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Giant electrical conductivity difference enabled liquid metal-hydrogel hybrid printed circuits for soft bioelectronics
Acute and chronic wounds have long posed significant global health challenges. In recent years, electrophysiological strategies for wound healing have attracted considerable interest. Notably, substantial efforts have been directed toward...
Indium has attracted significant attention in thermal management applications due to its low melting point, high thermal conductivity, and ductility. However, the wetting behavior between indium and nickel or its alloys, commonly used as bonding layers, is often suboptimal in soldering applications. This study investigates the high-temperature wetting behavior and intermetallic compound (IMC) growth between indium and NiCu alloy layers. NiCu alloy layers were successfully electroplated, ensuring uniform thickness and smooth surfaces. Nano-thick wetting layers of Cu, Ag, and Au were applied to improve wetting. The wetting behavior of indium on NiCu, Cu-coated NiCu, Ag-coated NiCu, and Au-coated NiCu was studied within a temperature range of 200-300°C. Contact angles and spreading diameters were measured, revealing a contact angle of 90° on the NiCu alloy. On the Au-coated NiCu surface, indium exhibited super-wetting properties with a contact angle of just 24.2°. Scanning electron microscopy (SEM) characterized the IMC and precursor films at the interface. Indium showed reactive wetting on NiCu, and when an Au layer was applied, the IMC extended beyond the three-phase contact line. This study provides valuable insights for improving heat dissipation in high-power-density devices using indium.
Stretchable conductors are a class of electronics characterized by their significant deformability and have emerged as essential components for the next generation of electronic devices. However, significant conductivity reduction under stretching poses a limitation for their application across various fields. Liquid metals, as conductors possessing both high electrical conductivity and fluidity, provide an ideal solution to this challenge, facilitating the development of stretchable conductors with enhanced electrical stability. The present review, aiming at providing guidance and stimulating research enthusiasm for future research, delivers a comprehensive overview of the design, fabrication, and applications of liquid metal-based stretchable conductors (LMSCs). First, the prevalent fabrication methods for constructing LMSCs are presented, followed by a discussion on the key performances of LMSCs, wherein the principles vital for achieving high electrical stability are thoroughly discussed. Then, several representative applications of LMSCs are illustrated. Finally, this review makes a brief discussion on the current challenges and future development of LMSCs.
Traditional public health systems suffer from incomprehensive, delayed, and inefficient medical services. Convenient and comprehensive health monitoring has been highly sought after recently. Flexible and wearable devices are attracting wide attention due to their potential applications in wearable human health monitoring and care systems. Using carbon materials with overall superiorities can facilitate the development of wearable and flexible devices with various functions and excellent performance, which can comprehensively and real‐time monitor human health status and prevent diseases. Herein, the latest advances in the rational design and controlled fabrication of carbon materials for applications in health‐related flexible and wearable electronics are reviewed. The fabrication strategies, working mechanism, performance, and applications in health monitoring of carbon‐based flexible devices, including electromechanical sensors, temperature/humidity sensors, chemical sensors, and flexible conductive wires/electrodes, are reviewed. Furthermore, integrating multiple carbon‐based devices into multifunctional wearable systems is discussed. Finally, the existing challenges and future opportunities in this field are also proposed.
Electronics based on hydrogels can have inherent similarities to biological tissue and are of potential use in biomedical applications. Ideally, such hydrogel electronics should offer customizable three-dimensional circuits, but making complex three-dimensional circuits encapsulated within a hydrogel matrix is challenging with existing materials and manufacturing methods. Here we report the three-dimensional printing of hydrogel electronics using a curable hydrogel-based supporting matrix and a stretchable silver–hydrogel ink. The supporting matrix has a yield stress fluid behaviour, so the shear force generated by a moving printer nozzle creates a temporary fluid-like state, allowing the accurate placement in the matrix of silver–hydrogel ink circuits and electronic components. After printing, the entire matrix and embedded circuitry can be cured at 60 °C to form soft (Young’s modulus of less than 5 kPa) and stretchable (elongation of around 18) monolithic hydrogel electronics, whereas the conductive ink exhibits a high conductivity of around 1.4 × 103 S cm−1. We use our three-dimensional printing approach to create strain sensors, inductors and biological electrodes. Using a conductive silver–hydrogel ink, three-dimensional circuits can be printed into a supporting hydrogel matrix that has a temporary, fluid-like state before curing to make fully encapsulated hydrogel electronics.
