Advances in flexible piezoelectrics for wearable and implantable medical devices

Abstract

Flexible piezoelectric materials have garnered increasing attention due to their potential applications in wearable and implantable medical devices. While wearable technologies provide continuous health monitoring, their reliance on batteries limits long-term usability. In contrast, implantable medical devices (IMDs) offer both monitoring and therapeutic functions, but they face challenges such as power supply limitations, biocompatibility issues and long-term stability concerns. This review focuses on the role of flexible piezoelectric nanogenerators (PENGs) in overcoming these challenges by enabling self-powered operation, high-sensitivity biosensing and therapeutic applications. We discuss how material properties, including piezoelectric performance, mechanical flexibility and biocompatibility, influence device functionality. Additionally, key challenges, including material degradation, encapsulation strategies and integration with existing medical technologies, are examined. By highlighting recent advances in PENG-based IMDs for energy harvesting, physiological monitoring and medical therapies, this review provides insights into the future development of self-sustaining and multifunctional biomedical devices.

Introduction

Recent advancements in medical care have been largely driven by technological innovations and a growing demand for more efficient, accessible and personalised healthcare solutions^1,2. The increasing prevalence of chronic conditions has highlighted the limitations of traditional healthcare models, which often rely on episodic visits and reactive treatments, failing to provide continuous, proactive care³. With the rise of mobile health technologies, healthcare is evolving toward real-time monitoring and personalised, ongoing management⁴. Wearable medical devices such as continuous glucose monitors (CGMs), electrocardiogram (ECG) monitors and blood oxygen saturation (SpO₂) sensors enable real-time tracking of health parameters, enabling individuals to stay informed about their health outside the clinical setting^5,6,7. The ability to monitor vital signs, such as blood glucose, heart rate and oxygen saturation, in real-time has been shown to be particularly beneficial for managing chronic conditions like diabetes, cardiovascular diseases and respiratory disorders⁸. These devices also facilitate early detection of health issues, enabling quicker intervention and reducing the risk of complications⁹. However, wearable devices still face notable challenges, particularly their reliance on rechargeable batteries. The need for frequent recharging disrupts continuous monitoring, limiting their effectiveness for extended use in critical health contexts¹⁰.

In contrast, implantable medical devices (IMDs) offer a more comprehensive solution by combining continuous monitoring with therapeutic interventions. For instance, pacemakers not only monitor heart activity but also deliver electrical impulses to regulate heart rhythms, effectively managing conditions such as arrhythmia¹¹. Despite their advantages, IMDs face several challenges. These challenges include the need for lightweight design and miniaturisation to ensure that devices remain minimally invasive and comfortable for patients¹². Additionally, biocompatibility is a crucial consideration, as the materials used in IMDs must be non-toxic, non-inflammatory and capable of withstanding the physiological environment of the body without causing adverse reactions^13,14. Moreover, like wearable devices, IMDs still rely on traditional batteries, which have finite lifespans and require periodic surgical replacement¹⁵. Consequently, research is focusing on developing small, safe and self-powered IMDs that can reduce dependency on external power sources, minimise surgical interventions and improve overall patient comfort and safety.

A promising solution to the limitations of battery-powered medical devices is the use of piezoelectric nanogenerators (PENGs), which convert low-intensity mechanical energy, such as the vibrations from heartbeats, muscle contractions and breathing, into electrical power to operate medical devices^16,17,18. Their operation is governed by the direct piezoelectric effect: when non-centrosymmetric materials are mechanically deformed, the relative displacement of charge centres induces dipole reorientation and charge separation, producing an electric potential¹⁹. When electrodes are attached to a piezoelectric material, mechanical deformation induces a potential difference that drives charge flow across the circuit. The polarity and magnitude of the output depend on the direction of the applied stress relative to the polarisation axis, typically described by the longitudinal and transverse modes²⁰. In biomedical contexts, these electrical outputs serve three main roles: (1) providing a sustainable power source for small electronic systems, (2) acting as transducers that convert physiological motions into measurable biosignals and (3) delivering local electrical stimuli capable of modulating tissue activity^21,22. Together, these functions illustrate how PENGs can simultaneously address energy, sensing and therapeutic needs in self-powered medical devices.

In addition to energy harvesting, PENGs function as highly sensitive biosensors, capable of detecting biomechanical signals, including blood pressure variations, cardiac rhythms and muscle activity^23,24,25. Furthermore, PENGs have demonstrated therapeutic potential in various applications, including drug delivery and nerve stimulation^26,27. By generating electrical power, PENGs can drive systems that deliver controlled medication doses or provide nerve stimulation, offering promising solutions for enhancing nerve repair and enabling its monitoring. Thus, PENGs not only provide a self-sustaining power source for medical devices but also offer multifunctional capabilities for both diagnostic monitoring and therapeutic intervention. Their integration into healthcare technologies presents a significant advancement in the development of more efficient, reliable and long-term medical devices.

This review focuses on the role of PENGs in wearable medical devices and IMDs, with primary emphasis on their application in IMDs. PENGs provide a self-sustaining power solution for IMDs by converting mechanical energy from body movements into electrical power. Beyond energy harvesting, PENGs offer sensing and therapeutic capabilities, making them multifunctional components in advanced medical systems. This review examines the various types of piezoelectric materials employed in these devices and addresses key challenges, including material degradation, biocompatibility and long-term reliability. Additionally, the complexities of integrating PENGs into sophisticated medical devices are explored. By providing a sustainable, flexible and multifunctional energy source, PENGs have the potential to revolutionise the future of IMDs, offering a more efficient and cost-effective solution for long-term, self-powered healthcare technologies.

Materials and fabrication techniques

The integration of flexible piezoelectric materials into wearable and implantable medical devices has facilitated substantial advancements in continuous health monitoring, therapeutic interventions and energy harvesting. The efficiency and functionality of these devices critically depend on the selection of piezoelectric materials and fabrication methodologies that ensure optimal biocompatibility, mechanical robustness and compatibility with biological tissues. This section systematically examines the key classes of piezoelectric materials, including inorganic, organic and composite materials, and evaluates the state-of-the-art fabrication strategies employed to tailor these materials for biomedical applications.

Piezoelectric materials for PENGs

PENGs rely on piezoelectric materials capable of converting biomechanical energy into electrical output, making material selection a pivotal factor in their performance. The fundamental characteristics that dictate the suitability of piezoelectric materials for biomedical applications include their piezoelectric coefficient, biocompatibility, stability in physiological environments and mechanical adaptability²⁸.

The advent of PENGs was fundamentally enabled by inorganic piezoelectric materials, with ZnO playing a pioneering role in the field²⁹. The first PENG device, reported by Wang et al. in 2006, was based on vertically aligned ZnO nanowire arrays, marking a significant milestone in the field by demonstrating the feasibility of converting biomechanical energy into electrical energy at the nanoscale³⁰. ZnO, a direct-bandgap (∼3.37 eV) wide-bandgap semiconductor with a non-centrosymmetric wurtzite structure, possesses intrinsic piezoelectricity³¹. Its excellent biocompatibility, chemical stability and compatibility with various nanofabrication methods make it a promising candidate for implantable sensing and neuromodulation devices³². Nevertheless, its relatively low piezoelectric output limits its practical utility, prompting intensive research into performance enhancement strategies including cationic doping, nanostructure optimisation and interfacial engineering³³. In contrast, perovskite-structured ferroelectric ceramics, such as lead zirconate titanate (PZT) and barium titanate (BTO), exhibit significantly higher piezoelectric coefficients and electromechanical coupling efficiencies³⁴. These properties stem from their inherent ferroelectricity, which allows reversible polarisation switching under mechanical or electric fields, thereby enabling superior energy conversion performance^35,36. However, the widespread application of PZT in biomedical devices is hindered by concerns regarding lead toxicity, particularly in implantable settings where prolonged exposure to physiological fluids can result in ion leaching and adverse biological interactions^37,38. In response, lead-free perovskites such as barium calcium zirconate titanate (BCZT) and potassium sodium niobate (KNN)-based ceramic materials have been developed as viable alternatives^39,40,41. These materials offer comparable piezoelectric performance while mitigating the cytotoxic effects associated with lead-containing compounds. Recent studies have focused on compositional tuning and dopant engineering to enhance their electromechanical properties while ensuring long-term stability in biological environments. Group-III nitrides, including gallium nitride (GaN) and aluminium nitride (AlN), represent another class of promising materials for implantable energy harvesters due to their excellent chemical resilience, high polarisation alignment and biocompatibility⁴². Unlike perovskite oxides, which primarily rely on external poling to induce polarisation fields, GaN-based materials exhibit intrinsic polarisation fields that enhance charge separation efficiency, leading to significantly improved piezoelectric outputs⁴³. Furthermore, their robust mechanical properties render them suitable for integration into flexible microelectromechanical systems-based biomedical platforms.

