Piezoelectric interfaces pioneering autonomous and personalized diagnostics

2.1 Piezoelectric effect and mechanism

The piezoelectric effect is a fascinating phenomenon in physics and materials science that describes the ability of certain materials to generate an electric charge when subjected to mechanical stress.^[45,46] Discovered by brothers Pierre and Jacques Curie in 1880, this effect has since been widely studied and applied.^[47,48] The piezoelectric effect predominantly occurs in materials with noncentrosymmetric crystal structures, such as quartz, lead zirconate titanate (PZT), and PVDF.^[49,50] When these materials experience mechanical stress, their crystal lattices deform, leading to a relative displacement of the centers of positive and negative charges, thereby forming electric dipoles.^[45,51] This separation of charges generates a potential difference across the material, resulting in a measurable voltage.^[15,52] It is important to note that the piezoelectric effect is reversible.^[51,53] This means that such materials can also undergo mechanical deformation when an external electric field is applied—a property known as the inverse piezoelectric effect.^[54,55] The microscopic mechanism underlying the piezoelectric effect is intimately linked to the crystal structure of the material.^[56,57] In noncentrosymmetric crystals, the distribution of positive and negative charges is inherently asymmetric.^[58,59] The direct piezoelectric effect is essentially the process of converting mechanical energy into electrical energy. When an external force is applied, the deformation of the lattice further amplifies this asymmetry, and the polarization strength of the crystal is:

where $d$ is the piezoelectric constant, the unit is C/N, $\sigma$ is the stress, the unit is N/m².^[60,61] This polarization creates an electric field, which can generate an electric current if the material is connected to an external circuit.^[62,63] Conversely, when an electric field is applied, the dipoles within the material realign themselves, resulting in mechanical deformation.^[62,64] This bidirectional energy conversion capability makes piezoelectric materials highly versatile for a wide range of applications.

The piezoelectric effect has important practical applications across various fields. In sensing and actuation, piezoelectric materials are utilized in devices such as accelerometers,^{[65–66–67]} pressure sensors,^{[68–69–70]} and ultrasonic transducers.^{[71–72–73–74]} In energy harvesting, they are employed in nanogenerators to convert mechanical energy generated by vibrations, footsteps, or other movements into electrical energy.^[75,76] Within the medical field, piezoelectric materials play a critical role in ultrasound imaging,^{[77–78–79]} piezoelectric motors,^{[80–81–82]} and implantable devices.^{[83–84–85]} Additionally, they are used in acoustic devices such as speakers,^[86,87] microphones,^[88,89] and sonar systems.^[90,91] The ability to convert mechanical energy into electrical energy and vice versa makes piezoelectric materials indispensable in modern technology. In the realm of biomedical diagnostics, the piezoelectric effect and devices based on piezoelectric materials, such as PENG, have shown remarkable potential. A PENG is a device that can convert mechanical energy (such as vibration, pressure, or movement) into electrical energy.^[92] In biomedical applications, PENG can harvest energy from physiological activities of the human body (such as heartbeat, breathing, or blood flow) and convert it into electrical signals.^[92,93] This capability allows PENG to develop self-powered medical devices, PENG can be integrated into wearable devices for real-time monitoring of vital signs such as heart rate (HR),^[10,37] blood pressure,^[29,94] or respiratory rate.^{[95–96–97]} Moreover, PENG can be used in implantable devices to detect abnormalities in organ function.^[10,98] The advantages of PENG in biomedical diagnostics lie in their high sensitivity, compact size, and the absence of an external power supply. These features make PENG highly suitable for continuous and noninvasive health monitoring. For example, PENG can harvest energy from the natural movements of the human body,^[99] thereby reducing dependence on batteries, extending the life of devices, and improving patient comfort.^[11] Additionally, PENG can be combined with other sensing technologies to detect biomarkers^[100,101] or environmental parameters,^[102] thus supporting early disease diagnosis and personalized treatment.

2.2 Overview of piezoelectric materials

Piezoelectric materials are fascinating substances with unique properties: they can generate an electric charge in response to mechanical stress or, conversely, deform when subjected to an electric field.^[62] This dual functionality makes them essential in a variety of scientific, industrial, and technological applications. The Curie brothers first observed the piezoelectric effect in crystals such as quartz in the late 19th century, where mechanical stress leads to the generation of an electric charge.^[103,104] Since then, researchers have discovered and synthesized a number of materials with piezoelectric properties, greatly expanding their uses.

One of the most notable features of piezoelectric materials is their ability to convert mechanical energy into electrical energy and vice versa.^[105] This property is used in a wide range of devices, such as piezoelectric sensors,^[106,107] actuators,^[80,82] transducers,^[54,108] and even energy harvesters.^[109,110] Piezoelectric sensors are often used in pressure sensors, accelerometers, and ultrasonic devices because of their high sensitivity and fast response time.^[111] Piezoelectric actuators, on the other hand, are used in precision positioning systems, valves, and switches.^[80] Piezoelectric materials are able to deform with extreme precision and speed, which makes them invaluable in applications where fine control is crucial. In the field of energy harvesting, piezoelectric materials can convert ambient vibrations and mechanical motion into electrical energy.^[112] This technology is particularly useful for powering small electronic devices and sensors in remote or hard-to-reach places.^[113] Piezoelectric materials come in a variety of forms, including organic, inorganic, and composite materials (Figure 1). Each type has its own unique properties and characteristics that make it suitable for different applications, as shown in Table 1. For example, PZT is a widely used ceramic material known for its high piezoelectric coefficient and excellent electromechanical coupling.^{[114–115–116]} PVDF is a popular piezoelectric polymer that is flexible and biocompatible, making it ideal for wearable devices, medical sensors, and energy harvesting applications.^{[114,117,118]} In recent years, researchers have also explored the potential of new types of materials, such as two-dimensional (2D) materials (eg., graphene),^[119] organic crystals,^[120,121] and nanowires^[122,123] with enhanced piezoelectric properties. These advances have opened up new possibilities for developing more efficient and versatile piezoelectric devices. Despite their many advantages, piezoelectric materials also have some limitations. For example, they are sensitive to temperature changes,^[124] humidity,^[125] and mechanical fatigue,^[126,127] which can affect their performance over time. Researchers are actively working to address these challenges through material design,^[128] processing techniques, and device optimization.^[129] In summary, piezoelectric materials play a vital role in modern technology and continue to drive innovation in a variety of fields. Their unique ability to convert mechanical energy into electrical energy and electrical energy into mechanical energy makes them indispensable in a wide range of applications, from sensors and actuators to energy harvesting devices. As research in this field progresses, we can expect to see even more exciting developments and applications of piezoelectric materials in the future.

2.3 Outlook on piezoelectric materials

Fueled by advancements in materials science, nanotechnology, and interdisciplinary innovation, piezoelectric materials are poised to play a transformative role in the evolution of energy harvesting, sensing, and biomedical technologies. As the demand for sustainable, self-powered systems intensifies across various industries, the development of next-generation piezoelectric materials will focus on overcoming existing limitations while unlocking new capabilities. Key trends shaping the future of this field include the adoption of lead-free and biocompatible materials, the integration of hybrid and composite systems, and the convergence of piezoelectrics with emerging domains such as flexible electronics and AI.

3.1 Fabrication methods

The performance and scalability of PENG depend on fabrication methods tailored to material properties and applications. Table 2 summarizes key techniques, including sputtering, sol–gel spin coating, CVD, hydrothermal synthesis, electrospinning, nanoimprint lithography (NIL), solution casting, 3D printing, and poling. Each method offers unique advantages: sputtering and CVD produce high-quality films, hydrothermal synthesis and sol–gel coating enable cost-effective processing, and electrospinning and NIL enhance flexibility and performance. While solution casting and 3D printing offer design versatility, poling is essential for optimizing piezoelectric properties. The selection of a fabrication technique depends on the specific application and performance requirements.