Recent years have witnessed the rapid development of sustainable materials. Along this line, developing biodegradable or recyclable soft electronics is challenging yet important due to their versatile applications in biomedical devices, soft robots, and wearables. Although some degradable bulk hydrogels are directly used as the soft electronics, the sensing performances are usually limited due to the absence of distributed conducting circuits. Here, sustainable hydrogel‐based soft electronics (HSE) are reported that integrate sensing elements and patterned liquid metal (LM) in the gelatin–alginate hybrid hydrogel. The biopolymer hydrogel is transparent, robust, resilient, and recyclable. The HSE is multifunctional; it can sense strain, temperature, heart rate (electrocardiogram), and pH. The strain sensing is sufficiently sensitive to detect a human pulse. In addition, the device serves as a model system for iontophoretic drug delivery by using patterned LM as the soft conductor and electrode. Noncontact detection of nearby objects is also achieved based on electrostatic‐field‐induced voltage. The LM and biopolymer hydrogel are healable, recyclable, and degradable, favoring sustainable applications and reconstruction of the device with new functions. Such HSE with multiple functions and favorable attributes should open opportunities in next‐generation electronic skins and hydrogel machines.
Hydrogel-based flexible electronics have been of widespread interest in recent years. However, current hydrogel electronics have limitations, such as poor biocompatibility, non-reusability, low electrical response to deformation and being single-function. GelMA is a gelatin-based hydrogel that has been widely used in the biological field, such as in tissue repair and drug delivery. Could it be a good choice for high biocompatibility wearable electronics? Here, by controlling the replacement rate of amine and hydroxy functionalities, we made the common brittle GelMA into a highly stretchable hydrogel. And we report for the first time GelMA hydrogel electronics with liquid metals (LMGE), which could be fabricated by simply injecting liquid metals into the internal microchannels of the GelMA hydrogels (GelMA-30). With the unique biocompatibility, outstanding air and ion permeability, and great mechanical properties of GelMA-30, as well as the low toxicity, high conductivity and high rheology of liquid metals, LMGE can not only monitor movement changes and even the heartbeat of rats, but can also be used as a wireless monitor to supervise secretions produced during human exercise. The design of LMGE provides a general strategy for the manufacture of bio-flexible hydrogel electronics, which opens the way for the development of multi-functional biomimetic materials for integrated monitoring and repair for biomedical applications.
Heart diseases are currently the leading cause of death worldwide. The ability to create cardiovascular tissue has numerous applications in understanding tissue development, disease progression, pharmacological testing, bio‐actuators, and transplantation; yet current cardiovascular tissue engineering (CTE) methods are limited. However, there have been emerging developments in the bioelectronics field, with the creation of biomimetic devices that can intimately interact with cardiac cells, provide monitoring capabilities, and regulate tissue formation. Combining bioelectronics with cardiac tissue engineering can overcome current limitations and produce physiologically relevant tissue that can be used in various areas of cardiovascular research and medicine. This review highlights the recent advances in cardiovascular‐based bioelectronics. First, cardiac tissue engineering and the potential of bioelectronic therapies for cardiovascular diseases are discussed. Second, advantageous bioelectronic materials for CTE and implantation and their properties are reviewed. Third, several representative cardiovascular tissue‐bioelectronic interface models and the beneficial functions that bioelectronics can demonstrate in in vitro and in vivo applications are explored. Finally, the prospects and remaining challenges for clinical application are discussed.
Gallium (Ga)‐based liquid metal materials have emerged as a promising material platform for soft bioelectronics. Unfortunately, Ga has limited biostability and electrochemical performance under physiological conditions, which can hinder the implementation of its use in bioelectronic devices. Here, an effective conductive polymer deposition strategy on the liquid metal surface to improve the biostability and electrochemical performance of Ga‐based liquid metals for use under physiological conditions is demonstrated. The conductive polymer [poly(3,4‐ethylene dioxythiophene):tetrafluoroborate]‐modified liquid metal surface significantly outperforms the liquid metal.based electrode in mechanical, biological, and electrochemical studies. In vivo action potential recordings in behaving nonhuman primate and invertebrate models demonstrate the feasibility of using liquid metal electrodes for high‐performance neural recording applications. This is the first demonstration of single‐unit neural recording using Ga‐based liquid metal bioelectronic devices to date. The results determine that the electrochemical deposition of conductive polymer over liquid metal can improve the material properties of liquid metal electrodes for use under physiological conditions and open numerous design opportunities for next‐generation liquid metal‐based bioelectronics.
Soft electronics are rising electronic technologies towards applications spanning from healthcare monitoring to medical implants. However, poor adhesion strength and significant mechanical mismatches inevitably cause the interface failure of devices. Herein we report a self-adhesive conductive polymer that possesses low modulus (56.1-401.9 kPa), high stretchability (700%), high interfacial adhesion (lap-shear strength >1.2 MPa), and high conductivity (1-37 S/cm). The self-adhesive conductive polymer is fabricated by doping the poly(3,4-ethylenedioxythiophene): poly(styrene sulfonate) composite with a supramolecular solvent (β-cyclodextrin and citric acid). We demonstrated the solution process-based fabrication of self-adhesive conductive polymer-based electrodes for various soft devices, including alternating current electroluminescent devices, electromyography monitoring, and an integrated system for the visualization of electromyography signals during muscle training with an array of alternating current electroluminescent devices. The self-adhesive conductive polymer-based electronics show promising features to further develop wearable and comfortable bioelectronic devices with the physiological electric signals of the human body readable and displayable during daily activities.