Organic piezoelectric materials have garnered significant attention due to their intrinsic flexibility, low temperature processability and biocompatibility⁴⁴. Unlike brittle ceramic-based systems, organic piezoelectric materials can readily conform to soft tissues, making them ideal for wearable and implantable medical devices. Polyvinylidene fluoride (PVDF) and its copolymers, such as poly(vinylidene fluoride-trifluoroethylene) (PVDF-TrFE), are among the most widely investigated organic piezoelectric materials due to their strong dipolar polarisation, high chemical stability and tunable crystallinity^45,46,47. The piezoelectric performance of PVDF-based materials is highly dependent on their β-phase content, which can be enhanced through stretching, poling and fabrication techniques such as electrospinning and annealing⁴⁸. Additionally, their compatibility with solution processing techniques enables scalable fabrication approaches suitable for flexible device architectures.

Building on the pursuit of sustainability and long-term biocompatibility in implantable systems, biodegradable organic piezoelectric materials have emerged as a promising alternative to conventional PVDF-based polymers. These materials possess the dual advantages of electromechanical responsiveness and the capacity for in vivo degradation, enabling the development of transient medical devices that naturally resorb after completing their therapeutic function⁴⁹. Naturally derived macromolecules, including collagen, chitin and silk fibroin, exhibit intrinsic piezoelectricity as a result of their asymmetric molecular structures^50,51,52. For instance, collagen possesses multiple non-centrosymmetric helices that give rise to measurable piezoelectric coefficients and can degrade enzymatically under physiological conditions^53,54. Aligned silk fibroin nanofibres have demonstrated both piezoelectric activity and support for cell adhesion in neural regeneration models^55,56. Chitin-based composites have also been developed into flexible, bioresorbable hydrogels for wound healing applications⁵⁷. In contrast, synthetic biodegradable polymers, such as poly(L-lactic acid) (PLLA) and polyhydroxybutyrate (PHB), offer greater tunability in terms of crystallinity, mechanical properties and degradation kinetics⁵⁸. PLLA is one of the few synthetic polymers exhibiting shear-mode piezoelectric activity, with reported d₁₄ coefficients in the range of 10-20 pC/N after thermal annealing or mechanical stretching to enhance β-phase content^59,60,61,62. PHB, although characterised by a lower piezoelectric response, offers improved thermal stability and slower hydrolytic degradation, making it more suitable for medium-term implantable applications^63,64. Low-molecular-weight crystalline materials such as amino acid-based piezoelectrics represent another class of biodegradable energy harvesters⁶⁵. Glycine, in its non-centrosymmetric γ-phase with a trigonal crystal structure, exhibits a piezoelectric coefficient (d₃₃) of approximately 10 pC/N⁶⁶. Its rapid dissolution in aqueous environments allows for the design of fully biodegradable, transient biomedical devices. Such properties make glycine-based nanogenerators attractive for short-duration biosensing applications^67,68. Additionally, dopamine-functionalised polymers have emerged as bioinspired materials that combine adhesive properties with electrical functionality⁶⁹. Polydopamine (PDA)-modified scaffolds have been explored for skin-interfacing electronics and may serve as platforms for electrically active tissue repair⁷⁰. However, their long-term piezoelectric stability and in vivo degradation profiles require further investigation.

The integration of inorganic and organic components in composite structures presents a viable strategy for optimising the trade-off between mechanical flexibility and piezoelectric efficiency. Composite materials leverage the high piezoelectric coefficients of inorganic fillers while utilising organic matrices to enhance mechanical adaptability and structural integrity⁷¹. Since the advent of PENGs, hybrid materials incorporating ceramic nanoparticles, carbon-based nanostructures (e.g. graphene and carbon nanotubes) and metallic nanowires within polymeric matrices have been extensively explored to improve device performance^72,73,74,75. Two predominant design strategies have emerged in composite piezoelectric materials: (1) low-content inorganic fillers embedded in organic matrices, which enhance flexibility while maintaining moderate piezoelectric activity, and (2) high-load inorganic composites that maximise piezoelectric output while preserving a degree of mechanical compliance^{74,75,76,77,78}. The synergy between these constituents enables the fabrication of high-performance, conformable biomedical devices suitable for long-term operation in dynamic biological environments.

Fabrication techniques

Fabrication methodologies for piezoelectric materials in biomedical applications must accommodate the requirements of flexibility, miniaturisation and large-scale reproducibility. Various processing techniques are employed depending on the material class and intended application. For inorganic materials, thin-film deposition techniques such as pulsed laser deposition (PLD) enable precise control over film thickness and crystallinity, making them suitable for high-performance microelectromechanical systems-integrated biomedical devices⁷⁹. Hydrothermal synthesis, sol-gel processing and spin-coating offer cost-effective routes for fabricating nanostructured piezoelectric films⁸⁰, while chemical vapour deposition and physical vapour deposition are widely utilised for producing high-quality GaN and ZnO thin films⁸¹. Organic and composite materials are typically processed via solution-based techniques, with electrospinning being one of the most effective methods for producing piezoelectric nanofibres⁸². Electrospun nanofibres exhibit high surface-area-to-volume ratios and can be integrated with in-situ poling to enhance their piezoelectric performance⁸³. Drop-casting and spin-coating are widely used for fabricating uniform polymer-based films, as they offer simplicity, cost-effectiveness and good control over film thickness^84,85. However, these methods are often limited in their ability to create intricate structures. In contrast, emerging additive manufacturing techniques, such as 3D printing and spray coating, have demonstrated significant potential for the scalable production of complex biomedical devices^86,87. These techniques enable precise structural design, controlled material deposition and the integration of multiple functional layers, making them well-suited for advanced healthcare applications.

Despite substantial progress in fabrication techniques, key challenges persist. A fundamental trade-off exists between piezoelectric performance and mechanical compliance, particularly in inorganic systems, which often require substrates or encapsulation to maintain structural integrity⁸⁸. Conversely, organic materials offer superior flexibility but often suffer from mediocre piezoelectric output, necessitating further material optimisation⁸⁹. Reliable encapsulation also remains a critical bottleneck, especially for implantable PENGs subjected to prolonged exposure to biofluids and dynamic mechanical conditions. Current encapsulants such as polydimethylsiloxane (PDMS) and PET provide favourable biocompatibility, flexibility and chemical stability^90,91. However, PDMS exhibits high permeability to moisture and small molecules, which can lead to degradation of electrical performance and reduced device longevity in humid or biological environments⁹². In contrast, PET offers excellent chemical and structural stability but lacks the mechanical compliance necessary to conform to soft and dynamic tissue surfaces, limiting its suitability for long-term implantable applications^93,94. Polyimide (PI) is another popular encapsulation material owing to its excellent thermal stability and mechanical strength⁹⁵. However, its long-term performance in soft tissue environments remains suboptimal due to limited conformability and potential biocompatibility under chronic implantation⁹⁶. Thus, reliable long-term encapsulation remains an unresolved issue in implantable PENG systems.

Beyond material-level challenges, reproducibility and scalability also remain critical hurdles, as many advanced fabrication techniques are constrained to laboratory-scale production, complicating their transition to industrial manufacturing. Future research efforts should focus on advancing process automation, improving material stability under physiological conditions, and refining large-scale integration strategies. By overcoming these challenges, flexible PENGs hold the potential to revolutionise self-powered biomedical devices, paving the way for the next generation of wearable and implantable health technologies.

