Stretchable Functional Nanocomposites for Soft Implantable Bioelectronics.

Material advances in soft bioelectronics, particularly those based on stretchable nanocomposites─functional nanomaterials embedded in viscoelastic polymers with irreversible or reversible bonds─have driven significant progress in translational medical device research. The unique mechanical properties inherent in the stretchable nanocomposites enable stiffness matching between tissue and device, as well as its spontaneous mechanical adaptation to in vivo environments, minimizing undesired mechanical stress and inflammation responses. Furthermore, these properties allow percolative networks of conducting fillers in the nanocomposites to be sustained even under repetitive tensile/compressive stresses, leading to stable tissue-device interfacing. Here, we present an in-depth review of materials strategies, fabrication/integration techniques, device designs, applications, and translational opportunities of nanocomposite-based soft bioelectronics, which feature intrinsic stretchability, self-healability, tissue adhesion, and/or syringe injectability. Among many, applications to brain, heart, and peripheral nerves are predominantly discussed, and translational studies in certain domains such as neuromuscular and cardiovascular engineering are particularly highlighted.

Material Design and Fabrication Strategies for Stretchable Metallic Nanocomposites.

Stretchable conductive nanocomposites fabricated by integrating metallic nanomaterials with elastomers have become a vital component of human-friendly electronics, such as wearable and implantable devices, due to their unconventional electrical and mechanical characteristics. Understanding the detailed material design and fabrication strategies to improve the conductivity and stretchability of the nanocomposites is therefore important. This Review discusses the recent technological advances toward high performance stretchable metallic nanocomposites. First, the effect of the filler material design on the conductivity is briefly discussed, followed by various nanocomposite fabrication techniques to achieve high conductivity. Methods for maintaining the initial conductivity over a long period of time are also summarized. Then, strategies on controlled percolation of nanomaterials are highlighted, followed by a discussion regarding the effects of the morphology of the nanocomposite and postfabricated 3D structures on achieving high stretchability. Finally, representative examples of applications of such nanocomposites in biointegrated electronics are provided. A brief outlook concludes this Review.

Electronic sensor and actuator webs for large-area complex geometry cardiac mapping and therapy.

Curved surfaces, complex geometries, and time-dynamic deformations of the heart create challenges in establishing intimate, nonconstraining interfaces between cardiac structures and medical devices or surgical tools, particularly over large areas. We constructed large area designs for diagnostic and therapeutic stretchable sensor and actuator webs that conformally wrap the epicardium, establishing robust contact without sutures, mechanical fixtures, tapes, or surgical adhesives. These multifunctional web devices exploit open, mesh layouts and mount on thin, bio-resorbable sheets of silk to facilitate handling in a way that yields, after dissolution, exceptionally low mechanical moduli and thicknesses. In vivo studies in rabbit and pig animal models demonstrate the effectiveness of these device webs for measuring and spatially mapping temperature, electrophysiological signals, strain, and physical contact in sheet and balloon-based systems that also have the potential to deliver energy to perform localized tissue ablation.

Next-Generation Cardiac Interfacing Technologies Using Nanomaterial-Based Soft Bioelectronics.

Cardiac interfacing devices are essential components for the management of cardiovascular diseases, particularly in terms of electrophysiological monitoring and implementation of therapies. However, conventional cardiac devices are typically composed of rigid and bulky materials and thus pose significant challenges for effective long-term interfacing with the curvilinear surface of a dynamically beating heart. In this regard, the recent development of intrinsically soft bioelectronic devices using nanocomposites, which are fabricated by blending conductive nanofillers in polymeric and elastomeric matrices, has shown great promise. The intrinsically soft bioelectronics not only endure the dynamic beating motion of the heart and maintain stable performance but also enable conformal, reliable, and large-area interfacing with the target cardiac tissue, allowing for high-quality electrophysiological mapping, feedback electrical stimulations, and even mechanical assistance. Here, we explore next-generation cardiac interfacing strategies based on soft bioelectronic devices that utilize elastic conductive nanocomposites. We first discuss the conventional cardiac devices used to manage cardiovascular diseases and explain their undesired limitations. Then, we introduce intrinsically soft polymeric materials and mechanical restraint devices utilizing soft polymeric materials. After the discussion of the fabrication and functionalization of conductive nanomaterials, the introduction of intrinsically soft bioelectronics using nanocomposites and their application to cardiac monitoring and feedback therapy follow. Finally, comments on the future prospects of soft bioelectronics for cardiac interfacing technologies are discussed.