3.1.1 Sputtering/physical vapor deposition

Sputtering, a form of physical vapor deposition (PVD), is an efficient and versatile method for fabricating PENG (Figure 2A). This technique involves the ejection of atoms from a solid target material through the impact of high-energy ions within a vacuum chamber.^[201] These ejected atoms are subsequently deposited onto a substrate, forming a thin, uniform film.^[201] Sputtering is particularly suitable for PENG fabrication due to its ability to produce high-quality, dense, and adherent films with precise control over thickness and composition.^[202] This method is extensively employed for the deposition of piezoelectric materials such as ZnO,^[203] aluminum nitride (AlN),^[204] and PZT,^[205] as well as conductive electrodes including gold (Au)^[206] and indium tin oxide (ITO).^[207] Consequently, sputtering has become a cornerstone technology for the fabrication of efficient and durable PENG. Its compatibility with flexible substrates such as polyethylene terephthalate (PET) and PDMS further facilitates the development of wearable and implantable devices, broadening the potential applications of PENG in healthcare, IoT, and environmental monitoring.^[208]

The advantages of sputtering for PENG fabrication are substantial. It offers high precision in controlling film thickness at the nanoscale, ensuring optimal piezoelectric performance. The process is versatile, capable of depositing a wide range of materials, and is scalable for industrial production. Additionally, sputtering can be performed at low temperatures, making it suitable for temperature-sensitive substrates. Nevertheless, the method is not without its challenges. The high cost of equipment and target materials, the complexity of maintaining a vacuum environment, and the need for precise control of process parameters can present significant barriers.^[209] Moreover, sputtered films may develop internal stresses that impact device performance, and deposition rates can be slower compared to other methods, such as spin coating.^[210] Despite these drawbacks, ongoing advancements in sputtering technology, including the development of environmentally friendly materials and hybrid manufacturing techniques, are addressing these limitations and enhancing its applicability.

3.2 Structural innovations

Structural innovations in PENG have revolutionized their design, enabling significant advancements in efficiency, adaptability, and integration across diverse applications. By reimagining device architectures, researchers have addressed long-standing challenges such as limited energy conversion efficiency, material brittleness, and scalability. Advanced layered and nanostructured designs have markedly improved the performance of PENG by optimizing their structural and functional properties. Vertical nanowire arrays, such as oriented ZnO or GaN nanowires grown on flexible substrates, enhance surface area and strain sensitivity, thereby increasing charge separation under compressive stress and producing higher output voltages.^[255] Electrospun nanofibers, particularly from piezoelectric polymers like PVDF or PVDF-BaTiO₃ composites, form porous, oriented mats that improve strain distribution and β-phase crystallinity, resulting in higher piezoelectric coefficients.^[256] Core-shell structures, where a piezoelectric core is coated with a conductive shell (eg., graphene or silver nanoparticles), further enhance charge collection efficiency and reduce leakage current.^[257] Collectively, these innovative designs have significantly improved the energy conversion efficiency, mechanical adaptability, and overall performance of PENG, making them highly suitable for applications in wearable electronics, energy harvesting, and sensing technologies.

Flexible and stretchable architectures have significantly advanced the development of PENG, transforming them into highly adaptable and durable energy-harvesting devices. The implementation of wavy and kirigami patterns, achieved through prestrained substrates or laser-cut designs, allows PENG to endure strains exceeding 50% without performance degradation.^[258] This capability is particularly advantageous for wearable sensors designed to monitor joint motion. Textile-integrated PENG, which incorporates piezoelectric fibers such as PVDF or nylon 11 into fabrics, enables energy harvesting from body motion while maintaining breathability and comfort, thereby seamlessly blending functionality with wearability.^[183] Additionally, island-bridge electrode designs utilize rigid piezoelectric “islands” connected by stretchable serpentine electrodes, ensuring consistent performance even under extreme deformations.^[259] These innovations in flexible and stretchable architecture significantly broaden the potential applications of PENG, facilitating their integration into wearable electronics, soft robotics, and other applications that demand high mechanical adaptability and durability.

Hybrid and multilayer systems significantly enhance the performance and versatility of PENG by integrating multiple energy harvesting mechanisms and optimizing structural designs. Piezoelectric-triboelectric hybrids, such as PVDF and PDMS bilayer devices, combine PENG with triboelectric nanogenerators (TENG) to simultaneously harvest energy from mechanical strain and friction, thereby substantially increasing power density.^[260] Multilayer stacks, composed of alternating piezoelectric and electrode layers, amplify charge generation by synchronizing the stress between multiple active layers, resulting in enhanced overall efficiency.^[261] Furthermore, 3D-printed architecture enables the creation of complex geometries, such as honeycomb or lattice structures, which optimize stress distribution and resonant frequency for specific mechanical inputs.^[262] These advancements in hybrid and multilayer systems expand the capabilities of PENG, making them more efficient and adaptable to a broad spectrum of applications, including wearable electronics and ambient energy harvesting.

Biomimetic and nature-inspired designs offer innovative approaches to enhance the functionality and integration of PENG. Bone-mimicking composites, which replicate the hierarchical structure of bones using materials such as hydroxyapatite and polymers, improve biocompatibility and mechanical elasticity, making them particularly suitable for implantable PENG.^[263] Leaf vein-inspired fractal or branched electrode patterns optimize charge collection efficiency in large-area devices by emulating the efficient nutrient distribution systems of plant leaves.^[264] Additionally, mussel-inspired adhesives, in conjunction with dopamine-modified surfaces, enable PENG to adhere firmly to biological tissues such as skin or organs, ensuring stable and long-term monitoring capabilities.^[265] These nature-inspired designs not only enhance the performance and durability of PENG but also expand their potential applications in biomedical devices, wearable sensors, and other fields requiring seamless integration with biological systems.

Advanced electrode engineering has significantly contributed to enhancing the performance, durability, and versatility of PENG. Interdigitated electrodes with a comb-like pattern maximize the effective area for charge generation, thereby substantially increasing the output current of thin-film PENG.^[266] Transparent electrodes, composed of materials such as ITO or graphene, facilitate the development of transparent PENG, which can be seamlessly integrated into applications like touch screens and smart windows.^[267] Moreover, self-healing electrodes, utilizing materials such as liquid metals (eg., eutectic gallium-indium) or dynamic polymers, possess the capability to autonomously repair cracks induced by cyclic stress, thereby extending the operational lifespan of PENG.^[268] These innovations in electrode design not only enhance the efficiency and reliability of PENG but also broaden their applicability in transparent electronics, wearable devices, and environments demanding long-term durability.

Despite substantial advancements, PENG continues to face several challenges that must be addressed to fully realize their potential. Scalability remains a significant issue, as many nanostructure designs, such as vertical nanowires, present difficulties in mass production. Durability is another concern, with repeated stress cycles potentially degrading the polymer-ceramic interface in composites, thereby limiting their long-term performance. Additionally, integrating PENG with energy storage systems, such as supercapacitors or batteries, to ensure a stable power supply remains a complex challenge that necessitates further innovation. Looking ahead, emerging trends offer promising opportunities for the future development of PENG. These include four-dimensional (4D)-printed PENG with shape-morphing capabilities that can adapt to dynamic environments, AI-optimized designs that leverage ML to predict ideal geometries for specific applications, and the exploration of quantum piezoelectricity in 2D materials such as molybdenum disulfide (MoS₂) for ultrasensitive nanogenerators. By addressing these current challenges and embracing these advanced trends, the field of PENG can continue to progress, enabling transformative applications in energy harvesting, wearable electronics, and beyond.