Flexible piezoelectrics for wearable medical devices

Wearable medical devices are transforming healthcare by enabling real-time monitoring, early disease detection and personalised medicine. However, their effectiveness is often limited by the need for frequent battery charging¹⁰. Flexible PENGs provide an attractive alternative by harvesting biomechanical energy from human motion⁹⁷. Their dual functionality as energy harvesters and physiological sensors enables continuous, self-sustaining operation^98,99. This section explores recent advances in high-performance PENGs for wearable energy harvesting and sensing applications.

Harvesting PENGs for collecting biomechanical energy from the human body

Flexible PENGs have shown promise in replacing conventional batteries by utilising biomechanical energy, thereby enabling long-term autonomous operation^77,90,100. Advances in material design and device architecture have significantly enhanced their energy conversion efficiency^101,102,103. Numerous studies have demonstrated the successful collection of biomechanical energy from the human body. For example, a PENG based on a BTO-glass fibre electronic cloth (GFEC)/PVDF composite film, encapsulated by a mixed solution of mechanoluminescent particles (ZnS:Cu) and PDMS, exhibits excellent energy harvesting performance. The output voltage of this device increases with frequency, starting at 25 V at 0.5 Hz and reaching 58 V at 5 Hz under a 4 N force, due to enhanced charge generation and accumulation. The device can produce a maximum output power of 217.8 μW, with a power density of 43.56 μW/cm², which is sufficient to power various electronic devices. Voltage outputs from different body movements, such as fist beating (~50 V) (Fig. 1a), finger tapping (~25 V) (Fig. 1b) and elbow bending (~4 V) (Fig. 1c), demonstrate its efficiency in collecting energy from human activities. Additionally, its mechanoluminescent properties allow stress visualisation, adding multifunctionality¹⁰⁴.

Fig. 1: Electrical output performance of PENGs under different human motions.

Output voltage generated from BTO-GFEC/PVDF-based PENG subjected to different body movements: a Fist beating, b Finger tapping and c Elbow bending¹⁰⁴. Reproduced with permission. Copyright 2024, John Wiley and Sons. d Charging curves of capacitors powered by the PVDF/CsPbBr₃/Ti₃C₂T_x-based PENG. e Output voltage of the PVDF/CsPbBr₃/Ti₃C₂T_x-based PENG under foot stepping¹⁰⁵. Reproduced with permission. Copyright 2023, John Wiley and Sons. f Schematic illustration of the prepared BCZT@PDA/PLA-based PENG. g V_OC and h I_SC of the BCZT@PDA/PLA-based PENG. i Charging curves of the BCZT@PDA/PLA-based PENG. (Insets show a zoomed-in portion of the charging curve.)¹⁰⁶ Reproduced with permission. Copyright 2021, Elsevier.

Building on these advances, self-polarised PENGs offer additional benefits by eliminating the need for external poling fields, high temperatures and prolonged poling times, leading to energy savings and more efficient fabrication processes. A representative example is the self-polarised PVDF/CsPbBr₃/Ti₃C₂T_x composite fibre film PENG, which exhibits remarkable energy harvesting capabilities. The device is capable of charging capacitors of varying capacitances: 1, 2.2 and 10 μF within 60 s, with voltages reaching 6.3, 2.6 and 0.9 V, respectively. As shown in Fig. 1d, the charging curves of capacitors with varying capacitance values are shown. In one test, a 1 μF capacitor was charged from 0.07 V to 0.44 V over 18 working cycles, with a charging rate of 20.6 nC per cycle, highlighting the device’s substantial piezoelectric output. Additionally, the PENG can directly power 150 commercial green LEDs using a 2.2 μF capacitor and a voltage regulator, showcasing its ability to drive electronic devices without the need for external storage. Figure 1e shows the output voltage of the PVDF/CsPbBr₃/Ti₃C₂T_x composite fibre film under foot stepping, demonstrating its ability to effectively convert mechanical energy into electrical power¹⁰⁵. Expanding on the concept of self-polarised, sustainable energy harvesting, the lead-free, bio-flexible PENG developed with Ba_0.85Ca_0.15Zr_0.10Ti_0.90O₃ (BCZT) nanoparticles functionalised with PDA and embedded in a biodegradable polylactic acid (PLA) polymer matrix demonstrates exceptional performance, as illustrated in Fig. 1f. The self-polarised BCZT@PDA/PLA nanocomposite film streamlines fabrication by eliminating external poling, making the process more energy efficient. This device achieves an open-circuit voltage (V_OC) of 14.4 V (Fig. 1g) and a short-circuit current (I_SC) of 0.55 μA (Fig. 1h) under gentle finger tapping. In terms of charge storage, it effectively charges capacitors, reaching 2.8 V in 115 s, as shown in the charge-storage performance curve (Fig. 1i). Furthermore, the device delivers a maximum power output of 25 μW at a resistive load of 3.5 MΩ, exceeding the performance of previous BCZT-based PENGs by more than three times. It also achieves an area power density of 12.82 μW/cm² and a volumetric power density of 7.54 mW/cm³, outperforming many reported PENGs in energy conversion efficiency¹⁰⁶.

These examples underscore significant progress in harvesting biomechanical energy for wearable medical technologies. For energy harvesting applications, key output parameters such as V_OC, I_SC and power density are the primary indicators of device efficiency¹⁰⁷. These are influenced by intrinsic material properties, such as the d₃₃, dielectric constant (ε₃₃) and mechanical properties¹⁰⁸. In biomedical settings, additional factors such as biocompatibility, stability in physiological environments and functional lifespan are also critical. Depending on the application scenario, the relative significance of each parameter differs accordingly. Table 1 highlights representative examples of recent high-performance PENGs for energy harvesting, focusing on their material systems, fabrication methods and energy output performance. PENG development continues to advance through improvements in material performance, structural design and energy conversion efficiency. These innovations reduce dependency on batteries and move wearable health monitoring toward fully self-powered solutions.

Table 1 Comparison of representative high-performance PENG systems

PENGs for sensing vital signs

Beyond energy harvesting, PENGs have demonstrated great potential in vital sign monitoring by converting biomechanical signals into electrical outputs^109,110. Unlike conventional sensors that require external power sources, PENGs provide a self-powered alternative for continuous physiological tracking. Their high sensitivity allows for the detection of subtle biomechanical changes, making them ideal for wearable health monitoring^111,112. Recent advancements in PENG materials and device architecture have further enhanced their precision, stability and integration into medical technologies.

Cardiac monitoring is a prominent application where PENGs detect arterial pulse-induced deformations for real-time heart rate measurements¹¹³. Arterial pulse waveforms serve as critical physiological indicators, reflecting cardiovascular health, blood circulation efficiency and potential abnormalities such as hypertension or arrhythmia¹¹⁴. Chen et al. developed a highly sensitive and flexible PENG based on a single-crystalline III-nitride (III-N) thin film, demonstrating its potential for real-time, self-powered cardiac monitoring. Designed with a sandwich structure, the III-N thin film PENG can detect minute arterial deformations, producing a voltage output of ~20 mV from a single water droplet (38 ± 4 mg mass), indicating its ability to capture weak mechanical stimuli. As shown in Fig. 2a, when placed at different arterial sites, mechanical deformation bends the PENG, causing polarisation changes in the III-N thin film and generating an electrical signal. The consistent pulse waveforms observed in Fig. 2b across multiple arterial locations confirm its ability to accurately capture arterial expansion and contraction. Furthermore, the voltage response exhibits a linear correlation with deflection up to 500 μm, aligning with typical arterial pulse-induced skin deformations. Controlled deflection tests, using a motor-driven micrometre drive, validated its high sensitivity and repeatability, establishing its potential for continuous cardiovascular monitoring¹¹⁵.

Fig. 2: Wearable PENG systems for physiological monitoring across multiple body functions.

a Schematic illustration of arterial pulse measurement locations and b pulse waveforms recorded by the III-N thin-film PENGs¹¹⁵. Reproduced with permission. Copyright 2019, John Wiley and Sons. c Output voltage of a single breath cycle, showing inspiration and expiration detected by the DyW@MoS₂/PDMS-based PENG. d Comparison of output signals during nasal and oral breathing¹²¹. Reproduced with permission. Copyright 2023, Elsevier. e Schematic illustration of the PVDF/ZnO core-shell fibre-based physiological monitoring system designed for muscle behaviour analysis. f The ratio of the three calf muscles’ response amplitude between the right and left legs during different walking directions¹²⁷. Reproduced with permission. Copyright 2020, Elsevier.

