Advanced materials for implantable neuroelectronics.

Materials innovation has arguably played one of the most important roles in the development of implantable neuroelectronics. Such technologies explore biocompatible working systems for reading, triggering, and manipulating neural signals for neuroscience research and provide the additional potential to develop devices for medical diagnostics and/or treatment. The past decade has witnessed a golden era in neuroelectronic materials research. For example, R&D on soft material-based devices have exploded and taken center stage for many applications, including both central and peripheral nerve interfaces. Recent developments have also witnessed the emergence of biodegradable and multifunctional devices. In this article, we aim to overview recent advances in implantable neuroelectronics with an emphasis on chronic biocompatibility, biodegradability, and multifunctionality. In addition to highlighting fundamental materials innovations, we also discuss important challenges and future opportunities.

Development of Organic/Inorganic Hybrid Materials for Fully Degradable Reactive Oxygen Species-Releasing Stents for Antirestenosis.

Despite innovative advances in stent technology, restenosis remains a crucial issue for the clinical implantation of stents. Reactive oxygen species (ROS) are known to potentially accelerate re-endothelialization and lower the risk of restenosis by selectively controlling endothelial cells and smooth muscle cells. Recently, several studies have been conducted to develop biodegradable polymeric stents. As biodegradable polymers are not electrically conductive, double metallic layers are required to constitute a galvanic couple for ROS generation. Here, we report a new biodegradable hybrid material composed of a biodegradable polymer substrate and double anodic/cathodic metallic layers for enhancing re-endothelialization and suppressing restenosis. Pure Zn and Mg films (3 µm thick) were deposited onto poly-l-lactic acid (PLLA) substrates by DC magnetron sputtering, and a long-term immersion test using biodegradable hybrid materials was performed in phosphate-buffered solution (PBS) for 2 weeks. The concentrations of superoxide anions and hydrogen peroxide generated by the corrosion of biodegradable metallic films were monitored every 1 or 2 days. Both superoxide anions and hydrogen peroxide were seamlessly generated even after the complete consumption of the anodic Mg layer. It was confirmed that the superoxide anions and hydrogen peroxide were formed not only by the galvanic corrosion between the anode and cathode layers but also by the corrosion of a single Mg or Zn layer. The corrosion products of the Mg and Zn films in PBS were phosphate, oxide, or chloride of the biodegradable metals. Thus, it is concluded that ROS generation by the corrosion of PLLA-based hybrid materials can be sustained until the exhaustion of the cathode metal layer.

Bioresorbable silicon electronic sensors for the brain.

Many procedures in modern clinical medicine rely on the use of electronic implants in treating conditions that range from acute coronary events to traumatic injury. However, standard permanent electronic hardware acts as a nidus for infection: bacteria form biofilms along percutaneous wires, or seed haematogenously, with the potential to migrate within the body and to provoke immune-mediated pathological tissue reactions. The associated surgical retrieval procedures, meanwhile, subject patients to the distress associated with re-operation and expose them to additional complications. Here, we report materials, device architectures, integration strategies, and in vivo demonstrations in rats of implantable, multifunctional silicon sensors for the brain, for which all of the constituent materials naturally resorb via hydrolysis and/or metabolic action, eliminating the need for extraction. Continuous monitoring of intracranial pressure and temperature illustrates functionality essential to the treatment of traumatic brain injury; the measurement performance of our resorbable devices compares favourably with that of non-resorbable clinical standards. In our experiments, insulated percutaneous wires connect to an externally mounted, miniaturized wireless potentiostat for data transmission. In a separate set-up, we connect a sensor to an implanted (but only partially resorbable) data-communication system, proving the principle that there is no need for any percutaneous wiring. The devices can be adapted to sense fluid flow, motion, pH or thermal characteristics, in formats that are compatible with the body's abdomen and extremities, as well as the deep brain, suggesting that the sensors might meet many needs in clinical medicine.

Relation between blood pressure and pulse wave velocity for human arteries.