Optoelectronic biointerfaces have made a significant impact on modern science and technology from understanding the mechanisms of the neurotransmission to the recovery of the vision for blinds. They are based on the cell interfaces made of organic or inorganic materials such as silicon, graphene, oxides, quantum dots, and π‐conjugated polymers, which are dry and stiff unlike a cell/tissue environment. On the other side, wet and soft hydrogels have recently been started to attract significant attention for bioelectronics because of its high‐level tissue‐matching biomechanics and biocompatibility. However, it is challenging to obtain optimal opto‐bioelectronic devices by using hydrogels requiring device, heterojunction, and hydrogel engineering. Here, an optoelectronic biointerface integrated with a poly(3,4‐ethylenedioxythiophene):poly(styrene sulfonate), PEDOT:PSS, hydrogel that simultaneously achieves efficient, flexible, stable, biocompatible, and safe photostimulation of cells is demonstrated. Besides their interfacial tissue‐like biomechanics, ≈34 kPa, and high‐level biocompatibility, hydrogel‐integration facilitates increase in charge injection amounts sevenfolds with an improved responsivity of 156 mA W⁻¹, stability under mechanical bending , and functional lifetime over three years. Finally, these devices enable stimulation of individual hippocampal neurons and photocontrol of beating frequency of cardiac myocytes via safe charge‐balanced capacitive currents. Therefore, hydrogel‐enabled optoelectronic biointerfaces hold great promise for next‐generation wireless neural and cardiac implants.
Recent advances in nanostructured materials and unconventional device designs have transformed the bioelectronics from a rigid and bulky form into a soft and ultrathin form and brought enormous advantages to the bioelectronics. For example, mechanical deformability of the soft bioelectronics and thus its conformal contact onto soft curved organs such as brain, heart, and skin have allowed researchers to measure high-quality biosignals, deliver real-time feedback treatments, and lower long-term side-effects in vivo. Here, we review various materials, fabrication methods, and device strategies for flexible and stretchable electronics, especially focusing on soft biointegrated electronics using nanomaterials and their composites. First, we summarize top-down material processing and bottom-up synthesis methods of various nanomaterials. Next, we discuss state-of-the-art technologies for intrinsically stretchable nanocomposites composed of nanostructured materials incorporated in elastomers or hydrogels. We also briefly discuss unconventional device design strategies for soft bioelectronics. Then individual device components for soft bioelectronics, such as biosensing, data storage, display, therapeutic stimulation, and power supply devices, are introduced. Afterward, representative application examples of the soft bioelectronics are described. A brief summary with a discussion on remaining challenges concludes the review.
In the booming development of flexible electronics represented by electronic skins, soft robots, and human–machine interfaces, 3D printing of hydrogels, an approach used by the biofabrication community, is drawing attention from researchers working on hydrogel‐based stretchable ionotronic devices. Such devices can greatly benefit from the excellent patterning capability of 3D printing in three dimensions, as well as the free design complexity and easy upscale potential. Compared to the advanced stage of 3D bioprinting, 3D printing of hydrogel ionotronic devices is in its infancy due to the difficulty in balancing printability, ionic conductivity, shape fidelity, stretchability, and other functionalities. In this review, a guideline is provided on how to utilize the power of 3D printing in building high‐performance hydrogel‐based stretchable ionotronic devices mainly from a materials’ point of view, highlighting the systematic approach to balancing the printability, printing quality, and performance of printed devices. Various 3D printing methods for hydrogels are introduced, and then the ink design principles, balancing printing quality, printed functions, such as elastic conductivity, self‐healing ability, and device (e.g., flexible sensors, shape‐morphing actuators, soft robots, electroluminescent devices, and electrochemical biosensors) performances are discussed. In conclusion, perspectives on the future directions of this exciting field are presented. Hydrogel ionotronics prepared by 3D printing have received intensive attention due to the combination of high biocompatibility, stimuli‐responsiveness, rapid prototyping, and delicated patterns. Herein, recent advances of 3D printed hydrogel devices are reviewed, highlighting strategies to enhance printing quality (printability, resolution, and shape fidelity), properties (elastic conductivity, and self‐healing ability), and performances of various ionotronic devices.