3.3 Challenges in miniaturization

The miniaturization of PENG offers both compelling opportunities and formidable challenges, as reducing the size of these devices while maintaining or enhancing their performance is crucial for applications in wearable electronics, biomedical devices, and IoT sensors. One of the primary challenges is sustaining high energy output in smaller devices. As PENG is miniaturized, the active piezoelectric material volume decreases, which results in diminished power generation.^[182] To address this issue, researchers are investigating advanced nanostructuring techniques, such as nanowires, nanorods, and nanocomposites, to maximize the surface area and strain sensitivity of miniaturized PENG. However, achieving uniform and precise nanostructuring at such a diminutive scale remains technically challenging and often necessitates complex fabrication methods, including NIL or CVD.^[269]

Another significant challenge is the integration of PENG with other components in miniaturized systems. PENG must be seamlessly incorporated into compact devices without compromising their functionality or the performance of other components, such as sensors, processors, or energy storage units. This necessitates innovative design and packaging techniques to ensure efficient energy transfer and mechanical stability. Additionally, the mechanical durability of miniaturized PENG is a concern, as smaller devices are more susceptible to damage from repeated mechanical stress or environmental factors. The development of flexible and robust materials, such as polymer-based composites or hybrid structures, is essential to address this limitation and ensure long-term reliability.

Scalability and cost also pose significant barriers to the widespread adoption of miniaturized PENG. Many of the advanced manufacturing techniques required for miniaturization, such as electron beam lithography or atomic layer deposition, are expensive and not easily scalable for mass production.^[270] Researchers are actively exploring cost-effective alternatives, such as roll-to-roll printing and 3D printing, but these approaches often involve trade-offs in resolution and material properties.^[271] Despite these challenges, the potential of miniaturized PENG to enable self-powered, portable, and implantable devices continues to drive innovation in the field.

4.1 Cardiovascular

PENGs have emerged as a transformative tool in cardiovascular monitoring, enabling real-time tracking of HR, blood pressure, and vascular health by harvesting mechanical energy from arterial pulsations and heartbeats. The development of sensors capable of accurately detecting micropressure changes in vivo is critical for monitoring chronic pressure-related conditions such as vascular occlusion, arterial hypertension, and brain injury. However, traditional pressure sensors face limitations in detecting micropressures below 1 kPa over extended periods due to poor flexibility and biocompatibility, particularly in implantable applications. To address these challenges, researchers have proposed an innovative approach using ultrathin, flexible smart patches based on piezoelectric AIN (Figure 4A).^[272] These patches, integrated onto the extraluminal surface of artificial blood vessels, exhibit high sensitivity and biocompatibility, enabling real-time monitoring of hemodynamic parameters without compromising the mechanical properties of the graft. Experimental results demonstrate the sensors’ stable response to flow changes, highlighting their potential for continuous monitoring and optimizing patient treatment (Figure 4B).^[272] Additionally, the innovative PVDF/hydroxylamine hydrochloride (HHE) organic piezoelectric nanofibers (OPNs) sensor has been successfully implanted in living pigs to monitor micropressure changes within and around the cardiovascular wall, demonstrating its feasibility for real-time monitoring under various physiological conditions (Figure 4C).^[273] These advancements offer new possibilities for enhancing vascular health monitoring and early detection of complications.

In the field of physiological signal detection, accurately capturing sound signals emitted by the human body—such as breathing, heartbeat, and vascular sounds—poses significant challenges due to their complexity. While microelectromechanical system (MEMS)-based sensors provide high accuracy, their manufacturing processes limit their flexibility and compliance. To overcome these limitations, researchers have developed novel sensors using piezoelectric electret technology, which achieve higher sensitivity and compliance (Figure 4D).^[274] These sensors are integrated into flexible patches, leveraging unique structures and materials to ensure accurate detection of physiological signals while maintaining comfort and usability. By strategically placing these sensors on the body, comprehensive monitoring of vital signs and physiological parameters can be achieved, enhancing diagnostic capabilities and enabling early intervention for cardiovascular and respiratory diseases.

Implantable pulse sensors play a critical role in monitoring hemodynamic parameters postsurgery, providing real-time data on cardiovascular health and hemodynamics. However, conventional rigid sensors suffer from mechanical incompatibility and long-term stability issues, prompting researchers to explore adaptive sensors made from degradable materials or optimized structures. An innovative approach involves integrating piezoelectric sensors with biomimetic conformal sheaths to create an implantable vascular electronic system for wireless hemodynamic monitoring (Figure 4E).^[275] This system combines flexible piezoelectric sensors, stretchable sheaths, and wireless modules to enable real-time monitoring and data transmission without impeding arterial growth. Utilizing highly aligned PVDF nanofiber membranes and elastic nanofiber PU tubes, the system sensitively and stably monitors hemodynamic parameters while adapting to dynamic changes in arterial geometry. Alternatively, all-in-one piezoelectric vascular grafts feature layered nanofibrous scaffolds with embedded electrodes, achieving native tissue-like mechanical behavior while enabling real-time hemodynamic assessment.^[276] These grafts demonstrate rapid endothelial integration and exceptional biocompatibility with minimal blood cell damage. Both solutions transcend traditional rigidity issues, the former through stretchable interfacial design, the latter via structural biomimicry, and operate without external power sources.^[276] By facilitating continuous physiological tracking and early detection of vascular complications, they establish new paradigms for patient-specific cardiovascular management. Validated through physiological testing, these technologies converge toward intelligent implants capable of supporting precision interventions across diverse clinical scenarios.

Two millennia ago, pulse diagnosis served as the cornerstone of ancient Chinese medicine for diagnosing cardiovascular diseases. Today, the field of medical technology has undergone a transformative evolution, shifting toward the development of portable, wearable systems capable of continuous monitoring of vital signs, particularly arterial pulse monitoring for blood pressure assessment. Achieving accurate wearable blood pressure monitoring, however, presents significant challenges, especially when utilizing piezoelectric sensors. Known for their dynamic response characteristics and high fidelity, piezoelectric sensors have played a pivotal role in advancing continuous blood pressure monitoring technology. Yet, issues such as time synchronization errors, sensor positioning discrepancies, and variations in piezoelectric response have raised concerns about their reliability in blood pressure monitoring. To address these challenges, recent studies have extensively investigated the piezoelectric response of arterial pulses across functional layers of varying thicknesses (Figure 5A).^[277] By establishing a direct correlation between blood pressure waves and piezoelectric arterial pulse waves, the feasibility of blood pressure monitoring using a single piezoelectric sensor has been demonstrated (Figure 5B).^[277] This breakthrough not only deepens the understanding of arterial pulse dynamics but also paves the way for the development of accurate and convenient wearable blood pressure monitoring devices.

The importance of continuous blood pressure monitoring is particularly critical in the context of combating hypertension, a global health issue affecting millions and a leading cause of cardiovascular diseases and related mortality. With the growing demand for noninvasive, continuous arterial pressure monitoring devices, the development of wearable sensors that seamlessly integrate into daily life has become a top priority. The wearable piezoelectric blood pressure sensor (WPBPS) exemplifies such innovation, designed for continuous noninvasive arterial pressure monitoring (Figure 5C).^[278] With high sensitivity and rapid response times, the sensor is ingeniously embedded into a watch band, showcasing the seamless integration of cutting-edge technology with practical healthcare solutions. Through a wireless communication system, real-time arterial pulse data is transmitted to portable devices, enabling continuous blood pressure monitoring without the discomfort associated with traditional measurement techniques. Furthermore, researchers are advancing sensor technology by exploring the role of elastic media in enhancing pulse wave signal transmission to optimize sensing performance and accuracy (Figure 5D).^[279] In another breakthrough, a wearable sensor utilizing heterogeneous graded piezoelectric composites has achieved accuracy comparable to commercial sphygmomanometers. This sensor not only supports continuous blood pressure monitoring but also provides hemodynamic parameters essential for comprehensive cardiac function analysis (Figure 5E).^[280] By combining innovation with precision, this sensor heralds a new era of personalized medical systems, offering a powerful tool for early diagnosis and intervention in cardiovascular diseases.