Continuous monitoring of blood pressure, an essential measure of health status, typically requires complex, costly, and invasive techniques that can expose patients to risks of complications. Continuous, cuffless, and noninvasive blood pressure monitoring methods that correlate measured pulse wave velocity (PWV) to the blood pressure via the Moens-Korteweg (MK) and Hughes Equations, offer promising alternatives. The MK Equation, however, involves two assumptions that do not hold for human arteries, and the Hughes Equation is empirical, without any theoretical basis. The results presented here establish a relation between the blood pressure P and PWV that does not rely on the Hughes Equation nor on the assumptions used in the MK Equation. This relation degenerates to the MK Equation under extremely low blood pressures, and it accurately captures the results of in vitro experiments using artificial blood vessels at comparatively high pressures. For human arteries, which are well characterized by the Fung hyperelastic model, a simple formula between P and PWV is established within the range of human blood pressures. This formula is validated by literature data as well as by experiments on human subjects, with applicability in the determination of blood pressure from PWV in continuous, cuffless, and noninvasive blood pressure monitoring systems.

Advanced Materials and Devices for Bioresorbable Electronics.

Recent advances in materials chemistry establish the foundations for unusual classes of electronic systems, characterized by their ability to fully or partially dissolve, disintegrate, or otherwise physically or chemically decompose in a controlled fashion after some defined period of stable operation. Such types of "transient" technologies may enable consumer gadgets that minimize waste streams associated with disposal, implantable sensors that disappear harmlessly in the body, and hardware-secure platforms that prevent unwanted recovery of sensitive data. This second area of opportunity, sometimes referred to as bioresorbable electronics, is of particular interest due to its ability to provide diagnostic or therapeutic function in a manner that can enhance or monitor transient biological processes, such as wound healing, while bypassing risks associated with extended device load on the body or with secondary surgical procedures for removal. Early chemistry research established sets of bioresorbable materials for substrates, encapsulation layers, and dielectrics, along with several options in organic and bio-organic semiconductors. The subsequent realization that nanoscale forms of device-grade monocrystalline silicon, such as silicon nanomembranes (m-Si NMs, or Si NMs) undergo hydrolysis in biofluids to yield biocompatible byproducts over biologically relevant time scales advanced the field by providing immediate routes to high performance operation and versatile, sophisticated levels of function. When combined with bioresorbable conductors, dielectrics, substrates, and encapsulation layers, Si NMs provide the basis for a broad, general class of bioresorbable electronics. Other properties of Si, such as its piezoresistivity and photovoltaic properties, allow other types of bioresorbable devices such as solar cells, strain gauges, pH sensors, and photodetectors. The most advanced bioresorbable devices now exist as complete systems with successful demonstrations of clinically relevant modes of operation in animal models. This Account highlights the foundational materials concepts for this area of technology, starting with the dissolution chemistry and reaction kinetics associated with hydrolysis of Si NMs as a function of temperature, pH, and ion and protein concentration. A following discussion focuses on key supporting materials, including a range of dielectrics, metals, and substrates. As comparatively low performance alternatives to Si NMs, bioresorbable organic semiconductors are also presented, where interest derives from their intrinsic flexibility, low-temperature processability, and ease of chemical modification. Representative examples of encapsulation materials and strategies in passive and active control of device lifetime are then discussed, with various device illustrations. A final section outlines bioresorbable electronics for sensing of various biophysical parameters, monitoring electrophysiological activity, and delivering drugs in a programmed manner. Fundamental research in chemistry remains essential to the development of this emerging field, where continued advances will increase the range of possibilities in sensing, actuation, and power harvesting. Materials for encapsulation layers that can delay water-diffusion and dissolution of active electronics in passively or actively triggered modes are particularly important in addressing areas of opportunity in clinical medicine, and in secure systems for envisioned military and industrial uses. The deep scientific content and the broad range of application opportunities suggest that research in transient electronic materials will remain a growing area of interest to the chemistry community.

Stretchable multichannel antennas in soft wireless optoelectronic implants for optogenetics.

