveraging photosensitizers that generate reactive oxygen species (ROS) upon exposure to specific wavelengths of light to selectively destroy tumor cells while preserving surrounding healthy tissue [192–196]. However, conventional PDT is constrained by the need for controlled light exposure and clinical administration, requiring patients to visit healthcare facilities for treatment. This limitation may reduce patient adherence and restrict broader adoption. Moreover, PDT efficacy is hindered by the photobleaching and limited tumor selectivity of photosensitizers. To address these challenges, recent advances in wearable PDT devices have enabled consistent and on-demand light exposure outside clinical settings, offering a more convenient, patient-friendly, and effective therapeutic solution.
To facilitate wearable PDT, Jeon et al. developed a parallel-stacked organic light-emitting diode (PAOLED) system (Fig. 6d), overcoming the challenge of delivering high-intensity light in a compact, skin- conformal format [197]. PAOLED features a novel structure comprising multiple luminescent units stacked in parallel on a flexible polyethylene terephthalate (PET) substrate. These units incorporate organic compounds such as tris(8-hydroxyquinoline) aluminum (Alq3) and N,N′-di(1-naphthyl)-N,N′-diphenyl-(1,1′-biphenyl)-4,4′-diamine (NPB). This design achieves a power density exceeding 100 mW/cm2 under a low driving voltage (<8 V), facilitated by optimized indium tin oxide (ITO) electrodes that enhance charge injection efficiency. The exceptional flexibility of PAOLED ensures seamless integration with the skin, a critical feature for wearable applications. In vitro experiments using B16F10 melanoma cells demonstrated that PAOLED irradiation at 625 nm (matching the absorption peak of porphyrin-based photosensitizers) for 0.5 h increased singlet oxygen generation by 3.8-fold compared to conventional OLEDs, reducing cell viability by 24 %. This rapid and efficient performance positions PAOLED as an ideal platform for at-home PDT, potentially shortening treatment duration and improving patient accessibility.
Addressing the challenges of photosensitizer photobleaching and tumor targeting, Dai et al. introduced a microneedle-based system (Microneedles@AIE PSs) utilizing aggregation-induced emission (AIE) photosensitizers for metronomic PDT (mPDT), which optimizes treatment through sustained, low-intensity light exposure (Fig. 6e) [198]. The microneedles, composed of carboxymethyl cellulose sodium—a biocompatible polymer—are loaded with the AIE photosensitizer PyTPA, which exhibits superior ROS generation efficiency and photostability compared to conventional photosensitizers such as Rose Bengal. This system enables uniform and deep intratumoral delivery of photosensitizers while simultaneously serving as an optical transmission channel for an embedded LED microarray. Additionally, the mPDT system features wireless power transfer, allowing patients greater freedom of movement during therapy. In vivo validation using a B16F10 melanoma mouse model demonstrated significant tumor suppression, with potential applications in reducing tumor recurrence when combined with surgical resection and enhancing efficacy when integrated with immunotherapy. Collectively, this microneedle-based platform not only improves therapeutic outcomes but also reduces side effects, offering a safer alternative to conventional high-intensity PDT.

5.3.
Electrotherapy
Electrotherapy, encompassing techniques such as irreversible electroporation (IRE) and tumor-treating fields (TTFields) for direct tumor ablation, as well as electrochemotherapy (ECT) and electro-dynamic therapy (EDT) for indirect cytotoxicity, has emerged as a promising approach for treating various cancers, including skin malignancies [199–204]. ECT, for instance, utilizes pulsed electric fields to temporarily permeabilize cancer cell membranes, enhancing intracellular drug delivery [205,206]. This strategy not only improves therapeutic efficacy but also minimizes systemic toxicity, offering a compelling alternative to conventional treatments. Historically, these therapies have relied on stationary, clinic-based equipment, limiting patient accessibility and comfort. However, the advent of wearable technologies marks a paradigm shift, enabling continuous, patient-centric, and potentially home-based electrotherapy management. This aligns seamlessly with the broader trend toward personalized medicine. By integrating electrotherapy into wearable platforms, targeted, non-invasive treatment of skin cancer lesions can be achieved, offering advantages such as enhanced patient mobility and real-time therapeutic modulation.
To improve the skin compatibility and electrical performance of TTFields therapy for skin tumors, Li et al. developed wearable electrodes composed of liquid metal alloys EGaIn [207]. These materials remain in a liquid state at room temperature and can be directly spray-coated onto the skin using a templating approach, forming soft, flexible electrodes. The generated low-intensity, intermediate-frequency sinusoidal electric fields (e.g., 300 kHz, 5 V peak-to-peak) disrupt mitotic spindle assembly during cell division, selectively targeting rapidly proliferating cancer cells while sparing quiescent healthy tissues. In a preclinical study using a B16F10 melanoma mouse model, six days of daily field application resulted in complete tumor regression. The skin-conformal nature of these electrodes ensures uniform field distribution over irregular lesion surfaces, while their non-thermal mechanism (temperature increase <0.5 °C) minimizes discomfort and tissue damage. This approach provides a portable, user-friendly alternative to conventional TTFields systems, with the potential to expand the accessibility of this therapy.