Moreover, the integration of cutting-edge technologies holds immense potential. For instance, the closed-loop renal denervation system combines piezoelectric film sensors with photothermal ablation technology, demonstrating the possibility of targeted and effective hypertension treatment by regulating renal sympathetic nerve activity (Figure 5F).^[281] This integrated approach not only provides a novel strategy for managing refractory hypertension but also opens new avenues for treating chronic diseases related to sympathetic nerve activity, underscoring the transformative potential of technology in healthcare.

Wearable piezoelectric blood pressure sensors represent a significant advancement in preclinical continuous noninvasive arterial pressure monitoring, addressing longstanding accuracy challenges through material innovation and signal processing. The first approach employs a flexible piezoelectric sensor with optimized sensitivity and dynamic response, coupled with a linear regression transfer function to directly convert mechanical signals into clinically valid systolic and diastolic pressures.^[278] Rigorous clinical validation across 35 subjects demonstrated exceptional alignment with commercial, enabling integration into wrist-worn devices for real-world cardiovascular monitoring. A second strategy utilizes a flexible piezocomposite ultrasonic sensor featuring PZT-5A/PDMS anisotropic composites and silver nanowire electrodes.^[282] This design achieves nonocclusive vessel wall motion tracking through optimized acoustic impedance matching, capturing full arterial waveforms without calibration. Preliminary human trials confirmed accurate continuous pressure waveform acquisition at the ulnar artery, correlating strongly with clinical ultrasound probes and conventional monitors. Together, these PENG-based approaches, leveraging direct mechanical transduction and ultrasonic kinematics, establish robust preclinical frameworks for wearable blood pressure management, overcoming critical limitations in signal fidelity, calibration dependency, and long-term wearability while demonstrating viable pathways toward clinical deployment.

In summary, the convergence of advanced sensor technology, innovative materials, and strategic design is revolutionizing the field of physiological monitoring. From detecting micropressure changes within the body to monitoring vascular grafts and capturing critical physiological signals, these advancements provide powerful tools for enhancing diagnostic capabilities and enabling real-time insights into cardiovascular health. By leveraging piezoelectric materials, flexible sensors, and wireless communication technologies, researchers are developing more effective and patient-centric medical solutions, paving the way for the future of precision medicine. From ancient pulse diagnosis to modern wearable piezoelectric sensors, blood pressure monitoring technology has undergone a revolutionary transformation. Through the integration of innovative materials, advanced sensor technologies, and wireless communication systems, researchers are driving the advancement of personalized medicine, offering robust support for the early diagnosis, continuous monitoring, and precise treatment of cardiovascular diseases. These technological breakthroughs not only enhance the efficiency and quality of healthcare but also bring new hope for improving global cardiovascular health, marking a monumental leap from traditional to modern medical technology.

4.2 Respiratory

PENG have emerged as a powerful tool for respiratory monitoring, capable of capturing the biomechanical energy generated by chest movements during breathing to assess critical parameters such as respiratory rate, tidal volume, and obstruction status. As a frontier in healthcare and physiological monitoring, respiratory function measurement provides vital insights into overall health and aids in the diagnosis of lung diseases. While respiratory rate serves as a key biomarker, the need for comprehensive data on respiratory flow and volume underscores the urgent demand for advanced wearable devices. In this context, self-powered multifunctional sensor technologies have gained prominence. For instance, a flexible hybrid nanofiber sensor based on a PAN/TMAB composite nanofiber membrane (Figure 6A) exhibits dual piezoelectric and pyroelectric properties, enabling the accurate detection of various physiological signals, including elbow flexion angle, foot posture, and respiratory status.^[283] Its versatility extends beyond human health monitoring to energy conversion and human–computer interaction, setting a new benchmark for wearable sensor technology.

Further advancements are exemplified by the development of all-organic, degradable piezoelectric force sensors based on amino acid crystals (Figure 6B),^[192] marking a significant milestone in biomedical applications. Designed for dynamic physiological monitoring in model animals, these sensors are biocompatible and fully biodegradable, heralding a new era in medical sensor design. Through in vivo testing in adult Sprague–Dawley rats, these sensors have demonstrated superior capabilities in capturing muscle contractions and respiratory activity, outperforming existing nanogenerators and showcasing immense potential for clinical applications.

Major breakthrough in energy harvesting and physiological monitoring. When integrated into a smart mask, these sensors enable continuous, self-powered respiratory status monitoring, offering a critical tool for disease prevention and personalized healthcare. Their ability to distinguish between normal and rapid breathing patterns through temperature fluctuations within the mask highlights their significance in real-time health monitoring applications.

Finally, the integration of piezoelectric/triboelectric hybrid nanogenerators (PT-NGs) (Figure 6D) provides a simple yet efficient solution for energy conversion and wearable sensor technology.^[284] By combining piezoelectric charge generation with triboelectric charging, this composite film-based device excels in energy conversion efficiency and is ideal for monitoring finger movements, gestures, and breathing patterns. When placed externally on a mask, these sensors can accurately monitor breathing rate and patterns, offering valuable insights into respiratory health and facilitating timely health alerts and interventions.

Additionally, the development of fully 3D-printed thermos PENG utilizing cellulose nanocrystals (Figure 6C) has further propelled progress in this field.^[285] These state-of-the-art sensors can autonomously detect cardiac pulses and respiratory activity, representing a new class of self-powered, wearable biomedical devices for continuous, noninvasive health monitoring and potential human–machine interface applications.

The integration of innovative technologies into wearable devices for monitoring metabolic and respiratory functions has driven significant advancements in this field. Among these, wearable piezoelectric airflow sensors (WPATs) offer a novel, cost-effective, and accurate solution for tracking metabolic and respiratory activities (Figure 7A).^[286] A notable design, the double-layer PLLA BS (PLLA2BS), demonstrates enhanced piezoelectric signals at varying air velocities compared to single-layer PLLA BS. This design significantly improves airflow sensing capabilities by stacking 2 piezoelectric PLLA films at a specific cutting angle. Finite element simulations in ABAQUS support the hypothesis that respiratory airflow generates a pressure differential across the PLLA2BS, inducing the piezoelectric effect. Variations in airflow rate further amplify this effect, directly influencing piezoelectric signal generation.

Innovative strategies, such as fully 3D-printed manufacturing methods, have revolutionized the production of wearable devices (Figure 7B).^[285] For instance, fully 3D-printed nanogenerators simplify production steps and reduce equipment requirements by utilizing ink as both the active thermos-piezoelectric material and electrode. Conductive carbon nanotubes (CNTs) embedded in the polymer matrix enhance electrode conductivity and optimize the printing process. This layer-by-layer printing strategy enables the creation of complex, multilayer devices suitable for diverse applications, including respiratory monitoring.