Optogenetic methods to modulate cells and signaling pathways via targeted expression and activation of light-sensitive proteins have greatly accelerated the process of mapping complex neural circuits and defining their roles in physiological and pathological contexts. Recently demonstrated technologies based on injectable, microscale inorganic light-emitting diodes (µ-ILEDs) with wireless control and power delivery strategies offer important functionality in such experiments, by eliminating the external tethers associated with traditional fiber optic approaches. Existing wireless µ-ILED embodiments allow, however, illumination only at a single targeted region of the brain with a single optical wavelength and over spatial ranges of operation that are constrained by the radio frequency power transmission hardware. Here we report stretchable, multiresonance antennas and battery-free schemes for multichannel wireless operation of independently addressable, multicolor µ-ILEDs with fully implantable, miniaturized platforms. This advance, as demonstrated through in vitro and in vivo studies using thin, mechanically soft systems that separately control as many as three different µ-ILEDs, relies on specially designed stretchable antennas in which parallel capacitive coupling circuits yield several independent, well-separated operating frequencies, as verified through experimental and modeling results. When used in combination with active motion-tracking antenna arrays, these devices enable multichannel optogenetic research on complex behavioral responses in groups of animals over large areas at low levels of radio frequency power (<1 W). Studies of the regions of the brain that are involved in sleep arousal (locus coeruleus) and preference/aversion (nucleus accumbens) demonstrate the unique capabilities of these technologies.

Bioresorbable silicon electronics for transient spatiotemporal mapping of electrical activity from the cerebral cortex.

Bioresorbable silicon electronics technology offers unprecedented opportunities to deploy advanced implantable monitoring systems that eliminate risks, cost and discomfort associated with surgical extraction. Applications include postoperative monitoring and transient physiologic recording after percutaneous or minimally invasive placement of vascular, cardiac, orthopaedic, neural or other devices. We present an embodiment of these materials in both passive and actively addressed arrays of bioresorbable silicon electrodes with multiplexing capabilities, which record in vivo electrophysiological signals from the cortical surface and the subgaleal space. The devices detect normal physiologic and epileptiform activity, both in acute and chronic recordings. Comparative studies show sensor performance comparable to standard clinical systems and reduced tissue reactivity relative to conventional clinical electrocorticography (ECoG) electrodes. This technology offers general applicability in neural interfaces, with additional potential utility in treatment of disorders where transient monitoring and modulation of physiologic function, implant integrity and tissue recovery or regeneration are required.

Porous Silicon Gradient Refractive Index Micro-Optics.

The emergence and growth of transformation optics over the past decade has revitalized interest in how a gradient refractive index (GRIN) can be used to control light propagation. Two-dimensional demonstrations with lithographically defined silicon (Si) have displayed the power of GRIN optics and also represent a promising opportunity for integrating compact optical elements within Si photonic integrated circuits. Here, we demonstrate the fabrication of three-dimensional Si-based GRIN micro-optics through the shape-defined formation of porous Si (PSi). Conventional microfabrication creates Si square microcolumns (SMCs) that can be electrochemically etched into PSi elements with nanoscale porosity along the shape-defined etching pathway, which imparts the geometry with structural birefringence. Free-space characterization of the transmitted intensity distribution through a homogeneously etched PSi SMC exhibits polarization splitting behavior resembling that of dielectric metasurfaces that require considerably more laborious fabrication. Coupled birefringence/GRIN effects are studied by way of PSi SMCs etched with a linear (increasing from edge to center) GRIN profile. The transmitted intensity distribution shows polarization-selective focusing behavior with one polarization focused to a diffraction-limited spot and the orthogonal polarization focused into two laterally displaced foci. Optical thickness-based analysis readily predicts the experimentally observed phenomena, which strongly match finite-element electromagnetic simulations.

Biodegradable elastomers and silicon nanomembranes/nanoribbons for stretchable, transient electronics, and biosensors.

Transient electronics represents an emerging class of technology that exploits materials and/or device constructs that are capable of physically disappearing or disintegrating in a controlled manner at programmed rates or times. Inorganic semiconductor nanomaterials such as silicon nanomembranes/nanoribbons provide attractive choices for active elements in transistors, diodes and other essential components of overall systems that dissolve completely by hydrolysis in biofluids or groundwater. We describe here materials, mechanics, and design layouts to achieve this type of technology in stretchable configurations with biodegradable elastomers for substrate/encapsulation layers. Experimental and theoretical results illuminate the mechanical properties under large strain deformation. Circuit characterization of complementary metal-oxide-semiconductor inverters and individual transistors under various levels of applied loads validates the design strategies. Examples of biosensors demonstrate possibilities for stretchable, transient devices in biomedical applications.

High-resolution patterns of quantum dots formed by electrohydrodynamic jet printing for light-emitting diodes.