Another innovative strategy integrates wearable devices with iontophoresis and biomechanical energy harvesting to enhance trans- dermal drug delivery. Wang et al. developed a self-powered microneedle patch incorporating a flexible triboelectric nanogenerator (F-TENG) (Fig. 6f) [208]. The F-TENG, constructed from layered silicone rubber and conductive fabric, converts mechanical energy from patient movements (e.g., walking or arm swinging) into electricity, generating an open-circuit voltage of up to 482 V and a short-circuit current of 54 μA. By integrating F-TENG with a conductive-layered microneedle patch, they created a self-powered microneedle system (F-MN) for iontophoresis-driven drug delivery. Upon skin insertion, the microneedles dissolve, releasing pH-responsive nanoparticles (Ce6(DOX) @CaCO3-PEG NPs) encapsulating doxorubicin (a topoisomerase inhibitor) and chlorin e6 (a photosensitizer). Under electrical stimulation, these nanoparticles penetrate deeper into the tumor, where they degrade in the acidic tumor microenvironment to release their therapeutic payload. In a deep-seated melanoma mouse model, histological analysis confirmed enhanced intratumoral drug penetration, and mice treated with F-MN exhibited significantly smaller tumor volumes compared to those receiving conventional microneedle therapy. This self-powered design eliminates the need for external batteries, enhancing long-term usability while improving therapeutic efficacy.

5.4.
Immunotherapy
Immunotherapy eradicates tumor cells by delivering immune cells or immunomodulatory agents to activate the body’s immune response [209–214]. While immune cell therapies and immune checkpoint inhibitors (e.g., anti-PD-1 antibodies) have revolutionized skin cancer treatment, systemic administration frequently induces immune-related adverse events (irAEs) such as dermatitis, colitis, and pneumonitis, thereby limiting their therapeutic potential [215–217]. Flexible wearable devices and localized drug delivery systems offer a promising alternative by directly targeting the tumor site and modulating the local immune microenvironment, enabling efficient and low-toxicity immunotherapy.
To achieve precise transdermal delivery of therapeutic cells, Chang et al. developed an innovative cryogenic microneedle patch (cryoMN) (Fig. 6g) [218]. These cryoMNs are fabricated using a cryopreservation medium containing sucrose and dimethyl sulfoxide (DMSO), which stabilizes viable immune cells, such as cytotoxic T cells and mesenchymal stem cells (MSCs), during freezing and thawing. The microneedles feature a sharp conical design with a compressive strength of approximately 24.7 ± 3.8 MPa, ensuring penetration through the stratum corneum without fracture. Upon insertion, the ice matrix melts within 1 min at body temperature, releasing the encapsulated cells into the dermis, where they can directly interact with tumor antigens. In a preclinical melanoma mouse model, cryoMN-delivered dendritic cells (DCs) retained their viability and proliferative capacity even after one month of storage. CryoMN treatment resulted in a threefold increase in mature DCs in the draining lymph nodes compared to controls, significantly enhancing local immune activation, suppressing tumor growth, and minimizing systemic exposure and irAEs.
Similarly, to enhance microdosed immunomodulatory drug delivery, Joo et al. introduced a dissolvable self-locking microneedle (MN) patch with an integrated flexible hydrogel backing (Fig. 6h) [219]. Manufactured using projection micro-stereolithography, these self-locking microneedles feature sharp tips, broad interlocking bodies, and mechanical support, ensuring complete insertion and adhesion even on irregular surfaces such as melanoma lesions. The microneedles were loaded with anti-PD-L1 antibodies (αPD-L1 Ab) and SD-208, a transforming growth factor-beta (TGF-β) inhibitor, enabling the synergistic combination to be directly delivered into the tumor microenvironment. In B16F10 melanoma-bearing mice, this approach outperformed intratumoral injection, achieving superior tumor suppression through enhanced T cell-mediated cytotoxicity and metastasis inhibition while avoiding systemic exposure. The simplicity and scalability of this design underscore its translational potential as a patient-friendly alternative to conventional drug administration routes.
Compared to chemical or biological immune activation, electrical stimulation (ES) offers a versatile and device-efficient approach to augment immunotherapy, though bulky equipment has hindered clinical application. To address this limitation, Pan et al. developed a flexible microneedle array-integrated interdigitated electrode (FMIE) for ES-mediated antitumor immunomodulation [220]. Fabricated using optical 3D microprinting and gold electroless plating, FMIE delivers low-voltage (1 V) ES via polymeric microneedles, inducing immunogenic cell death and releasing damage-associated molecular patterns in B16F10 melanoma models (Fig. 6i). This triggers a robust local and systemic antitumor immune response, significantly reducing both primary and metastatic tumor burdens while minimizing skin damage and systemic toxicity. The portability and biocompatibility of this wearable ES device establish it as a multifunctional platform for next-generation immunotherapy.

5.5.
Combination therapy
Combination therapy integrates multiple therapeutic mechanisms to overcome the limitations of single-modality treatments, offering improved outcomes for complex diseases such as skin cancer [221–229]. Flexible wearable devices have emerged as innovative platforms, enabled precise and integrated therapeutic interventions while preserving patient mobility and comfort. The following examples illustrate how these technologies facilitate combination therapy, enhancing efficacy while maintaining a high quality of life.
Ma et al. introduced a stretchable electronic patch that combines thermotherapy with chemotherapy for postoperative skin cancer management [230]. This skin-adherent device incorporates a composite nano-textile dressing, composed of thermoplastic polyurethane (TPU) nanofibers embedded with lauric acid (LA)/DOX microspheres, interwoven with a liquid-metal heater. Localized heating (up to 55 °C) triggers on-demand drug release, ensuring targeted chemotherapy at the tumor site. The patch’s stretchable design ensures conformal skin contact, maintaining functionality even under mechanical strains such as stretching and bending during daily movements. A key feature is its wireless operation, allowing remote control via a smartphone to precisely adjust drug release kinetics and heating duration. In a melanoma mouse model, this untethered system effectively suppressed tumor recurrence through the synergistic effects of thermal ablation and chemotherapy, reducing relapse risks without interfering with normal activities. The integration of biocompatible materials and skin-adaptive properties positions this patch as a promising non-invasive, patient--friendly cancer care tool.
