The realm of implantable bioelectronics represents a frontier in medical science, merging technology, biology, and medicine to innovate treatments that enhance, restore, or monitor physiological functions. This field has yielded devices like cochlear implants, cardiac pacemakers, deep brain stimulators, and vagus nerve stimulators, each designed to address a specific health condition, ranging from sensorineural hearing loss to chronic pain, neurological disorders, and heart rhythm irregularities. Such devices underscore the potential of bioelectronics to significantly improve patient outcomes and quality of life. Recent technological breakthroughs in materials science, nanotechnology, and microfabrication have enabled the development of more sophisticated, smaller, and biocompatible bioelectronic devices. However, the field also encounters challenges, particularly in extending the capabilities of devices such as retinal prostheses, which aim to restore vision but currently offer limited visual acuity. Research in implantable bioelectronics is highly timely, driven by an aging global population with a growing prevalence of chronic diseases that could benefit from these technologies. The convergence of societal health needs, advancing technological capabilities, and a supportive ecosystem for innovation marks this era as pivotal for bioelectronic research.

The field of implantable bioelectronics is rapidly evolving and sits at the confluence of technology, medicine, and biology. This interdisciplinary field focuses on developing and integrating electronic devices that can be implanted in the human body to treat, diagnose, or assist in the recovery of various medical conditions. The technological challenges and exploration of new applications in this field are vast and diverse, reflecting the complexity and potential of integrating electronics with biological systems.

Several bioelectronic technologies have already achieved significant success, demonstrating a profound impact on healthcare and patient outcomes. These technologies range from devices that restore lost functions to those that manage chronic conditions. Notable examples include cochlear implants, cardiac pacemakers, deep brain stimulators (DBSs), spinal cord stimulators, and vagus nerve stimulators.

Cochlear implants are among the most successful bioelectronic devices, transforming the lives of individuals with severe to profound sensorineural hearing loss. The success of cochlear implants has been a significant milestone in bioelectronics, proving that direct electrical stimulation of nerves can restore a sense. Pacemakers and implantable cardioverter-defibrillators (ICDs) are life-saving devices that regulate heart rhythm. Deep brain stimulation (DBS) devices are used to treat a variety of neurological conditions, most notably Parkinson's disease, essential tremor, and dystonia. The success of DBS has paved the way for exploring electrical stimulation therapies for other neurological and psychiatric disorders. DBS has also seen a recent translational focus on its use for brain–computer interfaces (BCIs). Both Synchron1 and Neuralink2 are currently conducting first-in-human trials of permanently implantable BCIs to enable mental control of a computer by patients with paralysis. Vagus Nerve Stimulators (VNSs) are used primarily to treat epilepsy and depression. Finally, Sacral Nerve Stimulator (SNS) devices are implanted to treat bladder control problems and fecal incontinence. These examples illustrate the breadth and impact of implantable bioelectronic technologies. As research progresses, it is expected that new devices and applications will emerge, further expanding the potential of bioelectronics to address unmet medical needs. Notable examples of such innovation are smart cardiac patches and smart scaffolds.3 Contemporary research in this field addresses new applications to meet the evolving needs of the medical field. Foremost, as the global population ages, there is an increasing prevalence of chronic diseases and conditions that could benefit from implantable bioelectronics, such as neurodegenerative diseases, vision loss, and mobility issues. Implantable devices offer potential treatments that could improve the quality of life and independence for older adults.

Several recent processes are shaping research in the field. Foremost, many conditions that implantable bioelectronics aim to treat or manage are not adequately addressed by current medical treatments. For example, pharmacological treatments for chronic pain or neurological disorders often come with significant side effects. Implantable devices offer an alternative that can be more effective and have fewer side effects. Although the field of implantable bioelectronics dates back centuries, it recently experienced an increase in funding and public interest. Both public and private sectors are recognizing the potential impact of implantable bioelectronics on healthcare. Increased funding and investment are fueling research and development, accelerating the pace of discovery and application. The rise of digital health and wearable technology has laid the groundwork for the acceptance and integration of more advanced technologies like implantable bioelectronics. Wearable technology may also contribute to enhancing implantable device performances by, for example, facilitating wireless data and energy transfer.4 There is a growing interest in leveraging technology to monitor and improve health, making it a ripe time for introducing new bioelectronic devices. Finally, regulatory bodies are beginning to recognize the importance of supporting and fast-tracking the development of medical devices that can significantly impact patient care. This support is critical for bringing new technologies from the lab to the clinic.