Blood pressure is another critical cardiovascular parameter that PENG-based sensors can monitor non-invasively¹¹⁶. Min et al. developed a wearable piezoelectric blood pressure sensor for continuous, non-invasive monitoring of blood pressure. The sensor features a Pb(Zr_0.52Ti_0.48)O₃ piezoelectric layer (2 μm thick) on a flexible polyethylene terephthalate (PET) substrate (75 μm thick), with gold interdigitated electrodes and a PDMS passivation layer for stability. With a sensitivity of 0.062 kPa⁻¹ and a rapid response time of 23 ms, the sensor effectively captures subtle fluctuations in arterial pressure. It accurately detects subtle arterial pulse waveform changes, including the late systolic peak and mitral valve closure. A linear regression model converts the sensor’s electrical signals into blood pressure values. Clinical trials on 35 subjects showed a mean difference of −0.89 ± 6.19 mmHg for systolic blood pressure and −0.32 ± 5.28 mmHg for diastolic blood pressure compared to a commercial sphygmomanometer. Integrated into a wristwatch, this PENG enables real-time, wearable blood pressure monitoring¹¹⁷.

PENGs have also been used for respiratory monitoring, capturing chest expansion and contraction during breathing cycles^118,119. These sensors provide a non-invasive approach to tracking respiratory rate and detecting abnormalities in lung function¹²⁰. A notable example is the dysprosium tungstate (DyW)@MoS₂/PDMS-based flexible PENG, which demonstrates high sensitivity in respiratory monitoring when integrated into a smart mask, enabling real-time detection of breathing patterns. As shown in Fig. 2c, the PENG accurately captures breath cycles, distinguishing inhalation from exhalation for respiratory function assessment. It also differentiates between nasal and oral breathing (Fig. 2d), demonstrating precision and applicability in respiratory monitoring. Notably, the PENG maintains stable performance even at 90% humidity, ensuring accurate sensing under varying environmental conditions. Its high sensitivity and stability in humid environments make it particularly useful for continuous respiratory assessment in hospital and home-care settings. The PENG’s capability to detect subtle variations in breathing patterns enables early identification of respiratory distress, sleep apnoea and other pulmonary conditions¹²¹.

Beyond respiration, similar piezoelectric sensing principles can be applied to other physiological motions, where variations in deformation amplitude and frequency give rise to distinct electrical responses. Such signal characteristics allow differentiation of motion patterns associated with different activities, forming the basis for broader biomechanical monitoring. PENG-based sensors have also shown high sensitivity in detecting muscle contractions across various anatomical locations, including the fingers, wrists, elbows, knees and calves^{122,123,124,125,126,127,128}. By capturing biomechanical signals generated by muscle contractions, these sensors offer valuable insights for rehabilitation, prosthetic control and neuromuscular disease monitoring^129,130,131. Yang et al. developed a hierarchically structured PVDF/ZnO core-shell nanofibre-based piezoelectric sensor capable of detecting muscle activity with high sensitivity. As illustrated in Fig. 2e, the system consists of a three-dimensional hierarchically interlocked fibre network, where ZnO nanorods are epitaxially grown on electrospun PVDF nanofibres, enhancing mechanical flexibility, gas permeability and piezoelectric performance. The device generates an output voltage of ~0.85 V in response to muscle contractions, demonstrating its ability to convert biomechanical signals into electrical outputs with high efficiency. The sensor was integrated into a physiological monitoring system that enables real-time gait recognition, muscle activity quantification and disease rehabilitation monitoring (Fig. 2f). It accurately captures muscle activity in the calf during different walking and distinguishes variations in contraction intensity from different muscle groups, such as the tibialis anterior, gastrocnemius and soleus. These capabilities make it a promising solution for neuromuscular assessment and assistive technology development¹²⁷.

Beyond the above examples, PENG-based sensors are also being explored for advanced applications in wearable devices, including biochemical and neuromuscular signal detection. Zhao et al. developed an ultrathin (~16 μm) PENG composed of an anodic aluminium oxide insulating layer and vertically aligned ZnO nanowires. The PENG conforms to biological surfaces and detects subtle deformations, enabling real-time eyeball motion tracking when attached to the eyelid. This capability supports applications in sleep tracking, brain activity assessment and neurological disorder diagnosis¹³². Wang et al. reported a self-powered wearable electronic skin capable of performing biochemical analysis of perspiration. The device incorporates ZnO nanowires functionalised with specific enzymes, including lactate oxidase, glucose oxidase, uricase and urease, to detect lactate, glucose, uric acid and urea, respectively. The system operates through a piezoelectric-enzymatic reaction coupling mechanism, where mechanical deformation of the ZnO nanowires generates a piezoelectric potential, and enzymatic reactions modulate this signal via changes in surface carrier concentration. This enables analyte concentration to be transduced directly into an electrical output without requiring an external power source. Despite the limited lifespan caused by enzyme degradation, the system showcases a promising platform for real-time, continuous, and non-invasive metabolic monitoring during physical activity and in clinical settings¹³³.

These studies highlight the multifunctionality of PENGs in self-powered sensing. In contrast to energy harvesting, vital sign detection prioritises sensitivity, signal-to-noise ratio and response time. The relative importance of these parameters varies depending on the target physiological signal and integration scenario. Eliminating batteries enables uninterrupted monitoring and supports early diagnostics. With continued innovations in material and device engineering, PENGs offer scalable, long-term solutions for high-performance biomedical sensing¹³⁴.

Flexible PENGs for in vivo IMDs

IMDs are essential for long-term health management, enabling continuous monitoring, therapeutic intervention and life-sustaining functions. Unlike wearable systems, IMDs must satisfy stringent demands for biocompatibility, mechanical durability and power sustainability. Integrating PENGs into these devices offers a self-sustained power source, reducing battery dependence and minimising surgical replacements. Moreover, PENGs can convert biomechanical signals into electrical outputs for real-time monitoring and support therapeutic functions such as electrical stimulation (ES) for tissue repair. By combining energy harvesting, sensing and treatment, PENGs are driving the development of autonomous, multifunctional IMDs.

Energy harvesting PENG integrated with medical devices

Unlike externally worn systems, IMDs require reliable, long-term internal power. PENGs offer in vivo energy harvesting capabilities, mitigating battery-related limitations¹³⁵. A representative example is a high-performance PENG based on single-crystalline (1-x)Pb(Mg_1/3Nb_2/3)O₃-xPb(Zr, Ti)O₃ (PMN-PZT) thin film developed by Kim et al. As shown in Fig. 3a, this system is capable of wirelessly transmitting communication data using energy harvested from porcine heartbeats. Notably, the feasibility of this system was visually demonstrated by repeatedly switching a light bulb on and off at a long distance of approximately 5 m, without any external power source. When implanted in a porcine heart, the flexible PENG generated a V_OC of 17.8 V (Fig. 3b, top) and an I_SC of 1.75 μA (Fig. 3b, middle), significantly outperforming previous in vivo piezoelectric energy harvesters. The electrical output signals of the flexible PENG were well synchronised with the ECG signals of the porcine heart (Fig. 3b, bottom). Due to its precise alignment with ECG signals, the energy harvester can be applied as a cardiac monitoring sensor. This dual functionality enhances its potential as a self-powered implantable biomedical system, enabling both real-time physiological monitoring and sustainable power generation for medical implants¹³⁶. Another example involves a Pb(Mg_1/3Nb_2/3)O₃-PbTiO₃ (PMN-PT) based PENG designed to directly power pacemakers. As shown in Fig. 3c, the device consists of three primary layers: an encapsulation layer, a piezoelectric composite layer and an elastic skeleton layer. Given the inherent toxicity of PMN-PT, a protective encapsulation layer was employed to ensure biocompatibility, which was further validated through cytotoxicity assessments. The elastic skeleton, which serves as the core structure, is made of a PET sheet shaped into a capsular ‘8’ configuration. This design enables compression and rapid rebound, enhancing mechanical energy conversion efficiency. To evaluate its in vivo performance, the PENG was implanted at different locations within a porcine heart, including the apex, anterior wall, posterior wall and lateral wall. Among these positions, the apex demonstrated the highest energy output, with a maximum V_OC of ~20 V and a maximum I_SC of ~15 μA. The device implanted at the apex was connected to a pacemaker via a rectifier, enabling direct energy transfer to sustain pacemaker operation (Fig. 3d). The pacing pulses generated by the PENG-powered pacemaker were consistent with those produced by a battery-powered pacemaker (Fig. 3e), confirming the stability and reliability of the energy supply¹³⁷.