Ju et al. reported an electrically stimulated photothermal patch (eT-patch) designed to treat melanoma by integrating electrical stimulation and photothermal therapy [231]. This wearable device employs a transparent ionogel doped with MXene (Ti3C2Tx), a two-dimensional nanomaterial that enhances conductivity and photothermal efficiency. Under 808 nm NIR laser irradiation at 0.5 W/cm2, the patch generates controlled heat for tumor cell ablation, while electrical stimulation induces both apoptosis (programmed cell death) and pyroptosis (inflammatory cell death), amplifying therapeutic efficacy. This dual-action mechanism maximizes tumor destruction while minimizing damage to surrounding healthy tissue. The patch’s optical transparency enables real-time monitoring of skin responses during treatment, enhancing precision and safety. In melanoma models, the eT-patch demonstrated significant tumor suppression and reduced side effects, highlighting its potential as a versatile, non-invasive solution for skin cancer therapy.
Tao et al. further expanded on this approach by developing a photothermal/acid-responsive fucoidan-copper sulfide (Fuc-CuS) microneedle patch (BPMN-CuS/DOX) for combined chemodynamic therapy (CDT), photothermal therapy (PTT), and chemotherapy [232]. When embedded sodium bicarbonate encounters an acidic environment, it generates CO2 bubbles, facilitating the rapid dissolution of hyaluronic acid-based microneedles containing Fuc-CuS nanoparticles and doxorubicin, thereby enhancing drug penetration to a depth of 800 μm. This system integrates three therapeutic mechanisms: under 808 nm NIR irradiation, Fuc-CuS NPs elevate temperatures by 24.1 °C for photothermal ablation; Cu2+ ions catalyze a Fenton-like reaction, converting tumor-intrinsic H2O2 into toxic hydroxyl radicals for CDT; and doxorubicin not only directly kills cancer cells but also elevates intracellular H2O2 levels, sustaining treatment efficacy. In B16F10 melanoma models, this triple-combination therapy achieved superior tumor suppression while reducing the doxorubicin dose to 1.38 mg/kg, significantly lowering systemic toxicity.
Yang et al. proposed a silk-based microneedle device (SMND) targeting cancer stem cells (CSCs), integrating immunotherapy (anti-PD-1 antibodies) with hydrogen therapy [233]. This dual-layer microneedle design employs smartphone-controlled temperature modulation to trigger the phase transition of polycaprolactone (PCL) in the outer layer, releasing hydrogen gas derived from ammonia borane (AB) to disrupt CSC oxidative balance. Meanwhile, the inner layer, composed of ethanol-treated silk fibroin (SF), enables the sustained release of anti-PD-1 to block immune evasion, promoting CD8+ T-cell infiltration within tumors. This spatiotemporally controlled combination strategy achieved efficient CSC eradication and tumor suppression in B16F10-CSC melanoma models while avoiding systemic side effects.
Wearable bioelectronics offer a paradigm shift from systemic to localized treatment, which is their principal advantage. Drug-delivery platforms, whether for chemotherapy or immunotherapy, utilize microneedle-based systems to precisely release therapeutic agents like PROTACs, prodrugs, or anti-PD-L1 antibodies directly into the tumor microenvironment. This approach dramatically reduces the systemic toxicity and immune-related adverse events associated with conventional administration routes. However, these systems are often constrained by a finite drug payload and the stability of the loaded biologic agent, such as the viability of immune cells in cryo-microneedles. Conversely, energy-based therapies such as photodynamic therapy and electrotherapy provide on-demand, non-chemical treatment by delivering physical stimuli like light or electrical fields. Wearable platforms like parallel-stacked OLEDs for PDT or liquid metal electrodes for TTFields enable convenient, home-based care that was previously reliant on bulky clinical equipment. The primary limitations for these modalities are the physical constraints of energy delivery; for instance, the efficacy of PDT is limited by the penetration depth of light into tissue, while electrotherapies depend on a continuous power supply—a challenge that self-powered systems based on TENGs are beginning to address. Combination therapies, which integrate multiple strategies like chemo-photothermal systems, represent the most powerful approach, achieving synergistic tumor suppression that monotherapies cannot. Ultimately, while each of these wearable platforms offers the crucial advantage of localized treatment, their specific strengths and limi- tations—such as payload capacity versus power requirements—vary by modality. A detailed comparison of these approaches is provided in Table 2.

6.
Feasibility and safety
Wearable bioelectronics hold great promise for melanoma diagnosis and treatment. However, their clinical translation requires a systematic evaluation of both technological feasibility—such as device integration and mechanical adaptability—and long-term safety, including biocompatibility and material degradation risks. This section provides a comprehensive analysis of wearable electronics for melanoma applications, focusing on integration strategies, mechanical performance optimization, and biocompatibility considerations to ensure clinical viability.
6.1.