Materials and designs for wirelessly powered implantable light-emitting systems.

Strategies are presented to achieve bendable and stretchable systems of microscale inorganic light-emitting diodes with wireless powering schemes, suitable for use in implantable devices. The results include materials strategies, together with studies of the mechanical, electronic, thermal and radio frequency behaviors both in vitro and in in-vivo animal experiments.

Stretchable, transparent graphene interconnects for arrays of microscale inorganic light emitting diodes on rubber substrates.

This paper describes the fabrication and design principles for using transparent graphene interconnects in stretchable arrays of microscale inorganic light emitting diodes (LEDs) on rubber substrates. We demonstrate several appealing properties of graphene for this purpose, including its ability to spontaneously conform to significant surface topography, in a manner that yields effective contacts even to deep, recessed device regions. Mechanics modeling reveals the fundamental aspects of this process, as well as the use of the same layers of graphene for interconnects designed to accommodate strains of 100% or more, in a completely reversible fashion. These attributes are compatible with conventional thin film processing and can yield high-performance devices in transparent layouts. Graphene interconnects possess attractive features for both existing and emerging applications of LEDs in information display, biomedical systems, and other environments.

Stretchable colour-sensitive quantum dot nanocomposites for shape-tunable multiplexed phototransistor arrays.

High-performance photodetecting materials with intrinsic stretchability and colour sensitivity are key requirements for the development of shape-tunable phototransistor arrays. Another challenge is the proper compensation of optical aberrations and noises generated by mechanical deformation and fatigue accumulation in a shape-tunable phototransistor array. Here we report rational material design and device fabrication strategies for an intrinsically stretchable, multispectral and multiplexed 5 × 5 × 3 phototransistor array. Specifically, a unique spatial distribution of size-tuned quantum dots, blended in a semiconducting polymer within an elastomeric matrix, was formed owing to surface energy mismatch, leading to highly efficient charge transfer. Such intrinsically stretchable quantum-dot-based semiconducting nanocomposites enable the shape-tunable and colour-sensitive capabilities of the phototransistor array. We use a deep neural network algorithm for compensating optical aberrations and noises, which aids the precise detection of specific colour patterns (for example, red, green and blue patterns) both under its flat state and hemispherically curved state (radius of curvature of 18.4 mm).

Dissolvable films of silk fibroin for ultrathin conformal bio-integrated electronics.

Electronics that are capable of intimate, non-invasive integration with the soft, curvilinear surfaces of biological tissues offer important opportunities for diagnosing and treating disease and for improving brain/machine interfaces. This article describes a material strategy for a type of bio-interfaced system that relies on ultrathin electronics supported by bioresorbable substrates of silk fibroin. Mounting such devices on tissue and then allowing the silk to dissolve and resorb initiates a spontaneous, conformal wrapping process driven by capillary forces at the biotic/abiotic interface. Specialized mesh designs and ultrathin forms for the electronics ensure minimal stresses on the tissue and highly conformal coverage, even for complex curvilinear surfaces, as confirmed by experimental and theoretical studies. In vivo, neural mapping experiments on feline animal models illustrate one mode of use for this class of technology. These concepts provide new capabilities for implantable and surgical devices.

Functionalized Elastomers for Intrinsically Soft and Biointegrated Electronics.