Additionally, the thermal stretching technique for embedding transition metal dichalcogenides into fluoropolymer fibers offers a novel approach for noninvasive cardiovascular signal monitoring (Figure 7C).^[287] By quantitatively measuring arterial pressure changes at different skin locations, this technology assesses cardiovascular health. Simultaneously, integrating piezoelectric fibers into respiratory monitoring systems allows for the concurrent capture of pulse and respiratory waveforms (Figure 7D).^[287] Signal processing techniques, combined with low-pass and band-pass filters, effectively separate vital sign data, providing detailed insights into physiological responses during the respiratory cycle.

In the realm of sustainable technology, PENG fabricated from household crab shell waste and PVDF demonstrates the potential for environmentally friendly and cost-effective sensor production (Figure 7E).^[288] Voltage-time graphs depict various respiratory states, such as slow and fast breathing, showcasing the device’s ability to detect and distinguish different respiratory conditions. This application not only advances breathing detection technology but also offers a versatile and eco-friendly solution for monitoring respiratory activity across diverse environments.

Piezoelectric sensors demonstrate versatile preclinical utility in respiratory monitoring, spanning from home-based sleep studies to critical care applications. In residential settings, stretchable piezoelectric sensors effectively tracked respiration across all age groups, noninvasively identifying sleep patterns including stable breathing, apnea events, and age-dependent respiratory variations.^[289] A hospital-deployable piezoelectric system was developed for continuous systemic inflammatory response syndrome screening in COVID-19 patients.^[290] This noninvasive monitor combined under-mattress respiratory sensing with fingertip pulse detection, achieved high sensitivity and high negative predictive value in 29 hospitalized patients monitored around the clock, validating its potential for preliminary SIRS assessment in clinical environments.

By focusing on advancements in respiratory detection applications, these developments pave the way for enhanced medical monitoring, disease prevention, and personalized interventions, highlighting the immense potential of wearable sensor technology in improving human health and well-being. These innovations not only propel medical technology forward but also provide robust support for the future of precision medicine and personalized health management.

4.3 Muscle and motion

PENG have the capability to convert mechanical strains generated by muscle contractions into electrical signals, enabling the tracking of muscle activity, gait, and rehabilitation progress. With growing concerns over work-related upper limb musculoskeletal disorders (MSDs) and neuromuscular diseases, the development of innovative monitoring and response solutions has become increasingly critical. MSDs, particularly neck pain and shoulder fatigue, are highly prevalent in the European population, underscoring the urgent need for continuous monitoring systems to prevent and rehabilitate such conditions. However, current wearable sensor systems face limitations, including complex structures and insufficient data acquisition, which hinder their practical application. To address these challenges, researchers are advancing new sensor technologies aimed at revolutionizing monitoring capabilities across various health domains.

In the realm of neuromuscular diseases, such as amyotrophic lateral sclerosis (ALS), the impairment of motor skills and communication abilities highlights the necessity for advanced monitoring systems. ALS patients often struggle with fine motor tasks and speech expression, necessitating innovative solutions to facilitate communication and task completion. The introduction of flexible facial code extrapolation sensors (cFaCES) and highly anisotropic piezoelectric network composite (HAPNC) sensors offers groundbreaking opportunities for tracking dynamic facial skin strain and monitoring joint movement patterns (Figure 8A, B).^[291,292] These sensors provide a noninvasive and efficient means of tracking physiological changes and movement disorders, enabling ALS patients to communicate more effectively and engage more easily in daily activities.

Furthermore, piezoelectric capacitive flexible sensors developed through laser direct printing methods, as well as sensors based on single-crystal III-nitride films, have expanded the application of innovative sensing technologies. The piezoelectric capacitive sensor features a hybrid microstructure and an ion gel dielectric layer (Figure 8C),^[293] offering high sensitivity and stability, making it suitable for monitoring physiological signals such as throat movement, speech, facial gestures, and pulse. Meanwhile, the flexible piezoelectric eye movement sensor array (F-PEMSA) based on III-nitride films provides a comfortable and noninvasive method for eye movement tracking (Figure 8D),^[294] demonstrating excellent sensitivity and repeatability. These technological advancements pave the way for practical applications in health monitoring, facilitating continuous and safe monitoring of eye movements and breathing patterns.

The integration of state-of-the-art sensor technologies into wearable devices represents a paradigm shift in the continuous and unobtrusive monitoring of physiological activities. Li et al.^[295] proposed an electrospun PVDF piezoelectric nanofibre membrane with functional modulation of CNT and barium titanate (BTO) to construct wearable piezoelectric tactile sensors with self-supply capability, fast response, high sensitivity and good durability, and successfully applied to human body multisite motion monitoring and recognition, which provides a new solution with practical prospects for flexible health sensing electronic devices (Figure 9A, B). Figure 9C showcases a flexible piezoelectric sensor designed to monitor laryngeal motion by detecting skin deformation resulting from hyoid bone displacement.^[296] Fabricated using AIN on a Kapton polyimide substrate, this smart patch offers critical insights into swallowing kinematics, enabling the quantitative assessment of dysphagia and related clinical conditions. The sensor’s compact, lightweight, and biocompatible design ensures conformal integration with the neck’s curved anatomy, facilitating uninterrupted monitoring of laryngeal dynamics without impeding natural swallowing functions (Figure 9D).^[296] Equipped with Bluetooth connectivity for wireless data transmission to smartphones, this system represents a significant advancement in real-time diagnostic capabilities, providing clinicians with actionable data for timely therapeutic interventions.

Figure 9E highlights a novel motion-sensing device that exploits the polar β-phase nucleation characteristics of electroactive polymers.^[297] By incorporating TiO₂ nanoparticles into poly(vinylidene fluoride-co-hexafluoropropylene) films, the device achieves enhanced β-phase crystallization, resulting in superior remnant polarization and energy density. This configuration enables ultra-low frequency detection, making it highly effective for monitoring a broad spectrum of voluntary motions, ranging from joint movements to fine motor actions such as finger tapping. The device’s ability to accurately track activities from ambulation to running demonstrates its versatility in applications spanning smart wearables, sports biomechanics, and medical diagnostics.

The convergence of these advanced sensing technologies not only enhances the quality of life for individuals with specific health conditions but also expands the scope of health monitoring applications, underscoring the pivotal role of sensor innovation in advancing proactive healthcare management. By synergizing breakthroughs in materials science, microfabrication techniques, and signal processing algorithms, researchers are driving the development of wearable devices that are more efficient, precise, and sustainable. These advancements provide a robust foundation for personalized medicine and continuous health monitoring, ultimately contributing to improved patient outcomes and preventive healthcare strategies.

4.4 Metabolic

PENGs are emerging as a transformative platform for indirect metabolic monitoring, leveraging their ability to transduce mechanical or pressure fluctuations associated with biochemical processes into quantifiable electrical signals. Conventional metabolic assessment techniques, such as maximal oxygen uptake testing and blood lactate analysis, are often constrained by their invasiveness, operational complexity, and interference with physical activity. To overcome these limitations, a novel biosensor utilizing PVDF/T-ZnO composite piezoelectric materials has been developed (Figure 10A).^[298] This device, integrated onto human skin or tissues via a flexible substrate, exploits the piezoelectric effect to simultaneously capture biomechanical signals and metabolic fluctuations, enabling real-time dynamic monitoring of the maximal lactate steady state (MLSS) (Figure 10B).^[298] MLSS, recognized as the gold standard for evaluating aerobic endurance, plays a critical role in optimizing athletic training regimens and designing rehabilitation protocols for cardiovascular patients. Furthermore, lactate, a pivotal metabolic marker in the tumor microenvironment, exhibits concentration abnormalities that reflect the metabolic reprogramming of cancer cells. The PENG-based sensing system offers a noninvasive approach for cancer prognosis by detecting localized tissue stiffness variations induced by lactate accumulation, particularly for early detection of solid tumors such as breast and liver carcinomas.