In summary, the convergence of societal health needs, technological capability, and a supportive ecosystem makes the research in implantable bioelectronics not only timely but also essential. It represents a promising frontier in medicine, with the potential to transform the way we treat and manage a wide range of health conditions.

Despite the great progress achieved in some domains, several technological challenges persist and research in implantable bioelectronics constantly seeks new solutions to achieve better device stability5 and performances and to identify new frontiers. Implantable bioelectronic devices constantly evolve benefitting from ongoing technological advancements. Recent breakthroughs in materials science, nanotechnology, microfabrication, and tissue engineering have made it possible to design and manufacture devices that were not feasible a decade ago.6 These advancements enable the creation of smaller, more efficient, and biocompatible devices.

In some domains, bioelectronic devices have yet to reach a high level of maturity demanding further technological innovation. A prime example is the field of retinal prostheses.7 Also known as “bionic eyes,” retinal prostheses aim to restore vision to individuals blinded by retinal diseases such as retinitis pigmentosa and age-related macular degeneration. These devices convert images captured by a camera into electrical signals, which are then transmitted to the retina to create visual perceptions. While the vision restored by current retinal prostheses is limited, they represent a significant advancement in efforts to restore sight.

Altogether, established [Fig. 1(a)] and emerging [Fig. 1(b)] implantable bioelectronic devices are witnessing advancements facilitated by new technologies, including flexible and soft electronics,3 sensor technology, nanomaterials, simulations, fabrication, and refined signal analysis approaches [Fig. 1(c)]. These innovations open avenues for enhancing existing devices and enabling the development of novel applications, such as cardiac patches for continuous monitoring of cardiac activity. Additionally, emerging fields [Fig. 1(d)] such as digital health and wearable technologies4 present fresh opportunities for the utilization of implantable bioelectronic devices in novel ways in the future.

FIG. 1.

Established (a) and emerging (b) implantable bioelectronic devices. New technologies such as flexible and soft electronics,3 sensor technology, nanomaterials, simulations, fabrication, and refined signal analysis approach (c) open new opportunities in improving existing devices or facilitating the formation of new applications such as cardiac patches for ongoing monitoring of cardiac activity. Emerging fields (d) such as digital health and wearable technologies4 offer new opportunities in the utilization of implantable bioelectronic devices.

FIG. 1.

Established (a) and emerging (b) implantable bioelectronic devices. New technologies such as flexible and soft electronics,3 sensor technology, nanomaterials, simulations, fabrication, and refined signal analysis approach (c) open new opportunities in improving existing devices or facilitating the formation of new applications such as cardiac patches for ongoing monitoring of cardiac activity. Emerging fields (d) such as digital health and wearable technologies4 offer new opportunities in the utilization of implantable bioelectronic devices.

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This collection addresses several timely topics in bioelectronics. In the realm of technology, the collection includes reports on new electrode materials, modeling electric field distribution for direct current stimulation, new sensors, optrodes technology, packaging challenges of soft probes, and novel fabrication technologies. The collection also includes examples of new exploration into specific bioelectronics applications: Artificial Retina, spinal cord stimulation, and regenerative therapy after spinal cord injury.