Here we demonstrate materials and operating conditions that allow for high-resolution printing of layers of quantum dots (QDs) with precise control over thickness and submicron lateral resolution and capabilities for use as active layers of QD light-emitting diodes (LEDs). The shapes and thicknesses of the QD patterns exhibit systematic dependence on the dimensions of the printing nozzle and the ink composition in ways that allow nearly arbitrary, systematic control when exploited in a fully automated printing tool. Homogeneous arrays of patterns of QDs serve as the basis for corresponding arrays of QD LEDs that exhibit excellent performance. Sequential printing of different types of QDs in a multilayer stack or in an interdigitated geometry provides strategies for continuous tuning of the effective, overall emission wavelengths of the resulting QD LEDs. This strategy is useful to efficient, additive use of QDs for wide ranging types of electronic and optoelectronic devices.

Magnetically Actuated Trigger Transient Soft Actuators Comprising On-Demand Photo-Initiated and Thermo-Degradable Polypropylene Carbonate-Photo-Acid Generator.

Lifetime-reconfigurable soft robots have emerged as a new class of robots, emphasizing the unmet needs of futuristic sustainability and security. Trigger-transient materials that can both actuate and degrade on-demand are crucial for achieving life-reconfigurable soft robots. Here, we propose the use of transient and magnetically actuating materials that can decompose under ultraviolet light and heat, achieved by adding photo-acid generator (PAG) and magnetic particles (Sr-ferrite) to poly(propylene carbonate) (PPC). Chemical and thermal analyses reveal that the mechanism of PPC-PAG decomposition occurs through PPC backbone cleavage by the photo-induced acid. The self-assembled monolayer (SAM) encapsulation of Sr-ferrite preventing the interaction with the PAG allowed the transience of magnetic soft actuators. We demonstrate remotely controllable and degradable magnetic soft kirigami actuators using blocks with various magnetized directions. This study proposes novel approaches for fabricating lifetime-configurable magnetic soft actuators applicable to diverse environments and applications, such as enclosed/sealed spaces and security/military devices.

Three-Dimensionally Printed Expandable Structural Electronics Via Multi-Material Printing Room-Temperature-Vulcanizing (RTV) Silicone/Silver Flake Composite and RTV.

Three-dimensional (3D) printing has various applications in many fields, such as soft electronics, robotic systems, biomedical implants, and the recycling of thermoplastic composite materials. Three-dimensional printing, which was only previously available for prototyping, is currently evolving into a technology that can be utilized by integrating various materials into customized structures in a single step. Owing to the aforementioned advantages, multi-functional 3D objects or multi-material-designed 3D patterns can be fabricated. In this study, we designed and fabricated 3D-printed expandable structural electronics in a substrateless auxetic pattern that can be adapted to multi-dimensional deformation. The printability and electrical conductivity of a stretchable conductor (Ag-RTV composite) were optimized by incorporating a lubricant. The Ag-RTV and RTV were printed in the form of conducting voxels and frame voxels through multi-nozzle printing and were arranged in a negative Poisson's ratio pattern with a missing rib structure, to realize an expandable passive component. In addition, the expandable structural electronics were embedded in a soft actuator via one-step printing, confirming the possibility of fabricating stable interconnections in expanding deformation via a missing rib pattern.

Recent advances in wearable iontronic sensors for healthcare applications.

Iontronic sensors have garnered significant attention as wearable sensors due to their exceptional mechanical performance and the ability to maintain electrical performance under various mechanical stimuli. Iontronic sensors can respond to stimuli like mechanical stimuli, humidity, and temperature, which has led to exploration of their potential as versatile sensors. Here, a comprehensive review of the recent researches and developments on several types of iontronic sensors (e.g., pressure, strain, humidity, temperature, and multi-modal sensors), in terms of their sensing principles, constituent materials, and their healthcare-related applications is provided. The strategies for improving the sensing performance and environmental stability of iontronic sensors through various innovative ionic materials and structural designs are reviewed. This review also provides the healthcare applications of iontronic sensors that have gained increased feasibility and broader applicability due to the improved sensing performance. Lastly, outlook section discusses the current challenges and the future direction in terms of the applicability of the iontronic sensors to the healthcare.

Fast and Durable Nanofiber Mat Channel Organic Electrochemical Transistors.