Fig. 3: Implantable PENGs for cardiac energy harvesting and pacemaker powering.

a Schematic of an in vivo system where a flexible PENG harvests cardiac energy for wireless monitoring. b V_OC, I_SC and ECG signals of the implantable PMN-PZT-based PENG generated from the porcine heartbeat¹³⁶. Reproduced with permission. Copyright 2017, John Wiley and Sons. c Structure of the implantable PENG, showing encapsulation, piezoelectric and elastic layers. d The implanted device is placed on the apex and connected to the pacemaker via a rectifier. e Pacing pulses from battery-powered vs PENG-powered pacemaker¹³⁷. Reproduced with permission. Copyright 2019, American Chemical Society. f–h Electrical performance of the ZnO-rGO/PVDF-based PENG: f Output energy measured across varying load resistances. g Charging curves of a 100 μF capacitor. Insets show a commercial pacemaker before and after lithium battery removal. h Pacing pulses are generated by the pacemaker, powered by PENG⁷⁵. Reproduced with permission. Copyright 2021, Elsevier.

Although lead-based piezoelectric materials exhibit excellent energy harvesting capabilities, their toxicity remains a major concern, particularly for IMDs. Therefore, developing lead-free, flexible and biocompatible alternatives has become a crucial focus in the field of implantable PENGs. To address this issue, Azimi et al. developed a flexible and biocompatible PENG for a self-powered cardiac pacemaker. The PENG consists of PVDF nanofibres with a 0.1 wt% ZnO: reduced graphene oxide (rGO) (90:10) hybrid filler, which improves piezoelectric performance and charge transfer efficiency. The optimised design led to a nearly 10-fold increase in output voltage compared to pristine PVDF nanofibres and achieved a power density of 138 μW/cm³ under 1 Hz mechanical excitation. The biosafety of the encapsulated PENG was confirmed through in vitro cytotoxicity assessments. Electrical output across load resistances further validated its efficient energy conversion. (Fig. 3f). When sutured onto the left ventricle of a canine heart, it harvested 0.487 μJ per heartbeat, generating enough energy to power a commercial cardiac pacemaker. As shown in Fig. 3g, the charging characteristics of a 100 μF capacitor powered by the ZnO-rGO/PVDF-based PENG were analysed, demonstrating its capability to accumulate and store energy for biomedical applications. The PENG-powered pacemaker produced pacing pulses comparable to those of a battery-powered pacemaker, confirming its stable and reliable energy supply (Fig. 3h).

These studies highlight the rapid advancement of energy-harvesting PENGs for IMDs. By enabling sustainable, battery-free operation and integration with sensing or therapeutic functions, PENGs offer a promising route toward long-lived, autonomous implantable systems.

PENGs for implantable diagnostic and therapeutic devices

Beyond serving as self-powered transducers, implantable PENGs increasingly function as continuous sensing platforms for long-term physiological monitoring. In contrast to conventional implantable sensors that rely on discrete measurements or external power sources, PENG-based systems convert biomechanical activities such as arterial pulsation, blood pressure fluctuation and tissue deformation into time-resolved electrical waveforms. These signals encode both instantaneous physiological states and longer-term trends, enabling quantitative waveform analysis and data-driven interpretation to support diagnostic monitoring and therapeutic assessment. This section reviews representative implantable PENG platforms for diagnostic and therapeutic applications, with particular emphasis on how signal characteristics, operational stability and emerging data interpretation strategies enhance their clinical relevance and translational potential.

In cardiovascular diagnostics, implantable PENG sensors exhibit high sensitivity and energy autonomy, making them ideal for long-term tracking of critical parameters¹³⁸. For example, in a clinical setting, integrating a miniaturised piezo force sensor into a medical catheter for real-time intrabody pressure monitoring can significantly enhance procedural safety and clinical decision-making during procedures such as bronchoscopy. The proposed medical catheter, equipped with a piezoelectric force sensor and an electronic interface for data recording, enables real-time monitoring of airway pressure during the procedure (Fig. 4a). With a responsivity of 0.63 μV/Pa across a 40 kPa range, the system provides quantitative feedback capable of reducing the risk of airway tissue injury. Figure 4b further highlights the potential for deploying similar sensors near critical arteries, such as the carotid, in implantable formats. The device incorporates wireless power harvesting and demonstrates an operational lifetime of approximately 400,000 loading cycles under physiological conditions. It can transmit data to a mobile phone interface, enabling long-term haemodynamic surveillance without repeated surgical intervention. This self-sustaining PENG platform enables autonomous monitoring of major arteries such as the carotid and radial arteries, thereby supporting early identification of vascular abnormalities, including atheroma development or arterial rupture¹³⁹.

Fig. 4: Implantable PENG systems for physiological monitoring across multiple organ systems.

a Schematic of a bronchoscopy catheter integrated with a piezoelectric force sensor and data interface. b Diagram of an implantable PENG system near the carotid artery enabling wireless pressure monitoring and data transmission¹³⁹. Reproduced with permission. Copyright 2020, American Chemical Society. c Schematic of a self-powered PENG-based system for real-time hypertension detection with a battery-free LCD alarm. d Device components and in vitro setup: the sensor wraps around a latex tube and activates the LCD as pressure exceeds 120 mmHg. e In vivo setup showing the device implanted on the aorta and LCD fixed to the thoracic wall. f The LCD activates when systolic blood pressure exceeds 140 mmHg⁴⁵. Reproduced with permission. Copyright 2016, Elsevier. g, h Photographs of a PZT-based gastrointestinal PENG sensor attached to the stomach wall during inflation. i Voltage output recorded during (i) a water infusion and suction cycle and (j) a full air inflation and deflation cycle¹⁴⁴. Reproduced with permission. Copyright 2017, Springer Nature.

Cheng et al. demonstrated the significant potential of implantable PENG-based sensors for continuous blood pressure monitoring. As shown in Fig. 4c, the system utilises PVDF-based PENG to harvest biomechanical energy from natural blood flow and arterial pulsations, converting it into electrical signals for real-time cardiovascular monitoring. The PVDF-based PENG in this system exhibits high sensitivity and responsiveness to pressure variations, allowing for precise detection of subtle haemodynamic fluctuations. During in vitro evaluations (Fig. 4d), the device was wrapped around a latex tube to simulate blood vessels, demonstrating a strong linear correlation between output voltage and applied pressure. The battery-free liquid crystal display remained inactive below 120 mmHg but sequentially displayed numerals as pressure increased, offering an intuitive real-time visual output. In vivo studies further validated the device’s reliability and efficiency. The implantable PENG was securely wrapped around the aorta of a porcine model, with a battery-free liquid crystal display fixed onto the thoracic wall (Fig. 4e). Under physiological conditions, the device consistently generated stable voltage signals corresponding to blood pressure variations. Notably, when systolic blood pressure exceeded 140 mmHg, the display activated, providing a clear visual alert of hypertensive conditions (Fig. 4f). This feature enables timely visual identification of hypertensive events, enabling timely identification and potential early clinical intervention⁴⁵.

Beyond device-level pressure sensing, the clinical value of implantable PENG systems lies in the interpretation of continuously recorded cardiovascular waveforms. Time-resolved pressure signals enable the extraction of quantitative features such as peak-to-peak amplitude, temporal variability, pulse morphology and cycle-to-cycle consistency, which reflect arterial compliance, vascular stiffness and overall haemodynamic stability^140,141. On this basis, data-driven models can be applied to estimate vascular parameters and to distinguish physiological from pathological haemodynamic patterns, particularly in long-term monitoring scenarios¹⁴². Collectively, these data-driven interpretation strategies transform implantable PENG sensors from passive signal collectors into quantitative and intelligent tools for cardiovascular assessment, with reliable long-term deployment contingent on signal stability and calibration.