Device integration: self-powered systems, miniaturization, and wireless connectivity
The integration of wearable electronic devices is a key driver of their clinical application, encompassing three core modules: energy supply, hardware miniaturization, and data interaction. Traditional bioelectronic devices typically rely on batteries as external energy sources; however, batteries are prone to corrosion, can release toxic heavy metal ions, and often contribute to bulky and rigid device architectures. In contrast, self-powered systems that harvest ambient energy offer a compelling alternative. Triboelectric nanogenerators (TENGs) convert mechanical energy from body motion into electricity through contact electrification, typically producing high voltage outputs suitable for low-power sensors [234–238]. Piezoelectric nanogenerators (PENGs) function via the piezoelectric effect, converting mechanical stress into an electrical signal, and are particularly effective for pressure or strain sensing [239–241]. Magnetoelastic generators (MEG) harness the giant magnetoelastic effect, whose principle involves a mechanical deformation-induced magnetic flux variation. [242]. TENGs and PENGs are effective at converting low-frequency mechanical movements into electricity, while MEGs demonstrate superior performance in moist environments like heavy perspiration. This property opens new possibilities for sweat-resistant device designs, particularly for applications integrating microneedle-based biofluid extraction. Both these systems convert environmental energy—such as motion or pressure from the human body—into electricity, achieving high energy conversion efficiencies. They can generate volt-level output and current in the milliampere range, making them well-suited to power low-energy medical sensors and wearable health-monitoring devices while enabling more compact, lightweight designs [36,37,243–246]. For instance, Zhang et al. developed a photovoltaic charging textile that integrates photovoltaic fibers with Zn/MnO2 fabric batteries (Fig. 7a) [247]. This system requires only 1 min of sunlight exposure to sustain a wearable sensor network for 10 min (0.1 mA output) and maintains energy storage stability for 60 days under extreme conditions such as twisting and immersion. Scalable industrial weaving processes enable mass production, and its lightweight design (<2.8 mg/cm2) combined with cotton-like softness makes it particularly suitable for wearable energy storage. These novel self-powered technologies provide a sustainable energy solution for dynamic skin cancer monitoring.
Miniaturization relies on advances in micro/nanofabrication [248–254]. Lithography-assisted transfer printing can reduce sensor sizes to sub-millimeter scales [255–258]. Park et al. introduced an ultra-flexible organic photovoltaic–electrochemical transistor integration system with a thickness of only 3 μm and a weight of 36.6 μg (Fig. 7b) [259,260]. Using DVD-template nanograting patterning (760 nm periodicity), the system achieves a high-power conversion efficiency of 10.5 %, leading to a highly integrated and miniaturized flexible bioelectronic device. Its adaptability to dual-curvature deformation (200 % stretchability) allows seamless attachment to complex skin topographies, and when adhered to the heart’s surface, it successfully recorded electrocardiogram signals with a signal-to-noise ratio (SNR) of 40 dB. While this device has not yet been applied to melanoma detection, its design principles provide valuable insights for developing non-invasive melanoma screening technologies with high sensitivity and miniaturization.
Wireless remote control is essential for closed-loop diagnostic and therapeutic systems [261–267]. With the rapid advancement of the Internet of Things (IoT), NFC and Bluetooth Low Energy (BLE) technologies have become widely adopted for data transmission in wearable devices (Fig. 7c) [268]. Ciui et al. developed two wearable tyrosinase sensors for melanoma screening in the form of a flexible bandage and a microneedle array [179]. These sensors interface with a wearable electronic board equipped with BLE, enabling real-time data transmission to smartphones and computers. As discussed in a recent review by Zhao et al., advanced wireless strategies, including passive tag systems, NFC, and Bluetooth, have significantly enhanced data transmission efficiency and accessibility [269]. These approaches not only facilitate real-time melanoma detection but also establish a foundation for remote-controlled therapeutic interventions, such as targeted phototherapy, thereby advancing personalized skin cancer management.
The combined innovations in self-powered system, miniaturization, and wireless connectivity are propelling flexible bioelectronics toward clinical applications, offering precise and patient-centric solutions for the diagnosis and treatment of skin cancer.

6.2.
Mechanical performance: adaptability and motion artifact suppression
The successful application of flexible bioelectronic devices in skin cancer diagnosis and treatment largely depends on their mechanical performance. These devices must seamlessly integrate with the dynamic skin surface, maintain stable signal acquisition, and minimize motion artifacts. Key requirements include high stretchability, bending stability, and reliable skin adhesion.
High stretchability is critical for devices to conform to skin deformation during motion. A stretchable ultrasonic transducer array demonstrates this capability using an “island-bridge” architecture (Fig. 7d) [270]. This design combines rigid piezoelectric components with flexible silicone elastomer films, achieving over 50 % stretchability. The low modulus of silicone (~70 kPa) and the high stretchability of the top and bottom layers (~900 %) promote skin conformity during motion. The “island-bridge” design effectively isolates active components from mechanical strain by connecting them to flexible bridges, ensuring that the active components remain unaffected by skin deformation.
In addition to stretchability, wearable bioelectronic devices also undergo bending and torsional stresses. Organic thermoelectric fibers made from PEDOT:PSS exhibit excellent bending stability, maintaining a stable voltage output even after 200 bending cycles (Fig. 7e) [271]. These fibers, produced through freeze-thaw-induced gelation and wet spinning processes, have high conductivity and thermoelectric performance, making them suitable for flexible wearable devices.
Reliable skin adhesion is essential for minimizing motion artifacts. Permanent fluid magnets (PFM) offer a new approach to achieving highly conformable skin adhesion in liquid bioelectronics [59,272,273]. PFMs are generated by stabilizing non-Brownian magnetic nanoparticles in a fluid, providing high magnetization and flowability, allowing them to adapt to complex skin topographies. The alginate solution base of PFM facilitates seamless interface formation with the skin, which is crucial for dynamic cardiac monitoring without motion artifacts (Fig. 7f) [59].