Bioelectronic devices that offer real-time measurements, biological signal processing, and continuous monitoring while maintaining stable performance are in high demand. The materials used in organic electrochemical transistors (OECTs) demonstrate high transconductance (GM) and excellent biocompatibility, making them suitable for bioelectronics in a biological environment. However, ion migration in OECTs induces a delayed response time and low cut-off frequency, and the adverse biological environment causes OECT durability problems. Herein, we present OECTs with a faster response time and improved durability, made possible by using a nanofiber mat channel of a conventional OECT structure. Poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS)/polyacrylamide (PAAm) nanofiber mat channel OECTs are fabricated and subjected to various durability tests for the first time based on continuous measurements and mechanical stability assessments. The results indicate that the nanofiber mat channel OECTs have a faster response time and longer life spans compared to those of film channel OECTs. The improvements can be attributed to the increased surface area and fibrous structure of the nanofiber mat channel. Furthermore, the hydrogel helps to maintain the structure of the nanofiber, facilitates material exchange, and eliminates the need for a crosslinker.

Electroceuticals for Regeneration of Long Nerve Gap Using Biodegradable Conductive Conduits and Implantable Wireless Stimulator.

Regeneration of over 10 mm long peripheral nerve defects remains a challenge due to the failure of regeneration by prolonged axotomy and denervation occurring in long-term recovery. Recent studies reveal that conductive conduits and electrical stimulation accelerate the regeneration of long nerve defects. In this study, an electroceutical platform combining a fully biodegradable conductive nerve conduit and a wireless electrical stimulator is proposed to maximize the therapeutic effect on nerve regeneration. Fully biodegradable nerve conduit fabricated using molybdenum (Mo) microparticles and polycaprolactone (PCL) can eliminate the unwanted effects of non-degradable implants, which occupy nerve paths and need to be removed through surgery increasing the risk of complications. The electrical and mechanical properties of Mo/PCL conduits are optimized by controlling the amounts of Mo and tetraglycol lubricant. The dissolution behavior and electrical conductivity of biodegradable nerve conduits in the biomimetic solutions are also evaluated. In in vivo experiments, the integrated strategy of a conductive Mo/PCL conduit with controlled therapeutic electrical stimulation shows accelerated axon regeneration for long sciatic nerve defects in rats compared to the use of the Mo/PCL conduit without stimulation and has a significant therapeutic effect based on the results obtained from the functional recovery test.

Highly Elastic and Conductive Metallic Interconnect with Crystalline-Amorphous Nanolaminate.

Nanolaminate with alternating layers of nanocrystalline Cu and amorphous CuZrTi is suggested as highly stretchable and conductive interconnect material in stretchable devices. 50 nm nanocrystalline Cu and 20 nm amorphous CuZrTi are the optimum thicknesses of the constituent layers, which result in an elastic deformation limit of 3.33% similar to that of the monolithic amorphous CuZrTi film and an electrical conductivity of 11.83 S/µm corresponding to 70% of that of the monolithic nanocrystalline Cu film. The enhanced elastic deformability and conductivity of the nanolaminates enable the maintenance of the interconnect performance for cyclic stretching with a tensile strain of 114% in the form of a free-standing serpentine structure and a tensile strain of 30% in the form of an ordinary circular coil on an elastomer substrate.

Lifetime-configurable soft robots via photodegradable silicone elastomer composites.

Developing soft robots that can control their own life cycle and degrade on-demand while maintaining hyperelasticity is a notable research challenge. On-demand degradable soft robots, which conserve their original functionality during operation and rapidly degrade under specific external stimulation, present the opportunity to self-direct the disappearance of temporary robots. This study proposes soft robots and materials that exhibit excellent mechanical stretchability and can degrade under ultraviolet light by mixing a fluoride-generating diphenyliodonium hexafluorophosphate with a silicone resin. Spectroscopic analysis revealed the mechanism of Si─O─Si backbone cleavage using fluoride ion (F-) and thermal analysis indicated accelerated decomposition at elevated temperatures. In addition, we demonstrated a robotics application by fabricating electronics integrated gaiting robot and a fully closed-loop trigger disintegration robot for autonomous, application-oriented functionalities. This study provides a simple yet novel strategy for designing life cycle mimicking soft robotics that can be applied to reduce soft robotics waste, explore hazardous areas, and ensure hardware security with on-demand destructive material platforms.