A closed‐loop system that can mini‐invasively track blood glucose and intelligently treat diabetes is in great demand for modern medicine, yet it remains challenging to realize. Microneedles technologies have recently emerged as powerful tools for transdermal applications with inherent painlessness and biosafety. In this work, for the first time to the authors' knowledge, a fully integrated wearable closed‐loop system (IWCS) based on mini‐invasive microneedle platform is developed for in situ diabetic sensing and treatment. The IWCS consists of three connected modules: 1) a mesoporous microneedle‐reverse iontophoretic glucose sensor; 2) a flexible printed circuit board as integrated and control; and 3) a microneedle‐iontophoretic insulin delivery component. As the key component, mesoporous microneedles enable the painless penetration of stratum corneum, implementing subcutaneous substance exchange. The coupling with iontophoresis significantly enhances glucose extraction and insulin delivery and enables electrical control. This IWCS is demonstrated to accurately monitor glucose fluctuations, and responsively deliver insulin to regulate hyperglycemia in diabetic rat model. The painless microneedles and wearable design endows this IWCS as a highly promising platform to improve the therapies of diabetic patients.
Nerve injuries and neurodegenerative disorders remain serious challenges, owing to the poor treatment outcomes of in situ neural stem cell regeneration. The most promising treatment for such injuries and disorders is stem cell-based therapies, but there remain obstacles in controlling the differentiation of stem cells into fully functional neuronal cells. Various biochemical and physical approaches have been explored to improve stem cell-based neural tissue engineering, among which electrical stimulation has been validated as a promising one both in vitro and in vivo. Here, we summarize the most basic waveforms of electrical stimulation and the conductive materials used for the fabrication of electroactive substrates or scaffolds in neural tissue engineering. Various intensities and patterns of electrical current result in different biological effects, such as enhancing the proliferation, migration, and differentiation of stem cells into neural cells. Moreover, conductive materials can be used in delivering electrical stimulation to manipulate the migration and differentiation of stem cells and the outgrowth of neurites on two- and three-dimensional scaffolds. Finally, we also discuss the possible mechanisms in enhancing stem cell neural differentiation using electrical stimulation. We believe that stem cell-based therapies using biocompatible conductive scaffolds under electrical stimulation and biochemical induction are promising for neural regeneration.
Hydrogels offer tissue-like compliance, stretchability, fracture toughness, ionic conductivity and compatibility with biological tissues. However, their electrical conductivity (<100 S cm⁻¹) is inadequate for digital circuits and applications in bioelectronics. Furthermore, efforts to increase conductivity by using hydrogel composites with conductive fillers have led to compromises in compliance and deformability. Here, we report a hydrogel composite that has a high electrical conductivity (>350 S cm⁻¹) and is capable of delivering direct current while maintaining soft compliance (Young’s modulus < 1 kPa) and deformability. Micrometre-sized silver flakes are suspended in a polyacrylamide–alginate hydrogel matrix and, after going through a partial dehydration process, the flakes form percolating networks that are electrically conductive and robust to mechanical deformations. To illustrate the capabilities of our silver–hydrogel composite, we use the material in a stingray-inspired swimmer and a neuromuscular electrical stimulation electrode.
Spreading liquid droplets on solid surfaces is a core topic in physical chemistry with significant technological implications. Liquid metals, which are eutectic alloys of constituent metal atoms with low melting temperatures, are practically useful, but difficult to spread on solid surfaces because of their high surface tension. This makes it difficult to use liquid metals as deformable on‐board microcircuitry electrodes, despite their intrinsic deformability. In this study, it is discovered that eutectic gallium–indium (EGaIn) can be spread onto the surface of chemically cross‐linked hydrogels consisting of aliphatic alkyl chains with numerous hydroxyl groups (OH), thus facilitating the development of directly micropatterned EGaIn electrodes. More importantly, EGaIn patterned on a hydrogel autonomously reconciliates its surface to form a firm hydrogel interface upon mechanical deformation of the hydrogel. This autonomous surface reconciliation of EGaIn on hydrogels allows researchers to reap the benefits of chemically modified hydrogels, such as reversible stretching, self‐healing, and water‐swelling capability, thereby facilitating the fabrication of superstretchable, self‐healable, and water‐swellable liquid‐metal electrodes with very high conductance tolerance upon deformation. Such electrodes are suitable for a variety of deformable microelectronic applications.
With the rapid increase in the use of optogenetics to investigate the nervous system, there is a high demand for a neural interface that enables 2D mapping of electrophysiological neural signals with high precision during simultaneous light stimulation. Here, a gold nanonetwork (Au NN)‐based transparent neural electrocorticogram (ECoG) monitoring system is proposed as implantable neural electronics. The neural interface enables accurate 2D mapping of ECoG neural signals without any photoelectric artifact during light stimulation. By using the Au NN, not only the transmittance of the microelectrodes is increased by 81% but also a low electrochemical impedance of 33.9 kΩ at 1 kHz with improved mechanical stability is achieved. It is demonstrated that the transparent microelectrode array records multichannel in vivo neural activities with no photoelectric artifact and a high signal‐to‐noise ratio. Propagation of neural dynamics of optically driven neural activities is also clearly visualized using the 2D Au NN microelectrode array. This transparent, flexible ECoG microelectrode array is a promising candidate for next‐generation in vitro and in vivo neural interface for 2D mapping of neural dynamics.