For long time and comfortable wearing, dynamic control of adhesion is important to reduce skin irritation. Thermoresponsive polymers such as poly(N-isopropylacrylamide) (PNIPAM) provide an on-demand detachment solution. PNIPAM changes its wettability properties above and below its lower critical solution temperature (~32 °C), making it suitable for controlling adhesion [274]. Polyurethane-urea bioadhesives demonstrate strong adhesion at body temperature (37 °C) and ease of detachment at lower temperatures (10 ° C), showcasing the potential of thermoresponsive materials for wearable sensors [275]. Another strategy involves breathable bioelectronics that incorporate microchannels to leverage Laplace pressure, enabling efficient sweat transport to the device surface and thereby reducing sweat accumulation and the risk of skin inflammation [276].
Motion artifacts remain a significant challenge [277–281]. Hardware solutions like the “island-bridge“ configuration effectively decouple active components from mechanical deformations, reducing interference. This design minimizes stress at the device-skin interface during motion. Algorithmic processing further mitigates motion artifacts. Techniques like Kalman filters and Convolutional Neural Networks (CNN) are used to correct noise caused by movement in real-time. Kalman filters adaptively estimate and remove noise, often using data from auxiliary sensors like accelerometers. On the other hand, CNNs can learn complex artifact patterns and effectively suppress motion artifacts in physiological signals. Both hardware and algorithmic strategies are important in managing motion artifacts in soft bioelectronics.
Advances in materials science and engineering have made it possible to develop flexible bioelectronics with customizable mechanical properties for skin cancer applications [282]. Novel materials such as the “island-bridge” architecture, PEDOT:PSS, and permanent fluid magnets, along with dynamic adhesion mechanisms, are critical for seamless integration with the skin. Furthermore, the combination of hardware design and complex algorithmic processing is essential for effectively managing motion artifacts, paving the way for reliable and accurate wearable bioelectronics for diagnosis and treatment.

6.3.
Biocompatibility: degradation and host immune response
To fully realize the potential of flexible bioelectronic devices in skin cancer applications, including diagnosis, continuous monitoring, and targeted therapy, a thorough understanding of their biocompatibility and safety is essential. These devices are designed for close contact with the skin, often for extended periods. Due to the presence of cancerous tissue, the skin’s barrier function may be compromised, and immune responses may change [283,284] (Fig. 7g). The interaction between a device and the host immune system is often described as the foreign body response (FBR) [285,286]. This process begins with the adsorption of host proteins onto the device surface, followed by the recruitment of immune cells like macrophages. If the material is perceived as a persistent threat, this can lead to chronic inflammation, the formation of a fibrous capsule around the device, and ultimately, device failure [287–289]. Therefore, material selection and device design must be carefully considered. A comprehensive assessment of potential adverse reactions, ranging from localized irritation to systemic immune effects, is necessary to ensure patient safety and therapeutic efficacy.
One commonly used material in flexible bioelectronics is medical-grade PDMS, known for its inherent flexibility, established biocompatibility, and permeability in various medical devices [106,290,291]. Despite its generally good tolerance, cases of device rejection have been reported, indicating individual sensitivity [109]. Thus, while PDMS offers many advantages, a thorough biocompatibility evaluation (in compliance with standards like ISO 10993) is crucial for its safe implementation in skin cancer-related devices. Silk fibroin, a natural protein derived from silkworms, is another promising material for flexible bioelectronics, gaining attention due to its biodegradability and inherent biocompatibility [292]. Studies have shown that high-purity silk fibroin, produced through careful manufacturing processes, minimizes significant immune responses, making it suitable for tissue engineering applications [293,294]. Therefore, to safely and effectively use silk fibroin in skin cancer therapy, high-purity materials and rigorous skin contact testing protocols are essential to minimize the risk of adverse immune reactions.
A key safety concern for wearable bioelectronics, particularly for long-term use, is the potential release of microplastics when polymer components degrade (Fig. 7h). Polyurethane, commonly used in flexible devices, can undergo photo-oxidation when exposed to UV radiation, leading to the release of dissolved organic carbon and smaller polymer fragments [295–297]. Long-term exposure to microplastics released from wearable devices raises concerns about potential chronic inflammation in the skin. To address this, researchers are exploring the use of inherently biodegradable polymers, such as poly(lactic-co-glycolic acid) (PLGA), in wearable electronics [298,299]. PLGA, with biocompatibility and biodegradability, has FDA approval for various medical applications and offers adjustable degradation rates and mechanical properties. Another promising strategy is integrating self-healing materials, such as those based on Diels-Alder dynamic covalent networks, into flexible bioelectronic devices [300]. These materials have the ability to autonomously repair physical damage, potentially preventing the formation and release of microplastic particles by sealing cracks and maintaining structural integrity.