A Personalized Electronic Tattoo for Healthcare Realized by On-the-Spot Assembly of an Intrinsically Conductive and Durable Liquid-Metal Composite.

Conventional electronic (e-) skins are a class of thin-film electronics mainly fabricated in laboratories or factories, which is incapable of rapid and simple customization for personalized healthcare. Here a new class of e-tattoos is introduced that can be directly implemented on the skin by facile one-step coating with various designs at multi-scale depending on the purpose of the user without a substrate. An e-tattoo is realized by attaching Pt-decorated carbon nanotubes on gallium-based liquid-metal particles (CMP) to impose intrinsic electrical conductivity and mechanical durability. Tuning the CMP suspension to have low-zeta potential, excellent wettability, and high-vapor pressure enables conformal and intimate assembly of particles directly on the skin in 10 s. Low-cost, ease of preparation, on-skin compatibility, and multifunctionality of CMP make it highly suitable for e-tattoos. Demonstrations of electrical muscle stimulators, photothermal patches, motion artifact-free electrophysiological sensors, and electrochemical biosensors validate the simplicity, versatility, and reliability of the e-tattoo-based approach in biomedical engineering.

Long-term results after modified Brostrom procedure without calcaneofibular ligament reconstruction.

BACKGROUND: The short-term results of modified Brostrom procedures (MBP) have been satisfactory. However, the long-term results of anatomical reconstruction have been less frequently reported. We report on our long-term results in our patient group. MATERIALS AND METHODS: Thirty patients with chronic ankle instability who were treated using the MBP without CFL reconstruction from March 1997 to June 1999 were evaluated retrospectively. This consecutive series of patients was comprised of 26 males and four females. The mean age of the patients at the time of operation was 23 years. The mean followup period was 10.6 years. Twenty-four of the 30 were high-level amateur or professional athletes. The operation procedure involved only ATFL imbrication with inferior extensor retinaculum (IER) reinforcement. Clinical outcomes were evaluated by reviewing clinical charts, retrospectively. Functional outcome scores were obtained using the Hamilton scale, a VAS, and AOFAS score at final followup visit, when each patient underwent a physical examination and stress radiography. RESULTS: Mean AOFAS score was 91 and the mean VAS at final followup was 87. According to the Hamilton classification, 12 achieved an excellent result, 16 a good result, and two a fair result. Mean anterior translation values at final followup were 6.9 and 6.1 mm on ipsilateral and contralateral sides. Furthermore, mean talar tilt angles were 3.0 and 2.5 degrees for ipsilateral and contralateral sides. Twenty-eight of the 30 patients were restored to pre-injury activity levels. CONCLUSION: The long-term surgical results of the MBP without CFL reconstruction for chronic lateral ankle instability were good to excellent in terms of functional, clinical, and radiographic assessments.

Principles for Controlling the Shape Recovery and Degradation Behavior of Biodegradable Shape-Memory Polymers in Biomedical Applications.

Polymers with the shape memory effect possess tremendous potential for application in diverse fields, including aerospace, textiles, robotics, and biomedicine, because of their mechanical properties (softness and flexibility) and chemical tunability. Biodegradable shape memory polymers (BSMPs) have unique benefits of long-term biocompatibility and formation of zero-waste byproducts as the final degradable products are resorbed or absorbed via metabolism or enzyme digestion processes. In addition to their application toward the prevention of biofilm formation or internal tissue damage caused by permanent implant materials and the subsequent need for secondary surgery, which causes secondary infections and complications, BSMPs have been highlighted for minimally invasive medical applications. The properties of BSMPs, including high tunability, thermomechanical properties, shape memory performance, and degradation rate, can be achieved by controlling the combination and content of the comonomer and crystallinity. In addition, the biodegradable chemistry and kinetics of BSMPs, which can be controlled by combining several biodegradable polymers with different hydrolysis chemistry products, such as anhydrides, esters, and carbonates, strongly affect the hydrolytic activity and erosion property. A wide range of applications including self-expending stents, wound closure, drug release systems, and tissue repair, suggests that the BSMPs can be applied as actuators on the basis of their shape recovery and degradation ability.