Additionally, wearable experiments have elucidated the correlation between minute ventilation and metabolic rate (Figure 10C),^[286] underscoring the potential of sensor technology to deepen our understanding of human metabolic dynamics. An advanced implantable device utilizing ultrasound-mediated data transmission presents a promising solution for monitoring pH and lactate levels in soft tissues, which is critical for postoperative care and disease progression evaluation. The integration of electrochemical sensors into implantable systems (Figure 10D) has the potential to revolutionize soft tissue parameter assessment, enabling home-based monitoring and improving patient outcomes, particularly in scenarios where hospitalization is impractical.^[299] By seamlessly integrating these cutting-edge technologies—from MLSS-monitoring biosensors to ultrasound-enabled implantable devices (Figure 10E)—a comprehensive framework is established to advance healthcare practices, enhance sports performance analytics, and facilitate remote patient management.^[299] This convergence of innovations paves the way for more efficient, personalized, and noninvasive health monitoring solutions, ultimately driving progress in precision medicine and proactive healthcare delivery.

4.5 Neural and brain activity

PENG have demonstrated the potential to detect neural oscillations and changes in intracranial pressure, offering insights into neural and brain activity. However, challenges related to sensitivity and invasiveness remain. By integrating ultrasonic energy transmission, piezoelectric material engineering, and targeted biological delivery technologies, researchers have developed a range of wireless, noninvasive, or minimally invasive diagnostic and therapeutic platforms. These innovations provide novel solutions for deep brain stimulation, interventions for neurodegenerative diseases, and obesity treatment.

Conventional DBS systems, which rely on implanted electrodes, are hindered by issues such as surgical trauma, electrode corrosion, and charge diffusion. To address these limitations, a novel piezoelectric ultrasonic energy harvesting device utilizing Sm-doped PMN-PT single crystals has been developed (Figure 11A).^[300] This device leverages the piezoelectric response to ultrasound, efficiently converting externally emitted ultrasonic energy into electrical power. Upon implantation into the periaqueductal gray matter of rat midbrains, the device instantaneously activates analgesia-related neural circuits. Behavioral experiments demonstrate that wireless stimulation significantly alleviates pain responses without inducing tissue damage (Figure 11B).^[300] Complementarily, regenerative strategies employ hybrid nanomaterials that attach to neural stem cells, functioning as membrane-integrated piezoelectric actuators. Under ultrasonic excitation, these materials generate electrical cues that accelerate neuronal differentiation and maturation through calcium-mediated signaling pathways.^[301] When transplanted into injured brain tissue, such engineered constructs promote substantial structural repair and functional recovery in neurodegenerative models. Both paradigms circumvent traditional electrode drawbacks, eliminating mechanical trauma, corrosion risks, and charge diffusion, while leveraging wireless energy transfer. By enabling precise neuromodulation and enhancing neurogenesis, these innovations establish versatile frameworks for treating conditions ranging from chronic pain to traumatic brain injury, marking a shift toward biointegrated neural interfaces.

Another significant challenge in DBS is the noninvasive targeting of neurons within the brain parenchyma. Systemically administered piezoelectric nanoparticles offer a promising solution (Figure 11C).^[302] When exposed to high-intensity focused ultrasound, these nanoparticles generate direct current stimulation through the piezoelectric effect, triggering the release of nitric oxide (NO). NO temporarily disrupts the tight junctions of the blood–brain barrier, facilitating nanoparticle penetration into the brain parenchyma. In a Parkinson’s disease mouse model, this strategy significantly increased striatal dopamine levels (Figure 11D) and alleviated motor dysfunction by electrically stimulating dopaminergic neuron-like cells.^[302] Histological analysis confirmed minimal toxic accumulation of nanoparticles in the brain. This technology combines the energy conversion advantages of piezoelectric materials with the deep penetration capabilities of ultrasound, opening new avenues for minimally invasive treatments of neurodegenerative diseases such as Alzheimer’s.

For obesity and related metabolic disorders, noninvasive treatment methods are urgently needed. An oral self-powered voltage stimulator has been developed to achieve metabolic regulation by targeting the gastric vagus nerve (Figure 11E).^[303] Capsaicin (Cap) on the particle surface binds to TRPV1 receptors in the gastric mucosa, converting the mechanical energy of gastric peristalsis into electrical pulses via BTO piezoelectric materials. These pulses directly stimulate the afferent fibers of the vagus nerve. Animal experiments demonstrated that this stimulation suppresses appetite, enhances energy expenditure, and reduces fat production through the gut-brain axis, leading to significant weight loss in diet-induced obese mice. This technology operates without external power sources and avoids the gastrointestinal side effects associated with traditional drug therapies, offering a safe and reversible physical intervention strategy for obesity treatment.

Traditional neural probe implantation often results in tissue damage and chronic inflammation due to mechanical friction during insertion. Silicon-based ultrasonic neural probes (Figure 12A) address this issue through an innovative piezoelectric ceramic-driven mechanism: the probe tip incorporates a longitudinally resonant piezoelectric plate capable of generating micron-level, high-frequency vibrations at ultrasonic frequencies.^[304] This design leverages the tissue-hardening effect induced by high tip speed, which minimizes deformation and frictional resistance along the insertion path. Additionally, the silicon-based ultrasonic horn exhibits superior acoustic impedance matching with neural tissue compared to titanium alloys, enabling higher vibration amplitude transmission while maintaining mechanical integrity. Experimental validation in rat cortical implants (Figure 12B) demonstrates that the silicon-based ultrasonic neural probe significantly reduces tissue damage, suppresses inflammatory responses, and ensures long-term recording stability, offering a safer and more reliable tool for neuroscience research.^[304]

Peripheral nerve injury repair requires both physical guidance and biological activity regulation. The BTNPs/P(VDF-TrFE) oriented nanofiber hydrogel (Figure 12C) overcomes this challenge through a multimodal design.^[305] Electrospinning technology constructs aligned nanofibers, while BTNPs doping enhances the crystallinity of the β phase. Under ultrasonic thermal stimulation, the thermosensitive drug release layer, composed of pNIPAM hydrogel, undergoes volume contraction, triggering the controlled release of encapsulated nerve growth factor. This promotes neuronal growth (Figure 12D) and accelerates the reconstruction of damaged nerve structures and functions in a rat sciatic nerve defect model.^[305] These results highlight the dual functionality of BTNPs/P(VDF-TrFE) oriented nanofiber hydrogels in providing physical guidance and bioactive regulation, offering an effective therapeutic strategy for peripheral nerve injury repair.

Conventional deep brain stimulation is constrained by electrode size and energy diffusion limitations. The implantable piezoelectric ultrasonic stimulator (ImPULS) (Figure 12E) achieves a breakthrough through micro-nano fabrication.^[306] The device features an SU-8 substrate (0.8 μm in thickness), encapsulation and backing layers (0.5 and 15 μm in thickness, respectively), a piezoelectric KNN layer (1 μm in thickness, 100 μm in diameter), and Cr/Au (10/250 nm) and Pt (100 nm) as top and bottom electrodes, respectively, with Cr/Au serving as metal interconnects (10/250 nm in thickness). The fabrication process involves wet etching, patterning, and transfer printing of the piezoelectric film onto a polymer SU-8 substrate (Figure 12F).^[306] Experimental results demonstrate that ImPULS successfully stimulates mouse hippocampal neurons, activates c-Fos expression, and modulates dopamine release, showcasing its efficient neuromodulatory capabilities.