Many flexible bioelectronic devices rely on metal components (including gold, platinum, and silver nanowires) to achieve the necessary conductivity. However, the possibility of electrochemical corrosion and the subsequent release of metal ions into surrounding tissues presents significant biocompatibility concerns (Fig. 7i). Gold and platinum exhibit strong corrosion resistance in biological environments, leading to minimal ion release, making them suitable for long-term implanted electrodes. Platinum, in particular, is favored for its chemical stability and minimal reactivity in vivo. While silver nanowires offer excellent conductivity and flexibility, concerns remain about their potential to oxidize and release cytotoxic silver ions. Studies have shown that silver nanowires exhibit dose- and time-dependent toxicity in various cell types, with shorter and finer nanowires generally exhibiting higher cytotoxicity [301]. To mitigate the risks associated with metal ion release, atomic layer deposition (ALD) is being explored as an electrical method to apply ultra-thin conformal coatings (such as aluminum oxide, Al2O3) to metal components. These coatings can serve as effective barriers, preventing corrosion and reducing the potential release of harmful ions [302]. A more comprehensive strategy is to use non-metal conductors, such as PEDOT:PSS conductive polymers, which combine good conductivity, inherent biocompatibility, and flexibility, making them an attractive alternative to traditional metal conductors.
A long-standing challenge in wearable bioelectronics is biofouling, the unwanted accumulation of proteins, cells, and microorganisms on device surfaces, which can hinder performance and reduce device lifespan. To address this, researchers are exploring various anti-fouling strategies. Zwitterionic polymers, such as poly(sulfo betaine), show significant efficacy in resisting non-specific protein adsorption due to their strong hydration layer [303]. Experimental data on the use of zwitterionic peptide hydrogels in electrochemical biosensors indicate their effectiveness in preventing protein fouling, enabling reliable detection of target analytes in complex biological samples [304]. Another promising approach is using biomimetic phospholipid coatings, inspired by the anti-fouling properties of natural cell membranes. These coatings form a hydrated layer that serves as a protective barrier, minimizing the adsorption of harmful substances. For example, conductive biomimetic coatings containing phospholipids have demonstrated good low-protein adsorption properties in challenging biological matrices [305].
In summary, the successful development and clinical translation of flexible bioelectronic devices for skin cancer applications rely on a comprehensive understanding and careful management of biocompatibility and safety. This requires careful material selection, thorough evaluation of potential risks such as allergies, microplastic release, electrochemical corrosion, and biofouling, and the implementation of appropriate mitigation strategies. By leveraging advancements in materials science, including the use of biocompatible polymers, protective coatings like ALD, and anti-fouling strategies involving zwitterionic polymers and phospholipid coatings, the field can move toward creating safe and effective flexible bioelectronic devices for the diagnosis, monitoring, and treatment of skin cancer.

7.
Challenges and prospects
Despite the immense potential of flexible bioelectronics in the diagnosis and treatment of cutaneous melanoma, their full clinical translation faces multiple technological, clinical, and ethical challenges. This section systematically analyzes current bottlenecks and outlines future directions based on recent advancements.
7.1.
Technological bottlenecks and clinical translation challenges
The long-term reliability of materials and devices remains a key challenge in flexible bioelectronics. While PDMS is widely used due to its biocompatibility and ease of fabrication, its in vivo performance is complex. Solid PDMS is hydrophobic and does not easily swell in aqueous environments, althou gh certain organic solvents can cause swelling. It has been shown that degradation products linear low molecular weight PDMS can be detected on the surface of PDMS after 1 month of implantation [306]. And as the implantation time continues to increase, the morphology and mechanical properties of PDMS change significantly, highlighting the need for further investigation into systems intended for implantation beyond one year.
Energy sustainability also presents a major limitation for wearable bioelectronics, particularly for therapeutic devices. Self-powered systems, including TENGs, PENGs, MEGs and biofuel cells (BFCs), offer promising solutions to harness mechanical energy or physiological fuel [19,243,244,246]. TENGs have demonstrated output power in the milliwatt range; however, the typical energy density may be insufficient for high-power applications like laser ablation or electrotherapy. Similarly, the degradation of enzyme catalysts can hinder the longevity of BFCs, even though stabilization strategies may moderately extend the enzyme’s half-life. Advances are required to improve energy density and lifespan to meet the demands of energy-intensive therapies.
Integrating and interpreting data from different sensor modalities further complicates the development of smart wearable systems for skin cancer diagnosis and therapy. Wearable devices may combine optical and electrochemical sensors, each with different spatial and temporal resolutions, posing challenges for developing robust cross-modal algorithms. While multimodal data fusion has improved cancer diagnosis when combining imaging with clinical data, applying these technologies to noisy and heterogeneous wearable sensor data is not straightforward. Although advanced AI models, such as Transformers and graph neural networks, have achieved high accuracy in dermoscopic image diagnostics [307], their application to complex physiological signals captured by wearable devices remains an unresolved challenge, particularly considering the significant computational demands of such models.
In addition to technical issues, the clinical application of wearable bioelectronics in skin cancer must address concerns related to biocompatibility, cost-effectiveness, and user acceptance. Medical-grade PDMS and silk fibroin have demonstrated good biosafety in vitro and in short-term animal studies; however, comprehensive long-term evaluations in humans are still needed. Furthermore, the manufacturing cost of flexible devices, especially those incorporating advanced optical sensors, remains high. Although these devices have the potential for low-cost, real-time diagnosis when combined with AI-driven analytics, their adoption in resource-limited settings may be restricted. Lastly, the familiarity of clinicians with wearable electronics and patient concerns regarding comfort and aesthetics are key factors influencing their acceptance.
Overall, while significant progress has been made in the development of flexible bioelectronic devices for skin cancer, addressing these challenges is crucial for their successful clinical implementation. Advances in material durability, energy sustainability, data integration, and addressing both cost and user acceptance will be vital to ensuring that these technologies can provide effective, accessible solutions for skin cancer diagnosis, monitoring, and treatment.

7.2.