Abstract Recently, electrical stimulation as a physical stimulus draws lots of attention. It shows great potential in disease treatment, wound healing, and mechanism study because of significant experimental performance. Electrical stimulation can activate many intracellular signaling pathways, and influence intracellular microenvironment, as a result, affect cell migration, cell proliferation, and cell differentiation. Electrical stimulation is using in tissue engineering as a novel type of tool in regeneration medicine. Besides, with the advantages of biocompatible conductive materials coming into view, the combination of electrical stimulation with suitable tissue engineered scaffolds can well combine the benefits of both and is ideal for the field of regenerative medicine. In this review, we summarize the various materials and latest technologies to deliver electrical stimulation. The influences of electrical stimulation on cell alignment, migration and its underlying mechanisms are discussed. Then the effect of electrical stimulation on cell proliferation and differentiation are also discussed.
Hydrogel bioelectronics that can interface biological tissues and flexible electronics is at the core of the growing field of healthcare monitoring, smart drug systems, and wearable and implantable devices. Here, a simple strategy is demonstrated to prototype all‐hydrogel bioelectronics with embedded arbitrary conductive networks using tough hydrogels and liquid metal. Due to their excellent stretchability, the resultant all‐hydrogel bioelectronics exhibits stable electrochemical properties at large tensile stretch and various modes of deformation. The potential of fabricated all‐hydrogel bioelectronics is demonstrated as wearable strain sensors, cardiac patches, and near‐field communication (NFC) devices for monitoring various physiological conditions wirelessly. The presented simple platform paves the way of implantable hydrogel electronics for Internet‐of‐Things and tissue–machine interfacing applications. Stretchable and wireless bioelectronics based on all‐hydrogel microfluidics and liquid metal are fabricated by combining a two‐step crosslinking mechanism and a laser‐engraving method. The perfused liquid metal in hydrogel microchannels form tailor‐designed conductive networks of hydrogel bioelectronics. The applications of all‐hydrogel‐based bioelectronics are demonstrated as wearable and potentially implantable sensors for monitoring physiologically relevant signals wirelessly.
Abstract Substantial effort has been devoted to both scientific and technological developments of wearable, flexible, semitransparent, and sensing electronics (e.g., organic/perovskite photovoltaics, organic thin‐film transistors, and medical sensors) in the past decade. The key to realizing those functionalities is essentially the fabrication of conductive electrodes with desirable mechanical properties. Conductive polymers (CPs) of poly(3,4‐ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) have emerged to be the most promising flexible electrode materials over rigid metallic oxides and play a critical role in these unprecedented devices as transparent electrodes, hole transport layers, interconnectors, electroactive layers, or motion‐sensing conductors. Here, the current status of research on PEDOT:PSS is summarized including various approaches to boosting the electrical conductivity and mechanical compliance and stability, directly linked to the underlying mechanism of the performance enhancements. Along with the basic principles, the most cutting edge‐progresses in devices with PEDOT:PSS are highlighted. Meanwhile, the advantages and plausible problems of the CPs and as‐fabricated devices are pointed out. Finally, new perspectives are given for CP modifications and device fabrications. This work stresses the importance of developing CP films and reveals their critical role in the evolution of these next‐generation devices featuring wearable, deformable, printable, ultrathin, and see‐through characteristics.
Due to inherently poor healable and stretchable features, the most explored polyvinyl alcohol-based gel electrolytes cannot well meet the requirements of stretchable, healable and multifunctional supercapacitors. Here, we report a hydrogel of a copolymer cross-linked by double linkers of Laponite (synthetic hectorite-type clay) and graphene oxide. The resultant hydrogel shows high mechanical stretchability, excellent ionic conductivity, and superior healable performance. Along with designing wrinkled-structure electrodes, supercapacitors fabricated by using this hydrogel as a gel electrolyte not only exhibit ultrahigh mechanical stretchability of 1000%, but also achieve repeated healable performance under treatments of both infrared light irradiation and heating. More significantly, a broken/healed supercapacitor also possesses an ultrahigh stretchability up to 900% with slight performance decay. This hydrogel electrolyte could be easily functionalized by introducing other functional components, and extended for use in other portable and wearable energy related devices with multifunction.