From ultrasound-driven probes to intelligent neural scaffolds and deep brain stimulators, piezoelectric technology has established a comprehensive “precision implantation-functional reconstruction-neural modulation” solution through multiscale innovation. These advancements not only significantly reduce the invasiveness of neural devices but also provide a transformative, integrated therapeutic platform for intractable conditions such as Parkinson’s disease and peripheral nerve injuries, enabled by energy autonomy and closed-loop feedback designs. With ongoing advancements in materials science and micro-nano fabrication, ultrasound-piezoelectric systems are poised to become the cornerstone of next-generation neural interface technologies.

4.6 Wound healing

PENG is revolutionizing wound care by enabling intelligent and dynamic solutions that integrate sensing and therapeutic functionalities. PENG facilitates real-time monitoring of wound healing stages, early detection of infection risks, and active promotion of tissue regeneration, offering a multimodal approach for managing chronic wounds, such as diabetic ulcers, and postoperative recovery.

The persistent biofilm in diabetic wounds is a major contributor to delayed healing. A sonocatalytic polysaccharide/NADH composite system has been developed to address this issue (Figure 13A).^[307] Under ultrasonic activation, this system generates reactive hydrogen species that rapidly penetrate and disrupt bacterial membrane potentials, inhibiting bacterial energy metabolism. Simultaneously, hydrogen (H₂) reacts with catalase within the biofilm, blocking the bacterial oxidative phosphorylation pathway (Figure 13B).^[307] Another innovative approach incorporates BTO nanoparticles to enable ultrasound-triggered piezoelectric catalytic therapy. Ultrasonic excitation of BTO generates a piezoelectric field, driving electron-hole separation and producing hydroxyl radicals (·OH) and superoxide anions (O₂⁻), thereby enhancing bactericidal efficiency. The composite hydrogel dressing, which embeds BTO nanoparticles within a gelatin/oxidized hyaluronic acid matrix (Figure 13C),^[308] exhibits strong adhesion, self-healing properties, and controlled reactive oxygen species (ROS) release, significantly accelerating skin wound repair (Figure 13D).^[308]

Electrical stimulation promotes epithelial regeneration by modulating cellular electrophysiological behavior, but traditional ES therapies are limited by the heterogeneous electrical responsiveness of cells. A breakthrough has been achieved with an electroresponsive hydrogel system loaded with a phosphatase and tensin homolog (PTEN) inhibitor. The synergistic effects of electrical stimulation and PTEN inhibition enhance vascular endothelial growth factor secretion and accelerate angiogenesis. Furthermore, a wearable DC pulse PENG converts the mechanical energy from rat movement into electrical signals (Figure 13E), enabling pulsed on-demand release of PTEN inhibitors from the hydrogel.^[309] This approach optimizes wound healing by improving cellular electrical responsiveness while minimizing the adverse effects associated with prolonged PTEN inhibition.

Conventional electronic dressings often require surgical removal, increasing infection risks. A biodegradable piezoelectric transient device, composed of γ-glycine/PVA piezoelectric film, addresses this limitation through optimized synthesis guided by density functional theory (Figure 13F).^[310] First-principles calculations and experimental validation reveal that γ-glycine crystals grow preferentially along the orientation, achieving a piezoelectric coefficient (d₃₃) of 10.4 pC/N, comparable to traditional PVDF. The film hydrolyzes in the slightly acidic wound environment within 14-days postimplantation, leaving no toxic residues and achieving a balance between effective treatment and safe degradation.

Chronic wounds often fail to heal due to the attenuation of bioelectric signals. To address this, ZnO nanoparticle-modified PVDF/sodium alginate (ZPFSA) scaffolds have been developed to reconstruct the electrical microenvironment through a dual piezoelectric effect (Figure 14A).^[311] The synergistic interaction between the β-phase of PVDF and ZnO nanoparticles enables the scaffold to mimic the natural wound potential in response to mechanical stress, thereby accelerating wound healing and minimizing scar formation. Notably, the ZPFSA 0.5 scaffold demonstrates exceptional biocompatibility, antibacterial properties, and a stable piezoelectric response, significantly enhancing the wound healing process within 2 weeks (Figure 14B).^[311] Complementarily, electrostimulation via flexible piezoelectric films offers another approach to restore bioelectric fields. Surface-functionalized BTO nanoparticles (BT@CDs@ArPFTU) were incorporated into electrospun P(VDF-TrFE) matrices, yielding films with elevated β-phase crystallinity and piezoelectric output. These P(VDF-TrFE)/BT@CDs@ArPFTU films were assembled into PENG, exhibiting robust electrical performance suitable for wireless electrostimulation.^[312]

Infected wounds necessitate simultaneous sterilization and tissue regeneration. A 3D-printed Janus piezoelectric patch has been designed to achieve dual-modal intervention via a cocktail therapy approach (Figure 14C).^[313] This patch comprises a polyethylene glycol diacrylate hydrogel layer enriched with tetragonal BTO and a methacrylate gelatin layer loaded with growth factors. Under ultrasound activation, the patch generates ROS for targeted sterilization while delivering growth factors to promote tissue regeneration. In vivo studies confirm the patch’s efficacy in mitigating infection and facilitating healing, underscoring its potential in programmable wound management strategies (Figure 14D).^[313] Addressing the specific challenge of tendon-to-bone healing, Janus asymmetric piezoelectric adhesives were developed. These consist of an adhesive hydrogel and a nonadhesive hydrogel assembled on a piezoelectric PLLA nanofiber mat, enabling minimally invasive application on irregular interfaces.^[314] Crucially, these adhesives exert superior anti-inflammatory effects. Mechanistic studies revealed that the piezoelectric stimulation activates the TRPV1 ion channel, promoting Ca²⁺ influx in macrophages and enhancing the cAMP signaling pathway.

Postoperative tumor recurrence and delayed wound healing are often concurrent challenges. A lactic acid-butylene glycol-sebacic acid-itaconic acid copolymer elastomer (PLBSIE) addresses these issues through a piezoelectric-chemodynamic synergistic design (Figure 14E).^[315] The ultrasound-activated PLBSIE platform demonstrates significant potential in eradicating tumor cells and accelerating wound healing via ROS generation and piezoelectric therapy, showcasing its multifunctionality in treating postoperative tumor-induced wounds (Figure 14F).^[315] This elastomer represents a promising solution for comprehensive postoperative care in osteosarcoma, highlighting its therapeutic versatility.

Complex wounds require both mechanical support and infection control. Silk fibroin/polyethylene glycol diacrylate/Ag@BT (SPAB) hydrogels, fabricated using digital light processing 3D printing, offer customizable structures to meet these needs (Figure 14G).^[316] Under ultrasound stimulation, these hydrogels exhibit remarkable antibacterial efficacy against Escherichia coli and Staphylococcus aureus, achieving antibacterial rates of 99.23% and 99.96%, respectively. The ultrasound-induced piezoelectric catalytic effect enhances ROS production, further promoting wound healing and combating bacterial infections.

A novel rotary jet-spun all-organic piezoelectret textile overcomes the functionality-comfort trade-off in wearables. Electrical poling significantly enhances its piezoelectric output, attributed to trapped polarized charges. The textile demonstrates high pressure sensitivity, effective waterproofness, and excellent breathability, ensuring user comfort. Beyond monitoring physiological signals like pulse and respiration, it functions as a deep learning-assisted pressure-mapping sensor array with high accuracy. Crucially, its piezoelectricity induces electrical stimulation that accelerates cell proliferation and migration, highlighting its dual potential for advanced biosensing and smart wound dressings, offering a scalable biomedical solution.