More broadly, data-driven signal-model-decision pipelines for PENG time-series data have been demonstrated across different sensing contexts, providing transferable frameworks beyond a single organ system. Representative implementations of such data-driven interpretation pipelines have already been demonstrated in PENG-based sensing systems. For instance, Guo et al. developed a self-powered flexible piezoelectric sensor patch for wrist joint motion identification and rehabilitation monitoring. Benefiting from the high sensitivity of the PVDF-based PENG sensor (0.2768 V/kPa), time-series electrical signals associated with wrist movements were analysed using a long short-term memory neural network, achieving a classification accuracy of 92.6% across six common wrist joint motions. This work highlights how AI (artificial intelligence)-driven data interpretation can elevate PENG-based self-powered sensors from passive signal collectors to intelligent platforms capable of motion recognition and personalised rehabilitation assessment. Importantly, this signal-model-decision pipeline is generalisable and can be extended to implantable PENG systems for continuous physiological waveform interpretation. Moreover, the self-powered operation reduces system-level energy consumption, supporting long-term, continuous monitoring without reliance on external power sources¹⁴³. With this perspective on transferable data interpretation strategies, the following sections summarise representative PENG-based platforms for monitoring dynamic physiological processes across other organ systems.

In addition to cardiovascular applications, PENG-based sensors also offer significant advantages in tracking dynamic physiological processes within other organ systems. In particular, their ability to detect biomechanical movements makes them well-suited for monitoring gastrointestinal motility, a critical factor in diagnosing and treating digestive disorders. As demonstrated in Fig. 4g, h, a PZT-based PENG gastrointestinal sensor was delivered to the stomach via a gelatin-based dissolvable capsule, which disintegrates upon contact with gastric fluid. Once released, the sensor autonomously unfolds and adheres to the stomach lining, enabling real-time monitoring of gastric motility. The device integrates a PZT thin film on a flexible substrate and is hermetically encapsulated to prevent exposure to biological fluids. The sensor’s mechanical flexibility ensures stable operation within the dynamic gastrointestinal environment while minimising tissue irritation. In Fig. 4i, the representative voltage output over time for a cycle of water infusion and suction highlights the sensor’s ability to track pressure changes corresponding to controlled liquid movement inside the stomach. The distinct voltage fluctuations indicate real-time responsiveness to variations in intragastric pressure, demonstrating the sensor’s potential for detecting abnormal motility patterns. Voltage outputs recorded during complete inflation and deflation cycles further validate the sensor’s capability for continuous monitoring of stomach expansion and contraction (Fig. 4j).The clear signal correlation with different motility states suggests that this technology can provide quantitative assessments of peristaltic activity, facilitating early diagnosis and management of gastrointestinal disorders. Beyond motility monitoring, the device exhibits high mechanical durability, maintaining electrical stability over 10,000 bending cycles, and has been validated for biocompatibility through cell culture studies¹⁴⁴. These implantable PENG systems demonstrate high sensitivity, durability, and integration capability across multiple organ systems. By coupling energy harvesting and sensing in a battery-free platform, they offer reliable, long-term solutions for diagnostic and therapeutic monitoring.

While PENG-based sensors excel in physiological monitoring, they also serve as active therapeutic tools by directly converting biomechanical energy into ES. A notable example of this is ultrasound-driven wireless ES for peripheral nerve regeneration, as illustrated in Fig. 5a. Wu et al. developed a biodegradable PENG composed of KNN nanowires, PLLA and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), designed to provide adjustable, in vivo ES to implanted biodegradable nerve conduits upon ultrasound excitation. To facilitate nerve regeneration, biodegradable nerve conduits serve as scaffolds to bridge the injured peripheral nerve gap and provide structural and biochemical support for axonal growth. In this study, hydroxyethyl cellulose (HEC)/soy protein isolate (SPI)/black phosphorus (BP) composite nerve conduits were employed as an electrically conductive and biodegradable scaffold for guiding nerve repair. The incorporation of BP nanosheets into the HEC/SPI matrix enhances the electrical conductivity of the conduit, enabling efficient transmission of electrical signals from the PENG to regenerate nerves. Additionally, the mechanical properties of the HEC/SPI/BP composite nerve conduit were optimised to provide adequate support throughout the nerve healing process while gradually degrading in physiological conditions. The conduit’s impedance (~4 kΩ) closely matches that of peripheral nerves, ensuring effective ES transmission for enhanced nerve regeneration and functional recovery. The biodegradability and long-term stability of the PENG system were confirmed through in vivo degradation studies. As shown in Fig. 5b (top), micro-CT imaging demonstrated the gradual degradation of the PHBV/PLLA/KNN-based PENG over a 32-week period in vivo. Figure 5b (bottom) presents biodegradation assessments conducted in phosphate-buffered saline (PBS) solution at 37 °C, simulating physiological conditions. Both in vivo and in vitro assessments at 0 and 32 weeks confirmed the controlled degradation profile, ensuring that the PENG remains functional over the required therapeutic period while avoiding the need for surgical removal. This system enables on-demand, non-invasive neuromodulation, facilitating axonal regrowth and neuromuscular reconnection, both of which are essential for the restoration of peripheral nerve function. The therapeutic efficacy of the ultrasound-driven ES system was further evaluated in a rat sciatic nerve injury model, where quantitative assessments of muscle recovery were conducted. The results demonstrated a significant improvement in muscle weight recovery ratio (Fig. 5c) and muscle fibre cross-sectional area (Fig. 5d) following ultrasound-driven ES, with outcomes closely matching those of the autograft group, the clinical gold standard for peripheral nerve repair. This platform also allows non-invasive electrophysiological monitoring, avoiding conventional wired assessments²⁷.

Fig. 5: Implantable PENG platforms for ultrasound-driven electrical stimulation and nerve regeneration.

a Schematic of ultrasound-driven wireless ES for peripheral nerve regeneration. b Micro-CT images showing the in vivo degradation of the PHBV/PLLA/KNN-based PENG and its biodegradation in PBS solution. Statistical analysis of c gastrocnemius muscle weight recovery and d muscle fibre cross-sectional area at 4 and 12 weeks across different nerve conduit groups²⁷. Reproduced with permission. Copyright 2022, Elsevier. e Schematic of wireless stimulation of peripheral nerves using a PENG with ultrasound-controlled output. f Biocompatibility assessment on various materials. g Electrical output of the implanted PVDF/BCZT@PDA-based PENG was recorded immediately after surgery and two months post-implantation⁷⁴. Reproduced with permission. Copyright 2021, Elsevier.

Another promising approach in wireless neurostimulation involves the use of soft, implantable PENG that can be remotely modulated by external ultrasound excitation. As illustrated in Fig. 5e, this strategy enables the construction of programmable, battery-free neurostimulators, offering a novel solution for precise and adaptive neuromodulation. The ES system is based on a PENG composed of PVDF and BCZT nanowires, with a PDA coating to enhance interfacial bonding. This high-performance PVDF/BCZT@PDA-based PENG can be wirelessly powered by ultrasound, enabling direct stimulation of peripheral nerves, such as the sciatic nerve, without the need for batteries or accessory rectifiers. A key advantage of this system lies in its programmability, as the ES parameters, including current density, pulse width and frequency, can be precisely regulated by adjusting the ultrasound parameters. This capability offers a higher degree of control compared to conventional battery-free stimulators driven by body movements, which lack the ability to finely modulate stimulation intensity and timing. The biocompatibility of the PVDF/ BCZT @PDA composite was evaluated through cell viability assays, as shown in Fig. 5f, where L929 mouse fibroblasts cultured on the nanogenerator components exhibited comparable growth and viability to those on standard substrates, confirming the cytocompatibility of the device materials. Additionally, the long-term stability of this wireless neurostimulation system was assessed through in vivo implantation in rats. As demonstrated in Fig. 5g, the electrical output of the PENG remained stable over a 2-month period post-implantation, with no significant performance degradation. Furthermore, histological analysis revealed no apparent inflammatory response around the implantation site, highlighting the excellent biocompatibility and long-term reliability of the device within a biological environment⁷⁴.