A topic of particular interest in bioelectronics is improved electrode performance. Developing electrodes that are biocompatible, durable, and efficient in transmitting electrical signals to neural tissues is crucial. Materials such as conductive polymers, carbon nanotubes, and graphene are being explored for their potential to improve electrode performance. The study reported by Dijk et al. investigates the use of PEDOT:PSS-coated platinum (Pt-PEDOT:PSS) microelectrodes for safe and long-term neural stimulation compared to bare platinum (Pt) electrodes. The PEDOT:PSS coating prevents Pt corrosion and degradation during stimulation. This study highlights the protective properties of PEDOT:PSS, offering a promising approach to extend electrode lifetime and minimize cell damage for safe and long-term neural stimulation.8 

Understanding how electrical fields are distributed within biological tissues during stimulation is another essential element, needed for optimizing device efficacy. Advanced computational models are used to predict field distribution and inform electrode design and placement, enhancing the safety and effectiveness of treatments like DBS. Recent advancements in electric field-stimulated axonal regrowth offer promise for neuronal regeneration. However, understanding the exogenous electric field distribution in injured tissue, influenced by electrode geometry and placement, remains a challenge. The study in Ref. 9 focuses on spinal cord injury (SCI), resulting from trauma or disease. This study presents a finite element model of spinal cord treatment to investigate these factors. Results indicate that electrode shape minimally affects the induced electric field, while electrode placement significantly influences field distribution. The magnitude of the field depends on applied current and spinal cord morphology. Injury modality also impacts field distribution, suggesting a need for tailored treatment parameters. The research offers insights for optimizing electrode design in direct current electric field stimulation for axonal regeneration, aiming to guide future clinical applications.9 

Another innovative approach presented in the collection is the optrodes. Combining optical and electrical stimulation, optrodes allow for more precise control of bioelectronic devices. This technology is particularly promising for applications requiring the activation or inhibition of specific neural pathways with high spatial and temporal resolution.10 In Ref. 10, Almasri and co-authors review optrode applications in electrophysiology, encompassing both established and emerging sensing and stimulation technologies. They delve into the architectures and designs utilized for soft and flexible optrode arrays and devices. They then delineate the common components of flexible optrode arrays, exploring fabrication methods and material classifications for each component and correlating them with various applications and targeted tissues. In Ref. 10, they also scrutinize design considerations, major challenges, and technical requisites necessary for the clinical translation and commercial production of soft and flexible optrode arrays for both acute and chronic applications. Finally, they outline future trajectories, addressing existing gaps in terms of novel materials and fabrication avenues for emerging optical technologies.

Ensuring the long-term stability and biocompatibility of implantable devices is a significant challenge. Packaging must protect the device from the body's environment while being flexible enough to move with surrounding tissues, reducing the risk of damage or rejection. In Ref. 11, the authors present a novel solution for interconnecting soft-to-flexible bioelectronic interfaces, which involves utilizing a flexible printed circuit board interfaced with soft transducing systems. Arrays of protruding “fingers” bearing individual electrical terminals are laser-machined onto a standard flexible printed circuit board to create a comb-like structure. The team investigated the electrical and electromechanical properties of this interconnection method and showcased its versatility and scalability through various customized designs. In a preliminary in vivo study, they validated the stability and compatibility of the technology by implanting a subdural electrocorticography system on the auditory cortex of a minipig for 6 months. The proposed new approach's potential is in applications in soft robotics, wearable technology, and implantable bioelectronics.

The development of new fabrication methods is also essential for creating smaller, more complex devices that can interface with biological tissues at the cellular level. Techniques such as 3D printing and microfabrication are being explored to produce next-generation bioelectronics.12 Kang and co-workers demonstrated the functionality of large-area solution-processed indium-gallium-zinc oxide (IGZO) based electrolyte-gated thin film transistor (EGTFT) arrays operating at low voltages (below 0.5 V). These devices exhibited long-term stability and resilience in aqueous electrolytes under physiological conditions. Additionally, experimental validation confirmed the biocompatibility of IGZO surfaces with various mammalian cells, assessing parameters. Notably, IGZO-EGTFT devices in direct contact with live cells showed prolonged stable operation and exhibited changes in channel current and threshold voltages depending on cell attachment. These findings suggest the feasibility of solution-processed metal oxide-based interfaces with cells, paving the way for durable implantable or on-chip devices capable of real-time monitoring of cellular behaviors and biochemical signals.