Future directions and innovative strategies
Material innovation is crucial to overcoming the technical limitations faced by flexible bioelectronics, particularly in the context of skin cancer diagnosis and treatment. Bio-inspired self-healing materials, such as dynamic disulfide-bond reorganized elastomers, mimic the skin’s natural self-repair mechanisms, achieving functional recovery through reversible chemical bond reorganization and extending device longevity [308]. Programmable degradable materials, such as photo-responsive hydrogels, allow precise control over degradation through external stimuli, aligning with different therapeutic cycles [309,310]. For instance, swellable microneedles made from polymers such as HEMA (2-hydroxyethyl methacrylate) and EGDMA (ethylene glycol dimethacrylate) show promising light responsiveness and extended drug delivery potential [311]. Future research on programmable degradable materials for wearable electronics will focus on achieving more precise control over degradation rates and drug release kinetics. Additionally, ultra-flexible conductors offer new design strategies for highly deformable regions, such as joints. Research on these conductors may focus on improving conductivity, durability under repeated deformation, and biocompatibility for long-term use in wearable devices for skin cancer diagnosis and treatment.
The advancement of detection and energy harvesting in wearable bioelectronics also depends heavily on innovations in fundamental science. For instance, several self-powered mechanisms—such as the triboelectric effect, piezoelectric effect, and the giant magnetoelastic effect—have been explored. The triboelectric effect and piezoelectric effect tend to produce higher voltage output during low-frequency mechanical movements, while MEG systems, also effective at low frequencies, are particularly optimized for periodic or repetitive motions. Since different parts of the human body exhibit varying motion frequencies, it is strategic to select appropriate energy-harvesting mechanisms tailored to specific sensing sites. Moreover, compared to TENGs, MEGs demonstrate superior performance under conditions of heavy perspiration [36]. This is because MEGs rely on mechanical deformation-induced magnetic flux variation, which remains stable even in moist or wet environments. This property opens new possibilities for waterproof and sweat-resistant device designs, particularly in applications involving biofluid extraction and integration with microneedle-based bioelectronic systems [312,313]. Advancements in energy systems must balance efficiency and biocompatibility. Enzyme-based biofuel cells (EBFCs) typically use natural enzymes to catalyze the oxidation of biofuels like glucose, lactate, and pyruvate, which are found in biological fluids such as sweat, tears, and blood, generating electricity under mild physiological conditions [314–316]. The high lactate concentration often observed in melanoma tumor microenvironments could be a specific target for enzyme-microbe synergistic fuel cells. Future research should focus on designing such systems that consider other metabolic characteristics of melanoma in addition to high lactate levels, optimizing enzyme-microbe interactions to enhance power generation and biocompatibility in skin cancer environments. Wireless energy transmission technologies, including magnetic resonance coupling and laser charging, can enable percutaneous energy replenishment [317–319]. Progress in wireless energy transmission will be critical to fully harnessing the potential of wearable electronics in skin cancer management.
The future of wearable bioelectronics is inextricably linked with advancements in artificial intelligence (AI), the IoT, and data science. These technologies are transforming wearable devices from simple data collectors into intelligent systems capable of sophisticated analysis, prediction, and personalized intervention [320,321]. Machine learning (ML) algorithms are essential for extracting meaningful insights from the complex, high-dimensional data generated by wearable sensors [322]. For skin cancer, ML can enhanced diagnostic accuracy. ML models, particularly deep learning architectures like Convolutional Neural Networks (CNNs) and Recurrent Neural Networks (RNNs), can be trained to fuse data from multiple modalities. For example, a study by Gessert et al. demonstrated that a joint deep learning model combining dermoscopic images and Electrical Impedance Spectroscopy (EIS) data significantly outperformed models using either modality alone [323]. At a clinically relevant sensitivity of 98 %, the model using only dermoscopy achieved a specificity of 34.4 %, and the model using only EIS achieved a specificity of 34.7 %. However, the combined model that fused both data sources reached a specificity of 53.7 %, a marked improvement. This data fusion approach allows the model to learn complementary features—surface morphology from the images and subsurface tissue structure and composition from the impedance data-—leading to more robust and accurate classification of skin lesions [323]. Transmitting raw physiological data to the cloud for analysis raises significant privacy and security concerns. Edge computing, which involves embedding lightweight ML models directly onto the wearable device’s microcontroller, offers a solution. This allows for real-time data processing and decision-making on the device itself, minimizing latency and ensuring that sensitive patient data never has to leave the local system [324,325]. The ultimate goal of personalized medicine is to create treatment plans tailored to an individual’s unique biology. Digital twins are virtual, patient-specific computational models that integrate a patient’s genomic data, clinical history, lifestyle factors, and real-time data from wearable sensors [326–328]. By running multiphysics simulations on this digital replica (e.g., simulating drug diffusion or tumor response to therapy), clinicians can predict how a patient will respond to different treatments, test various therapeutic strategies in silico, and optimize a treatment plan before it is ever administered to the real patient. This represents a paradigm shift from reactive to predictive and personalized cancer care.