PENGs also support regenerative medicine in orthopaedics. The ability to generate localised pulsed direct current stimulation makes them effective in enhancing osteogenic differentiation, providing a self-powered solution for bone regeneration. This shape memory-based PENG (sm-PENG) converts biomechanical energy into pulsed direct current stimulation, effectively promoting osteogenesis in MC3T3-E1 preosteoblast cells without the need for external power sources. Its shape memory structure enables the generation of up to 20 μA ISC, effectively enhancing MC3T3-E1 preosteoblast proliferation, intracellular calcium levels and alkaline phosphatase activity, all of which are essential for bone formation and matrix mineralisation. Notably, these biological effects were comparable to those induced by commercial signal generators, validating their therapeutic efficacy. To facilitate practical use, the sm-PENG was integrated with a fixation splint to ensure stable stimulation during movement. This flexible, self-powered system supports targeted bone repair without wiring or battery replacements. In vitro studies confirmed its ability to enhance calcium deposition and extracellular matrix mineralisation, underscoring its potential for treating fractures, osteoporosis and post-surgical bone healing. By providing a non-invasive, battery-free ES strategy, the sm-PENG offers a promising advance in bone tissue engineering¹⁴⁵.

Beyond energy harvesting and sensing, PENGs have demonstrated potential in promoting tissue regeneration through localised ES. One example is a bioinspired hybrid patch comprising a mussel-adhesive hydrogel and aligned PVDF nanofibres, which conformally contacts wound surfaces and generates voltage from body motion. The induced ES promotes fibroblast proliferation, collagen deposition, angiogenesis and re-epithelialisation, reducing wound closure time by ~33% in full-thickness skin defect models. It also modulates regenerative markers, including CD31, VEGF-A and TGF-β1, enhancing repair and reducing inflammation¹⁴⁶. PENGs have also been integrated into microneedle-based transdermal drug delivery systems for treating psoriasis. The patch incorporates conductive microneedles and drug-loaded ones containing dexamethasone. During joint motion, the PENG generates electrical signals that trigger drug release. This on-demand system improves drug penetration, suppresses inflammation more effectively than topical therapy, and reduces systemic side effects. In animal models, significant symptom relief was achieved within five days¹⁴⁷.

Wireless energy transfer via PENG typically involves the use of external mechanical stimuli, such as focused ultrasound, to activate implanted PENG, enabling energy harvesting, therapeutic stimulation, or data communication without wired connections. Another notable example is the flexible lead-free piezoelectric array developed by Yoon et al., which achieves high-efficiency wireless ultrasonic energy transfer and low-power communication. This system, based on a KNN composite PENG, successfully demonstrates simultaneous wireless powering and data transmission under focused ultrasound, enabling real-time communication with an implantable device. The wireless energy harvesting efficiency reached over 37% at 1 MHz with miniaturised receivers, illustrating a promising platform for fully untethered bioelectronic systems¹⁴⁸. These representative studies highlight a distinct class of wireless energy transfer mechanisms via PENGs, in which external ultrasound acts as both a mechanical activator and a communication channel. This emerging capability not only eliminates the need for bulky batteries or transcutaneous wiring but also enables precise spatiotemporal control over stimulation and signal transmission, paving the way for fully autonomous therapeutic systems

While PENGs offer promising capabilities, some neuromodulation applications require higher output and precise stimulation control. To meet these demands, Chen et al. developed an ultrasound-driven, battery-free PTENG for deep brain stimulation (DBS) in Parkinson’s disease. As shown in Fig. 6a, Chen et al. designed a flexible, high-performance hybrid piezoelectric-triboelectric nanogenerators (PTENGs) of PVDF nanofibres coated with trimethylchloromethylammonium trichloromanganese (TMCM-MnCl₃) molecular piezoelectric nanocrystals, which effectively integrates TENG and PENG mechanisms to optimise energy harvesting and neuromodulation efficiency. As illustrated in Fig. 6b, the subcutaneously implanted PTENG was used to wirelessly deliver ES to the subthalamic nucleus in Parkinson’s disease rat models via daily 30-minute ultrasound treatments over four weeks. The open field test tracked locomotor activity before treatment and at post-treatment days 1 and 28. The stimulation parameters were carefully optimised to include an ultrasound frequency of 100 kHz, pulse width of 60 μs, pulse interval of 10 ms and an acoustic power density of 25 mW/cm². The locomotor activity traces showed a significant improvement in spontaneous movement patterns, demonstrating the functional recovery of motor deficits following PTENG-mediated DBS therapy (Fig. 6c). Further neurophysiological analysis was performed to assess the electrophysiological response to ultrasound-driven DBS. As shown in Fig. 6d, power spectral density analysis of the striatum before and after 30 min of DBS treatment revealed a reduction in aberrant beta oscillations, a hallmark of Parkinsonian motor dysfunction. Additionally, quantitative evaluations of motor function, specifically analysing total distance travelled (Fig. 6e), maximum speed (Fig. 6f) and activity time (Fig. 6g) in the open field test, were conducted across different experimental groups (Control, PTENG only, Ultrasound only and PTENG + Ultrasound). The PTENG + Ultrasound group exhibited significant improvements (P < 0.05) compared to all other groups, demonstrating the therapeutic efficacy of this wireless neurostimulation approach. This system eliminates implantable batteries by wirelessly harvesting energy from ultrasound and allows precise modulation of stimulation parameters through ultrasound control. Biocompatibility and device stability were validated over eight weeks, with no signs of inflammation or functional degradation. These findings demonstrate that PTENGs can overcome key limitations of conventional DBS and support the development of self-powered, programmable neurostimulation systems¹⁴⁹.

Fig. 6: Ultrasound-driven implantable PTENG for wireless deep brain stimulation and neuromodulation.

a Schematic illustrating wireless DBS using PVDF/TMCM-MnCl₃-based PENG for ultrasound-driven ES. b Illustration of ultrasound-driven DBS using a subcutaneously implanted PTENG, with Parkinson’s disease model rats receiving 30-min daily ultrasound treatments for 4 weeks. c Open field test tracking locomotor activity pre-treatment and on days 1 and 28 post-treatment. d Power spectral density of the striatum before and after 30 min of DBS, showing reduced beta oscillations. Quantitative assessments of motor function in the open field test: e total distance travelled, f maximum speed and g activity time across different experimental groups (n = 6, P < 0.05)¹⁴⁹. Reproduced with permission. Copyright 2023, American Chemical Society.

Recent advances in biosignal analytics have established robust frameworks for the interpretation of long-duration physiological time-series data using machine-learning and data-driven algorithms¹⁵⁰. These approaches focus on extracting quantitative features from complex electrical signals, such as waveform morphology, temporal dynamics and signal variability, enabling systematic assessment of physiological states under real-world operating conditions. In cardiovascular research, similar analytical strategies have been extensively applied to continuous waveform signals for tasks including blood pressure estimation, trend analysis and anomaly detection, demonstrating the clinical value of quantitative, time-resolved signal interpretation in long-term monitoring scenarios¹⁵¹. In parallel, AI-assisted data analysis has been increasingly discussed in the context of neurotechnology, particularly for supporting functional evaluation and adaptive neuromodulation, while also highlighting the importance of interpretability and clinically meaningful output metrics for in vivo applications¹⁵². In implantable PENG-based systems, raw electrical outputs are typically processed through dedicated analysis strategies to derive quantitative metrics rather than being used directly as endpoints. Signal amplitude and current outputs are commonly calibrated to define effective stimulation doses or operational thresholds, while time-domain waveform features, such as pulse width and rise-fall characteristics, are extracted to characterise discrete stimulation or physiological states. Temporal signal stability is evaluated through statistical analysis of drift and variability over implantation time, and frequency-domain features are analysed to identify deviations from baseline neuromodulation patterns. For longer-term deployments, longitudinal modelling of signal evolution further supports the assessment of therapy-induced changes over days to weeks. Together, these analysis-to-metric mappings provide a practical basis for translating PENG-generated electrical signals into quantitative indicators for performance evaluation and therapeutic monitoring.