Recording infraslow brain signals (<0.1 Hz) with microelectrodes is severely hampered by current microelectrode materials, primarily due to limitations resulting from voltage drift and high electrode impedance. Hence, most recording systems include high-pass filters that solve saturation issues but come hand in hand with loss of physiological and pathological information. In this work, we use flexible epicortical and intracortical arrays of graphene solution-gated field-effect transistors (gSGFETs) to map cortical spreading depression in rats and demonstrate that gSGFETs are able to record, with high fidelity, infraslow signals together with signals in the typical local field potential bandwidth. The wide recording bandwidth results from the direct field-effect coupling of the active transistor, in contrast to standard passive electrodes, as well as from the electrochemical inertness of graphene. Taking advantage of such functionality, we envision broad applications of gSGFET technology for monitoring infraslow brain activity both in research and in the clinic.
Bioelectronic interfacing with the human body including electrical stimulation and recording of neural activities is the basis of the rapidly growing field of neural science and engineering, diagnostics, therapy, and wearable and implantable devices. Owing to intrinsic dissimilarities between soft, wet, and living biological tissues and rigid, dry, and synthetic electronic systems, the development of more compatible, effective, and stable interfaces between these two different realms has been one of the most daunting challenges in science and technology. Recently, hydrogels have emerged as a promising material candidate for the next-generation bioelectronic interfaces, due to their similarities to biological tissues and versatility in electrical, mechanical, and biofunctional engineering. In this review, we discuss (i) the fundamental mechanisms of tissue-electrode interactions, (ii) hydrogels' unique advantages in bioelectrical interfacing with the human body, (iii) the recent progress in hydrogel developments for bioelectronics, and (iv) rational guidelines for the design of future hydrogel bioelectronics. Advances in hydrogel bioelectronics will usher unprecedented opportunities toward ever-close integration of biology and electronics, potentially blurring the boundary between humans and machines.
The limitations of bone reconstruction techniques have stimulated the tissue engineering for the repair of large bone defects using osteoconductive materials and osteoinductive agents. This study evaluated the effects of low intensity electric current on the inorganic bovine graft in calvaria defects. Bone defects were performed with piezoelectric system in the calvaria of Wistar rats divided into four groups (n = 24): (C) without grafting and without electrical stimulation; (E) with grafting; (MC) without grafting and submitted to electrical stimulation; (MC + E) with grafting and submitted to electrical stimulation. Inflammatory, angiogenic and osteogenic events during bone repair at the 10th, 30th, 60th, and 90th days were considered. Several inflammatory markers demonstrated the efficacy of grafting in reducing inflammation, particularly when subjected to electrical stimulation. Angiogenesis and collagen organization were more evident by electrical stimulation application on the grafts. Moreover, the osteogenic cell differentiation process indicated that the application of microcurrent on grafting modulated the homeostasis of bone remodeling. It is concluded that microcurrent favored the performance of grafts in calvarial rat model. Low‐intensity electrical current might improve the osteoconductive property of grafting in bone defects. Therefore, electrical current becomes an option as complementary therapy in clinical trials involving bone surgeries and injuries. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 924–932, 2019.
Although electrical stimulation is therapeutically applied for neural regeneration in patients, it remains unclear how electrical stimulation exerts its effects at the molecular level on spinal cord injury (SCI). To identify the signaling pathway involved in electrical stimulation improving the function of injured spinal cord, 21 female Sprague-Dawley rats were randomly assigned to three groups: control (no surgical intervention, n = 6), SCI (SCI only, n = 5), and electrical simulation (ES; SCI induction followed by ES treatment, n = 10). A complete spinal cord transection was performed at the 10ththoracic level. Electrical stimulation of the injured spinal cord region was applied for 4 hours per day for 7 days. On days 2 and 7 post SCI, the Touch-Test Sensory Evaluators and the Basso-Beattie-Bresnahan locomotor scale were used to evaluate rat sensory and motor function. Somatosensory-evoked potentials of the tibial nerve of a hind paw of the rat were measured to evaluate the electrophysiological function of injured spinal cord. Western blot analysis was performed to measure p38-RhoA and ERK1/2-Bcl-2 pathways related protein levels in the injured spinal cord. Rat sensory and motor functions were similar between SCI and ES groups. Compared with the SCI group, in the ES group, the latencies of the somatosensory-evoked potential of the tibial nerve of rats were significantly shortened, the amplitudes were significantly increased, RhoA protein level was significantly decreased, protein gene product 9.5 expression, ERK1/2, p38, and Bcl-2 protein levels in the spinal cord were significantly increased. These data suggest that ES can promote the recovery of electrophysiological function of the injured spinal cord through regulating p38-RhoA and ERK1/2-Bcl-2 pathway-related protein levels in the injured spinal cord.