A significant future direction for wearable bioelectronics in dermatology lies in shifting the fabrication paradigm from pre-fabricated patches to devices created directly on the body through in situ fabrication techniques. A primary limitation of conventional wearable devices is their susceptibility to motion artifacts, which arise from the mechanical mismatch and relative movement at the device-skin interface, ultimately compromising the quality and reliability of physiological data [280,329]. Drawn-on-Skin (DoS) bioelectronics represents a transformative approach to solving this long-standing challenge. This strategy utilizes functional, biocompatible inks in a liquid or sol-gel state that can be directly drawn, printed, or sprayed onto the skin [330]. The low viscosity of these precursor inks allows them to flow into the microscopic crevices of the epidermis, and upon drying or curing, they form an ultra-conformal electronic circuit that is intimately integrated with the skin’s topography. This robust, seamless interface moves synchronously with the skin, effectively eliminating the interfacial shear that causes motion artifacts and enabling the acquisition of high-fidelity, motion-artifact-free data for applications like electrophysiology (ECG/EMG) and impedance sensing [331]. For skin cancer management, this technology offers the profound advantage of on-demand customization; devices can be fabricated at the point of care to perfectly match a patient’s unique anatomy or, more specifically, to conform to the irregular geometry of a suspicious lesion for precise diagnostic monitoring or a post-surgical wound for therapeutic intervention. Furthermore, the ability to use DoS electrodes to apply localized electrical stimulation has been shown to accelerate wound healing [332], a capability with direct relevance for improving outcomes after biopsies or tumor excisions. The relative simplicity and low cost of these fabrication methods also enhance their potential for widespread adoption, particularly in resource-limited settings. Therefore, the continued development of in situ and DoS bioelectronics represents a critical step toward creating truly personalized, high-performance, and accessible wearable systems for dermatological health.
As wearable bioelectronic devices for skin cancer treatment become increasingly complex and integrated into healthcare systems, establishing clear regulatory guidelines and carefully considering ethical implications is crucial. Collecting and transmitting sensitive patient physiological data from wearable devices requires robust data privacy mechanisms to ensure patient confidentiality and trust. Data privacy protection requires the use of encryption to securely share patient physiological data, thus maintaining the security of the original patient information. Future research should focus on the development of optimized encryption schemes and efficient data transfer protocols suitable for deployment on these platforms while maintaining a high level of security and accuracy.
Regulatory agencies such as the FDA and EMA play a crucial role in setting guidelines and standards to ensure the safety and reliability of wearable electronic devices that come into prolonged contact with the skin. In September 2024, the FDA released a draft guidance on “Chemical Analysis for Biocompatibility Evaluation of Medical Devices”, providing recommendations for analytical testing to assess the safety of materials used in medical devices (including those in prolonged skin contact). While the provided draft did not specifically mention a timeline for creating durability testing guidelines for wearable electronic devices used in skin cancer treatment, the emphasis on long-term biocompatibility and the ongoing studies on the stability of materials like PDMS and silk fibroin in physiological conditions suggest that durability will be an essential factor in regulatory evaluations. Manufacturers may need to demonstrate the mechanical integrity and functional reliability of these devices over their intended lifespan, considering factors such as repeated bending, stretching, and exposure to sweat and other bodily fluids. Choosing biocompatible and durable materials (such as PDMS and silk fibroin) will be crucial to meeting these regulatory requirements.
The future of wearable electronics in skin cancer diagnosis and treatment will be marked by significant innovations in materials science, energy systems, and intelligent computing platforms. Bio-inspired self-healing materials hold promises for extending device lifespans, while programmable degradable materials offer controlled therapeutic delivery. Ultra-flexible conductors will enable seamless integration with the body. Advancements in hybrid bioenergy systems and wireless power transmission aim to provide sustainable and convenient energy. Smart closed-loop systems, utilizing lightweight edge computing and digital twin platforms, will pave the way for personalized and adaptive diagnostic and therapeutic interventions. Lastly, establishing robust regulatory and ethical frameworks will be essential to ensure the safe and responsible translation of these technologies into clinical practice, ultimately improving treatment outcomes for skin cancer patients.

8.
Conclusion
Skin cancer especially melanoma with high invasiveness and metastatic potential pose a persistent health threat. Traditional diagnostic and therapeutic methods like tissue biopsy and chemotherapy lack precision, minimal invasiveness, and dynamic regulation, creating a need for flexible bioelectronics as a transformative solution. This review highlights recent advancements in wearable electronic devices for melanoma diagnosis and treatment, emphasizing their role in reshaping precision cancer medicine through multimodal sensing, targeted therapy, and closed-loop feedback.
Flexible devices address the limitations of traditional technologies by offering non-invasive, high-resolution diagnostic capabilities. Optical sensors and electrochemical sensors enable real-time monitoring of metabolic and molecular features of melanoma, facilitating early detection. In therapy, these devices enhance efficacy and minimize systemic toxicity by delivering localized energy and smart drug release. Thermoresponsive microneedle patches enable on-demand chemotherapy drug release, while photodynamic therapy systems activate photosensitizers with wireless control for targeted treatment. Electrotherapy directly or indirectly destroys tumor cells, and immunotherapy microneedles activate immune responses, improving CD8+ T-cell infiltration. Combination therapies show improved survival and lower toxicity compared to monotherapies.
The clinical feasibility of these devices is supported by their mechanical adaptability and biocompatibility. Bio-inspired materials (e.g., PDMS, silk fibroin) allow the devices to stretch up to 300 %, conforming to the skin and reducing motion artifacts. Self-powering systems (e.g., triboelectric nanogenerators) and wireless communication (e.g., 5G) enable long-term, non-invasive operation. While challenges remain in material stability, energy efficiency, and data fusion, future developments will focus on improving device durability, dynamic optimization, and affordable healthcare solutions. Flexible bioelectronics are advancing melanoma treatment toward precision medicine, offering more efficient, safe, and accessible solutions for global patients.