Elastomers are suitable materials for constructing a conformal interface with soft and curvilinear biological tissue due to their intrinsically deformable mechanical properties. Intrinsically soft electronic devices whose mechanical properties are comparable to human tissue can be fabricated using suitably functionalized elastomers. This article reviews recent progress in functionalized elastomers and their application to intrinsically soft and biointegrated electronics. Elastomers can be functionalized by adding appropriate fillers, either nanoscale materials or polymers. Conducting or semiconducting elastomers synthesized and/or processed with these materials can be applied to the fabrication of soft biointegrated electronic devices. For facile integration of soft electronics with the human body, additional functionalization strategies can be employed to improve adhesive or autonomous healing properties. Recently, device components for intrinsically soft and biointegrated electronics, including sensors, stimulators, power supply devices, displays, and transistors, have been developed. Herein, representative examples of these fully elastomeric device components are discussed. Finally, the remaining challenges and future outlooks for the field are presented.

Durable and Fatigue-Resistant Soft Peripheral Neuroprosthetics for In Vivo Bidirectional Signaling.

Soft neuroprosthetics that monitor signals from sensory neurons and deliver motor information can potentially replace damaged nerves. However, achieving long-term stability of devices interfacing peripheral nerves is challenging, since dynamic mechanical deformations in peripheral nerves cause material degradation in devices. Here, a durable and fatigue-resistant soft neuroprosthetic device is reported for bidirectional signaling on peripheral nerves. The neuroprosthetic device is made of a nanocomposite of gold nanoshell (AuNS)-coated silver (Ag) flakes dispersed in a tough, stretchable, and self-healing polymer (SHP). The dynamic self-healing property of the nanocomposite allows the percolation network of AuNS-coated flakes to rebuild after degradation. Therefore, its degraded electrical and mechanical performance by repetitive, irregular, and intense deformations at the device-nerve interface can be spontaneously self-recovered. When the device is implanted on a rat sciatic nerve, stable bidirectional signaling is obtained for over 5 weeks. Neural signals collected from a live walking rat using these neuroprosthetics are analyzed by a deep neural network to predict the joint position precisely. This result demonstrates that durable soft neuroprosthetics can facilitate collection and analysis of large-sized in vivo data for solving challenges in neurological disorders.

Materials engineering, processing, and device application of hydrogel nanocomposites.

Hydrogels are widely implemented as key materials in various biomedical applications owing to their soft, flexible, hydrophilic, and quasi-solid nature. Recently, however, new material properties over those of bare hydrogels have been sought for novel applications. Accordingly, hydrogel nanocomposites, i.e., hydrogels converged with nanomaterials, have been proposed for the functional transformation of conventional hydrogels. The incorporation of suitable nanomaterials into the hydrogel matrix allows the hydrogel nanocomposite to exhibit multi-functionality in addition to the biocompatible feature of the original hydrogel. Therefore, various hydrogel composites with nanomaterials, including nanoparticles, nanowires, and nanosheets, have been developed for diverse purposes, such as catalysis, environmental purification, bio-imaging, sensing, and controlled drug delivery. Furthermore, novel technologies for the patterning of such hydrogel nanocomposites into desired shapes have been developed. The combination of such material engineering and processing technologies has enabled the hydrogel nanocomposite to become a key soft component of electronic, electrochemical, and biomedical devices. We herein review the recent research trend in the field of hydrogel nanocomposites, particularly focusing on materials engineering, processing, and device applications. Furthermore, the conclusions are presented with the scope of future research outlook, which also includes the current technical limitations.

Facilitated Transdermal Drug Delivery Using Nanocarriers-Embedded Electroconductive Hydrogel Coupled with Reverse Electrodialysis-Driven Iontophoresis.