The concept of therapeutic percutaneous neuromodulation has, until recently, been limited by the ability to penetrate deeply enough to stimulate internal organs. By utilizing 2 medium frequency, slightly out of phase electrical currents passing diagonally through the abdomen, a third, low frequency current is created at the point of bisection. This interferential current appears to stimulate nerve fibers in the target organs and may have a therapeutic action. The aim of the study is to review the use of transcutaneous interferential electrical stimulation with a focus on its application in gastroenterology, particularly in motility disorders. Studies involving use of interferential current therapy were searched from Medline, PubMed, and Scopus databases, and articles pertaining to history, its application and all those treating abdominal and gastrointestinal disorders were retrieved. Seventeen studies were identified, 13 involved children only. Eleven of these were randomised controlled trials (3 in adults). Four trials were from the one center, where each paper reported on different outcomes such as soiling, defecation frequency, quality of life, and colon transit studies from the one pool of children. All studies found statistically significant improvement in symptom reduction. However, weaknesses in study design were apparent in some. In particular, finding an adequate placebo to interferential current therapy has been difficult. Interferential current therapy shows potential as a novel, non-pharmacological and economical means of treating gastrointestinal dysfunction such as constipation. More studies are needed particularly in the adult population. However, the design of a suitable placebo is challenging.
Bidirectional interfacing with the nervous system enables neuroscience research, diagnosis, and therapy. This two-way communication allows us to monitor the state of the brain and its composite networks and cells as well as to influence them to treat disease or repair/restore sensory or motor function. To provide the most stable and effective interface, the tools of the trade must bridge the soft, ion-rich, and evolving nature of neural tissue with the largely rigid, static realm of microelectronics and medical instruments that allow for readout, analysis, and/or control. In this Review, we describe how the understanding of neural signaling and material-tissue interactions has fueled the expansion of the available tool set. New probe architectures and materials, nanoparticles, dyes, and designer genetically encoded proteins push the limits of recording and stimulation lifetime, localization, and specificity, blurring the boundary between living tissue and engineered tools. Understanding these approaches, their modality, and the role of cross-disciplinary development will support new neurotherapies and prostheses and provide neuroscientists and neurologists with unprecedented access to the brain.
Glial scar is a significant barrier to neural implant function. Micromotion between the implant and tissue is suspected to be a key driver of glial scar formation around neural implants. This study explores the ability of soft hydrogel coatings to modulate glial scar formation by reducing local strain. PEG hydrogels with controllable thickness and elastic moduli were formed on the surface of neural probes. These coatings significantly reduced the local strain resulting from micromotion around the implants. Coated implants were found to significantly reduce scarring in vivo, compared to hard implants of identical diameter. Increasing implant diameter was found to significantly increase scarring for glass implants, as well as increase local BBB permeability, increase macrophage activation, and decrease the local neural density. These results highlight the tradeoff in mechanical benefit with the size effects from increasing the overall diameter following the addition of a hydrogel coating. This study emphasizes the importance of both mechanical and geometric factors of neural implants on chronic timescales.
Functional recovery after oculomotor nerve injury is very poor. Electrical stimulation has been shown to promote regeneration of injured nerves. We hypothesized that electrical stimulation would improve the functional recovery of injured oculomotor nerves. Oculomotor nerve injury models were created by crushing the right oculomotor nerves of adult dogs. Stimulating electrodes were positioned in both proximal and distal locations of the lesion, and non-continuous rectangular, biphasic current pulses (0.7 V, 5 Hz) were administered 1 hour daily for 2 consecutive weeks. Analysis of the results showed that electrophysiological and morphological recovery of the injured oculomotor nerve was enhanced, indicating that electrical stimulation improved neural regeneration. Thus, this therapy has the potential to promote the recovery of oculomotor nerve dysfunction. © 2016, Editorial Board of Neural Regeneration Research. All rights reserved.
An elastic printed circuit board (E-PCB) is a conductive framework used for the facile assembly of system-level stretchable electronics. E-PCBs require elastic conductors that have high conductivity, high stretchability, tough adhesion to various components, and imperceptible resistance changes even under large strain. We present a liquid metal particle network (LMP Net ) assembled by applying an acoustic field to a solid-state insulating liquid metal particle composite as the elastic conductor. The LMP Net conductor satisfies all the aforementioned requirements and enables the fabrication of a multilayered high-density E-PCB, in which numerous electronic components are intimately integrated to create highly stretchable skin electronics. Furthermore, we could generate the LMP Net in various polymer matrices, including hydrogels, self-healing elastomers, and photoresists, thus showing their potential for use in soft electronics.
Millions of people suffer from tissue diseases and organ dysfunction, such as bone or nerve defects, spinal cord injuries and arrhythmia, which often leads to morbidity and disability. Electrical stimulation as a promising nonpharmacological technique has been proven to be effective in promoting tissue regeneration and functional restoration. Nevertheless, existing clinical electrical therapies are often limited to intraoperative window or percutaneous stimulation that suffer from insufficient time frame and potential infection risks. To overcome these challenges, innovative electrical stimulation implants with miniaturized, self-powered, flexible or biodegradable features have been proposed. This review summarizes recent advances of novel materials strategies and device schemes for tissue regeneration and/or functional restoration of bones, nerves, gastrointestinal tracts, cardiac systems, etc.. Insights on future directions of electrical stimulation devices are given at the end.