PENG have established a new paradigm for intelligent wound healing through multidisciplinary innovation. These advancements address critical challenges in chronic wound management, such as biofilm resistance, slow cell regeneration, secondary surgical trauma, scar formation, and postoperative recurrence. By integrating energy autonomy and closed-loop feedback designs, PENG-based systems provide a scalable platform for personalized medicine, paving the way for next-generation wound care solutions.

5.1 Power generation efficiency and energy storage challenges

The energy conversion efficiency of PENG is fundamentally limited by several material, structural, and electrical factors. The choice of piezoelectric materials remains a primary constraint, as many exhibit suboptimal energy harvesting performance compared to alternative technologies.^[317] Low power output—typically in the microwatt to milliwatt range—further restricts their applicability in high-energy-demand scenarios, due to limited charge generation per deformation cycle and high internal impedance.^[318,319] Structural inefficiencies, including inadequate mechanical coupling, nonoptimized architectures, and long-term material fatigue, can also degrade performance.^[320] In addition, charge loss through recombination and leakage, compounded by internal capacitance and resistance, reduces effective output.^[321] Impedance mismatching between the PENG and external circuits leads to further power loss, highlighting the need for optimized load-matching strategies.^[322] PENG To overcome energy conversion limitations in PENG, we transition from passive optimization to active intelligent systems. ML—particularly graph neural networks—accelerates the discovery of application-tailored piezoelectric materials. Concurrently, quantum-confined architectures incorporating strain-engineered quantum wells in piezoelectric semiconductors radically enhance charge separation efficiency by directly converting nanoscale lattice vibrations into usable electrons.

Efficient energy storage is paramount to overcoming the inherent challenges of PENG, which produce intermittent and low-power output. A key issue is the low energy density of PENG, as the energy harvested per mechanical cycle is minimal.^[323] This necessitates the use of advanced storage solutions, such as supercapacitors or microbatteries, capable of efficiently storing small, irregular energy bursts.^[323] Additionally, the intermittent and unpredictable nature of PENG output, driven by mechanical stimulation, complicates direct power utilization. Energy storage systems must not only capture these fluctuating inputs but also stabilize them to deliver a consistent power supply. Another challenge lies in energy transfer inefficiencies, where losses during rectification, impedance matching, and energy conversion reduce overall system efficiency.^[320] Scalability and integration further present significant hurdles, particularly for applications requiring compact, lightweight, and flexible designs, such as wearable or implantable devices.^[320] Developing energy storage solutions that balance high capacity, flexibility, and compatibility with PENG is complex, as it involves navigating trade-offs between size, weight, and functionality. Addressing these challenges is essential for advancing PENG-based energy harvesting systems, enabling their practical application in powering low-energy devices such as sensors, wearables, and biomedical implants. Addressing PENG energy storage demands a shift from discrete devices to biointegrated systems. We propose intelligent energy ecosystems where biocoupled supercapacitors, using DNA-origami electrodes that mimic mitochondrial morphology, achieve ultrahigh Coulombic efficiency; meanwhile, self-regulating near-zero-power wake-up controllers enable event-driven prioritization of critical biomedical data transmission during energy-scarce conditions. This integrated approach fundamentally transforms intermittent outputs into reliable power for sustained medical device operation, ensuring clinical-grade reliability.

5.2 Biocompatibility and long-term stability in the human body

PENG holds significant promises such as self-powered biomedical implants, wearable health monitors, and drug delivery systems due to their ability to convert mechanical energy into electrical energy. However, their successful integration into the human body hinges on 2 critical factors: biocompatibility and long-term stability. Ensuring that PENG do not elicit adverse biological responses while maintaining functional efficiency over extended periods remains a major challenge.

5.3 Mechanical durability and flexibility for biomedical monitoring

PENG faces substantial challenges in achieving mechanical durability and flexibility for biomedical use, as they must withstand repeated mechanical stress while conforming to dynamic biological surfaces. Many conventional materials are brittle and prone to fatigue, leading to functional degradation under cyclic loading. In contrast, flexible alternatives often suffer from reduced piezoelectric performance and long-term instability. Adhesion between active materials and soft substrates remains problematic, as delamination under strain can diminish energy output. Material selection is further constrained by biocompatibility requirements, limiting the use of high-efficiency but toxic components. Environmental factors, including moisture, temperature variations, and biological fluids, pose additional risks to device stability without effective encapsulation. Moreover, seamless integration with sensors and electronics is complicated by strain-induced property changes and interfacial resistance. Overcoming these issues requires advances in composite material design, resilient microstructures, and biocompatible architectures to ensure long-term, high-performance operation in wearable or implantable settings.

Biological intelligence inspires revolutionary solutions: Mussel foot-inspired polymers achieve self-healing through reversible sacrificial bonds, dynamically repairing microdamage during stress. Pericarp-mimetic barriers provide seamless environmental defense while maintaining exceptional flexural compliance. This harmonious fusion of nature’s designs transforms rigid devices into adaptive biomechanical interfaces, ensuring enduring functionality within living systems.

6.1 Conclusion

PENG have emerged as a transformative technology in biomedical diagnostics, seamlessly integrating energy harvesting and precision sensing to redefine the monitoring and interpretation of physiological signals. Recent advancements underscore their revolutionary potential in healthcare: in cardiovascular monitoring, wearable PENG patches enable real-time tracking of HR, blood pressure, and vascular health; in respiratory diagnostics, flexible PENG-based sensors provide critical metrics such as respiratory rate, tidal volume, and obstruction status, aiding in the diagnosis of lung diseases; in neuromuscular interfaces, PENG decode muscle contractions and gait dynamics, enhancing the quality of life for patients with specific health conditions; and in metabolic and neural sensing, implantable PENG devices monitor blood glucose dynamics and brain activity, while smart wound dressings leverage self-generated electric fields to combat infections and accelerate healing. These innovations highlight the immense potential of PENG in advancing personalized medicine and enabling real-time health monitoring.

PENG demonstrates significant near-term potential for clinical translation, particularly in cardiovascular monitoring, respiratory sensing, and wound healing, driven by compelling preclinical results and simpler integration pathways. In cardiovascular applications, implantable PENG like ultrathin PVDF/HHE sensors have successfully tracked real-time hemodynamics and micropressure changes in arterial walls within living pig models,^[273] while wearable versions, such as piezoelectric sensors embedded in watch straps, have already achieved clinical validation with accuracy comparable to standard blood pressure monitors.^[278] For respiratory monitoring, fully integrated wearable solutions exist, including smart masks with 3D-printed cellulose nanocrystal sensors capable of autonomously distinguishing breathing patterns^[285] and PLLA-based airflow transducers that have quantified metabolic rates in human trials.^[286] Wound healing represents another highly promising near-term application, where PENG-based dressings incorporating materials like ZnO-PVDF/sodium alginate scaffolds showed 98.74% wound closure within 14 days in vivo studies, simultaneously offering antibacterial benefits and biocompatibility.^[311] While neural interfaces and metabolic tracking hold future promises, challenges like chronic biocompatibility, power stability, and complex regulatory hurdles currently delay their clinical entry. In contrast, cardiovascular, respiratory, and wound-healing PENG leverage their relative simplicity of integration, lower power requirements, and robust preclinical performance data, positioning them clearly at the forefront for imminent clinical adoption.

However, the path to clinical translation is fraught with challenges. Limitations in power density restrict their use in energy-intensive applications, and the long-term stability of biocompatible materials in corrosive physiological environments remains uncertain. Mechanical fatigue under cyclic stress and the integration of sustainable energy storage systems also demand urgent attention. Addressing these issues will require interdisciplinary collaboration, uniting expertise in materials engineering, biomechanics, and data science to overcome existing barriers and unlock the full potential of PENG in biomedical applications (Figure 15).

6.2 Prospects