Overall, implantable PENG-based devices demonstrate a distinctive capability to integrate mechanical energy harvesting, electrical signal generation and therapeutic actuation within a single implantable architecture. Across diagnostic and therapeutic examples, these systems enable physiological signals and stimulation responses to be captured and modulated in situ, supporting continuous monitoring alongside active intervention without reliance on implanted batteries. This multifunctional integration extends the role of PENGs beyond passive sensing or standalone energy harvesting, positioning them as versatile platforms for long-term implantable diagnostics, neuromodulation and regenerative therapies under in vivo conditions.

Integration of PENGs with emerging technologies for biomedical applications

Building upon the implantable sensing and therapeutic systems discussed in Section ‘PENGs for implantable diagnostic and therapeutic devices’, emerging integration with wireless communication and AI-driven analytics is expected to reshape PENG-based biomedical platforms. The rapid advancements in flexible electronics, wireless communication and AI have created new opportunities for self-powered biomedical devices. While PENGs have demonstrated potential as energy harvesters and biosensors, their practical implementation depends on seamless integration with emerging technologies to enhance efficiency, functionality and long-term reliability. This section explores three key technological frontiers driving the next phase of PENG development.

The transition from rigid, bulky medical implants to flexible, bio-integrated devices requires advances in miniaturisation and material engineering. Recent developments in soft electronics and stretchable nanomaterials have enabled the fabrication of ultrathin, conformal PENGs capable of interfacing with dynamic biological tissues without compromising mechanical integrity¹⁵³. In particular, hybrid organic-inorganic composites have shown promise in enhancing piezoelectric coefficients while maintaining flexibility¹²⁶. Beyond material selection, advanced fabrication techniques such as 3D printing and additive manufacturing allow for scalable, high-precision device architectures^154,155. These innovations not only facilitate patient-specific medical implants but also address challenges in reproducibility and large-scale production, which are crucial for commercialisation.

For implantable PENGs, reliable wireless transmission of energy and data is crucial to avoid frequent surgical interventions for battery replacements¹⁴⁸. While biomechanical energy harvesting can provide partial power, hybrid approaches such as ultrasound-based energy transfer are necessary to support devices with higher energy demands^156,157. Additionally, integrating PENGs with the Internet of Things (IoT) enables real-time health monitoring and remote diagnostics. For instance, wireless biosensor data, such as cardiac rhythms or neural activity, can be transmitted to cloud-based platforms for AI-driven analysis, aiding in early disease detection and personalised treatment. However, these advancements also raise cybersecurity concerns, highlighting the need for secure encryption methods and interference-resistant data transmission protocols to protect patient privacy and system integrity¹⁵⁸.

AI and machine learning are transforming biomedical diagnostics, personalised medicine and autonomous therapeutic systems. When integrated with PENG-based sensors, AI enhances signal processing accuracy, anomaly detection and adaptive energy management. For PENG-based systems, the primary challenge for AI integration lies not in algorithm availability but in the acquisition of stable, longitudinal datasets under variable biomechanical and physiological conditions, which is essential for reliable model training, calibration, and on-device deployment. In this context, data-driven algorithms, including deep learning models, can be applied to PENG-generated biosignals to support automatic recognition of physiological patterns and state changes across diverse biomedical contexts, such as cardiovascular and neuromuscular monitoring^159,160. Nevertheless, translating AI-assisted PENG systems into practical healthcare applications requires not only large, high-quality datasets but also robust frameworks for real-time processing and secure integration across clinical infrastructures. Progress in these directions will be essential to realise on-device intelligence and closed-loop control, positioning PENG-enabled platforms as viable components of next-generation, responsive healthcare systems.

As shown in Fig. 7, PENG-based wearable and implantable devices enable continuous biomechanical energy harvesting, physiological signal acquisition and therapeutic stimulation for smart healthcare applications. These devices wirelessly transmit real-time health data through 5G, Bluetooth, or Wi-Fi to personal electronics, which forward the information to cloud-based IoT platforms. There, the data can be analysed using AI algorithms to support remote diagnostics, individualised treatment planning and population-level health surveillance by hospitals, research institutions and public health agencies. In advanced closed-loop systems, AI-generated feedback can be transmitted back to the PENG device to autonomously modulate therapeutic outputs without requiring clinician intervention. This paradigm exemplifies the potential of PENG-enabled platforms to support self-powered, interconnected healthcare systems through the integration of energy harvesting, wireless communication and adaptive analytics.

Fig. 7

IoT-integrated healthcare system utilising PENGs for energy harvesting, sensing and wireless data transmission to cloud platforms for real-time monitoring and medical diagnostics.

Conclusion

Flexible PENGs have emerged as vital components in next-generation wearable and implantable medical devices. Progress in material engineering, fabrication and system integration has enabled flexible, stretchable and biodegradable systems for self-powered energy harvesting, physiological sensing and therapeutic stimulation. However, critical challenges remain that must be addressed to support clinical adoption.

Current challenges

The practical application of flexible PENGs is constrained by several key challenges that require coordinated innovations across materials, devices and systems:

• (1) Energy conversion efficiency: Flexible PENGs often trade off piezoelectric performance for mechanical compliance, leading to low β-phase content and weak dipole alignment in soft matrices. While composite strategies offer improvement, output enhancement remains essential for powering real-world biomedical systems¹⁶¹.

• (2) Material stability: Physiological environments impose continuous mechanical, chemical and biological stresses. Ensuring long-term structural and functional stability under these conditions is critical for reliable device performance.

• (3) Biocompatibility: Developing piezoelectric materials that meet biocompatibility standards without compromising electromechanical function remains unresolved. Materials must minimise cytotoxicity and inflammatory responses while sustaining long-term performance.

• (4) Encapsulation strategies: Chronic implantation demands encapsulants that withstand mechanical deformation, biochemical attack and biofluid infiltration. Most current materials lack validation for prolonged use in soft biological environments, limiting device longevity and clinical reliability.

• (5) System integration: Realising compact, flexible systems that seamlessly integrate energy harvesting, sensing and wireless modules remains technically complex. Mechanical robustness, energy efficiency and system-level design optimisation are required^162,163.

• (6) Clinical translation: Scaling up fabrication, establishing effective sterilisation protocols, ensuring certified biocompatibility and validating long-term performance remain significant challenges. In vivo deployment further requires stable device fixation and minimisation of immune and inflammatory responses to avoid tissue irritation¹⁶⁴. Additionally, regulatory frameworks for emerging self-powered bioelectronics are still under development, and their approval will depend on compliance with established medical device safety and testing standards¹⁶⁵.

Perspectives

Overcoming the fundamental limitations of flexible PENGs requires a systematic and interdisciplinary approach. At the material level, the key challenge remains to simultaneously achieve high piezoelectric output, mechanical flexibility and biocompatibility. Biodegradable piezoelectric materials are essential for transient implants. To maximise energy output while preserving mechanical adaptability, hybrid energy harvesting approaches that couple piezoelectric, triboelectric and thermoelectric mechanisms offer a promising direction^55,166.

Encapsulation strategies must evolve to meet industrial standards for sterilisation, manufacturability and regulatory compliance while ensuring barrier stability in moist, dynamic environments. System-level advancement depends on seamless integration with AI, IoT and low-power wireless modules. Innovations in ultra-low-power electronics and encrypted communication will be key^167,168,169. Finally, the successful translation of PENG technologies into clinical practice must address industrial scalability, economic feasibility and early alignment with clinical workflows and regulatory¹⁷⁰ strategies.

Future outlook

Flexible PENGs represent a major step toward autonomous, sustainable biomedical systems. Looking ahead, their successful deployment will depend on continued advances in materials design, system integration, energy management and long-term biocompatibility. Human physiological environments demand devices that are not only mechanically adaptable but also chemically and functionally stable over long durations.

Future research should prioritise multifunctional, biodegradable and intelligent piezoelectric platforms that integrate seamlessly with both biological systems and digital healthcare infrastructure. Advances in hybrid energy harvesting, wireless connectivity and AI-driven closed-loop feedback will be essential for achieving real-time health monitoring and personalised therapy. Collaboration across materials science, electronics, bioengineering and clinical disciplines will be vital to overcome current barriers and accelerate innovation. With continued interdisciplinary effort, flexible PENGs are poised to revolutionise smart, self-powered medical technologies in the decade ahead.