We herein developed an iontophoretic transdermal drug delivery system for the effective delivery of electrically mobile drug nanocarriers (DNs). Our system consists of a portable and disposable reverse electrodialysis (RED) battery that generates electric power for iontophoresis through the ionic exchange. In addition, in order to provide a drug reservoir to the RED-driven iontophoretic system, an electroconductive hydrogel composed of polypyrrole-incorporated poly(vinyl alcohol) (PYP) was used. The PYP hydrogel facilitated electron transfer from the RED battery and accelerated the mobility of electrically mobile DNs released from the PYP hydrogel. In this study, we showed that fluconazole- or rosiglitazone-loaded DNs could be functionalized with charge-inducing agents, and DNs with charge modification resulted in facilitated transdermal transport via repulsive RED-driven iontophoresis. In addition, topical application and RED-driven iontophoresis of rosiglitazone-loaded DNs resulted in an effective antiobese condition displaying decreased bodyweight, reduced glucose level, and increased conversion of white adipose tissues to brown adipose tissues in vivo. Consequently, we highlight that this transdermal drug delivery platform would be extensively utilized for delivering diverse therapeutic agents in a noninvasive way.

Bioresorbable Electronic Implants: History, Materials, Fabrication, Devices, and Clinical Applications.

Medical implants, either passive implants for structural support or implantable devices with active electronics, have been widely used for the diagnosis and treatment of various diseases and clinical issues. These implants offer various functions, including mechanical support of biological structures in orthopedic and dental applications, continuous electrophysiological monitoring and feedback of electrical stimulation in neuronal and cardiac applications, and controlled drug delivery while maintaining arterial structure in drug-eluting stents. Although these implants exhibit long-term biocompatibility, surgery for their retrieval is often required, which imposes physical, biological, and economical burdens on the patients. Therefore, as an alternative to such secondary surgeries, bioresorbable implants that disappear after a certain period of time inside the body, including bioresorbable active electronics, have been highlighted recently. This review first discusses the historical background of medical implants and briefly define related terminology. Representative examples of non-degradable medical implants for passive structural support and/or for diagnosis and therapy with active electronics are also provided. Then, recent progress in bioresorbable active implants composed of biosignal sensors, actuators for therapeutics, wireless power supply components, and their integrated systems are reviewed. Finally, clinical applications of these bioresorbable electronic implants are exemplified with brief conclusion and future outlook.

Reverse-micelle-induced porous pressure-sensitive rubber for wearable human-machine interfaces.

A novel method to produce porous pressure-sensitive rubber is developed. For the controlled size distribution of embedded micropores, solution-based procedures using reverse micelles are adopted. The piezosensitivity of the pressure sensitive rubber is significantly increased by introducing micropores. Using this method, wearable human-machine interfaces are fabricated, which can be applied to the remote control of a robot.

Epidermal electronics.

We report classes of electronic systems that achieve thicknesses, effective elastic moduli, bending stiffnesses, and areal mass densities matched to the epidermis. Unlike traditional wafer-based technologies, laminating such devices onto the skin leads to conformal contact and adequate adhesion based on van der Waals interactions alone, in a manner that is mechanically invisible to the user. We describe systems incorporating electrophysiological, temperature, and strain sensors, as well as transistors, light-emitting diodes, photodetectors, radio frequency inductors, capacitors, oscillators, and rectifying diodes. Solar cells and wireless coils provide options for power supply. We used this type of technology to measure electrical activity produced by the heart, brain, and skeletal muscles and show that the resulting data contain sufficient information for an unusual type of computer game controller.

Stretchable, curvilinear electronics based on inorganic materials.

All commercial forms of electronic/optoelectronic technologies use planar, rigid substrates. Device possibilities that exploit bio-inspired designs or require intimate integration with the human body demand curvilinear shapes and/or elastic responses to large strain deformations. This article reviews progress in research designed to accomplish these outcomes with established, high-performance inorganic electronic materials and modest modifications to conventional, planar processing techniques. We outline the most well developed strategies and illustrate their use in demonstrator devices that exploit unique combinations of shape, mechanical properties and electronic performance. We conclude with an outlook on the challenges and opportunities for this emerging area of materials science and engineering.