Restoring vision to individuals with retinal diseases involves creating devices that can translate visual information into electrical signals the brain can interpret. This requires sophisticated interfaces that can integrate with the retinal tissue. In Ref. 13, the authors report on a bulk heterostructure semiconductor blend with a wide spectral response range, as a means to stimulate electrical activity in the retina. This combination induces clear spiking activity in a developing blind-chick embryonic retina when configured in a subretinal arrangement and exposed to white light. Notably, the response is predominantly triggered by the blue-green spectral range, rather than the red-near-infrared range, aligning with the attributes of the polymer semiconductor layer utilized in this study. This study further supports the potential of novel materials in advancing bioelectronic systems.

Used for pain management and to restore function after injury, spinal cord stimulation involves delivering electrical pulses to the spinal cord. Research focuses on improving the precision and efficacy of stimulation to enhance outcomes. In particular, bioelectronic devices are being explored as a mean to promote nerve growth and recovery after spinal cord injuries. This includes devices that can deliver electrical or chemical stimuli to encourage nerve regeneration. In Ref. 14, the authors explore diverse engineering strategies for generating regenerative electric fields (EFs) through direct current electrical stimulation and very low-frequency electrical stimulation. They highlight the significance of the electrode–tissue interface in selecting appropriate electrode materials and stimulator circuitry. Additionally, they discuss methodologies for accurately estimating and controlling the generated field, needed for ensuring comparability across studies. Furthermore, they evaluate different approaches employed to assess functional recovery post-injury and treatment. By reviewing studies in the field of electrical stimulation therapy, they aim to provide insights to help inform decisions on optimal stimulation strategies and recovery assessment methods for future research endeavors.

Implantable devices that can monitor and regulate bladder function are being developed to treat conditions like incontinence and overactive bladder. These devices work by stimulating nerves or muscles involved in bladder control, offering an alternative to pharmaceutical treatments.15 Giannotti and co-workers report on the application of a Random Forest classifier, to decode three bladder-filling states: empty, full, and during micturition. Across all five tested animals, the decoding algorithm consistently achieved a mean balanced accuracy exceeding 86.67%, for all three classes. The reported method may offer an advancement toward establishing an adaptive real-time closed-loop stimulation protocol for pudendal nerve modulation.

The field of implantable bioelectronics holds the promise of revolutionizing medical treatment for a wide range of conditions. By overcoming the current technological challenges and exploring new applications, researchers are paving the way for a future where bioelectronic devices can seamlessly integrate with the human body to restore, enhance, or monitor physiological functions as detailed in Ref. 16. The authors explore the foundational engineering principles underlying the gap between implantable sensor research and clinical adoption. Emphasizing the importance of carefully considering clinical requirements and engineering challenges, they underscore the need for future research to address issues such as long-term performance, biocompatibility, and power sources. Furthermore, they highlight the transformative potential of implantable sensors across various healthcare disciplines. While implantable sensors hold significant promise in medical technology, the substantial gap between research and clinical adoption persists, with major obstacles yet to be overcome before they can be widely integrated into medical practice.

The field of implantable bioelectronics, situated at the intersection of technology, medicine, and biology, is rapidly evolving, focusing on developing devices that can be implanted in the human body to treat, diagnose, or assist recovery from various medical conditions. This interdisciplinary area faces technological challenges but has seen significant successes, which illustrate the impact of bioelectronics in healthcare, offering potential improvements in life quality and independence, particularly for the aging global population. Advances in materials science, nanotechnology, artificial intelligence, and microfabrication are driving the creation of smaller, more efficient, and biocompatible devices. Research is timely, fueled by societal health needs, technological capabilities, and a supportive ecosystem, promising to transform medical treatments across a wide range of conditions.

We thank the authors who contributed the papers to this collection, the journal editors for valuable comments, and the staff who assisted in preparing this collection.

The authors have no conflicts to disclose.

Ethics approval is not required.

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