Electrical stimulation can facilitate wound healing with high efficiency and limited side effects. However, current electrical stimulation devices have displayed poor conformability and coupling with wounds, due to their bulky nature and the rigidity of electrodes utilized. Here, a flexible electrical patch (ePatch) made with conductive hydrogel as electrodes to improve wound management was reported. The conductive hydrogel was synthesized using silver nanowire (AgNW) and methacrylated alginate (MAA), with the former chosen as the electrode material considering its antibacterial properties, and the latter used due to its clinical suitability in wound healing. The composition of the hydrogel was optimized to enable printing on medical-grade patches for personalized wound treatment. The ePatch was shown to promote re-epithelization, enhance angiogenesis, mediate immune response, and prevent infection development in the wound microenvironment. In vitro studies indicated an elevated secretion of growth factors with enhanced cell proliferation and migration ability in response to electrical stimulation. An in vivo study in the Sprague Dawley rat model revealed a rapid wound closure within 7 days compared to 20 days of usual healing process in rodents.
Electrical stimulation (ES) via rigid electrodes near the wound is one of the promising approaches for chronic wound treatment, but it is unable to stimulate the whole wound area and treat infected wounds. In this study, a tough conductive hydrogel was prepared by the copolymerization of N-acryloyl glycinamide (NAGA) with quaternized chitosan-g-polyaniline (QCSP). The hydrogel showed a similar conductivity to the human skin and robust mechanical properties due to the dual hydrogen bonding motifs. The grafted polyaniline segments and functionalized quaternary ammonium groups showed intense antimicrobial activity against Pseudomonas aeruginosa and Staphylococcus aureus biofilms. The in vivo assay in diabetic rats proves that the ES via the conductive hydrogel was more effective in promoting the healing of infected wounds than the conventional ES via rigid electrodes. Due to the excellent flexibility and antibacterial properties, this conductive hydrogel shows great promise for infected chronic wound treatment.
Electricity constitutes a natural biophysical component that preserves tissue homeostasis and modulates many biological processes, including the repair of damaged tissues. Wound healing involves intricate cellular events, such as inflammation, angiogenesis, matrix synthesis, and epithelialization whereby multiple cell types sense the environmental cues to rebuild the structure and functions. Here, we report that electricity auto-generating glucose-responsive enzymatic-biofuel-cell (EBC) skin patch stimulates the wound healing process. Rat wounded-skin model and in vitro cell cultures showed that EBC accelerated wound healing by modulating inflammation while stimulating angiogenesis, fibroblast fuctionality and matrix synthesis. Of note, EBC-activated cellular bahaviors were linked to the signalings involved with calcium influx, which predominantly dependent on the mechanosensitive ion channels, primarily Piezo1. Inhibition of Piezo1-receptor impaired the EBC-induced key functions of both fibroblasts and endothelial cells in the wound healing. This study highlights the significant roles of electricity played in wound healing through activated mechanosensitive ion channels and the calcium influx, and suggests the possibility of the electricity auto-generating EBC-based skin patch for use as a wound healing device.
Biocompatible conductors are important components for soft and stretchable bioelectronics for digital healthcare, which have attracted extensive research efforts. Natural biopolymers, compared to other polymers, possess unique features that make them promising building blocks for biocompatible conductors, such as good biocompatibility/biodegradability, natural abundance, sustainability, and capability, can be processed into various functional formats with tunable material properties under benign conditions. In this comprehensive review, we focus on the recent advances in biocompatible conductors based on natural biopolymers for stretchable bioelectronics. We first give a brief introduction of conductive components and natural polymers and summarize the recent development of biocompatible conductors based on representative natural biopolymers including protein (silk), polypeptide (gelatin), and polysaccharide (alginate). The design and fabrication strategies for biocompatible conductors based on these representative biopolymers are outlined, after the chemical structure and properties of such biopolymers are presented. Then we discuss the electronic component-biopolymer interface and bioelectronic-biological tissue (skin and internal tissues) interface, highlight various fabrication techniques of biocompatible conductors for soft bioelectronics, and introduce representative examples of utilizing natural biopolymer-based biocompatible conductors for on-skin bioelectronics, textile-based wearable electronics, and implantable bioelectronics for digital healthcare. Finally, we present concluding remarks on challenges and prospects for designing natural biopolymers for soft biocompatible conductors and bioelectronics.
Recent advances in bioelectronics, such as skin-mounted electroencephalography sensors, multi-channel neural probes, and closed-loop deep brain stimulators, have enabled electrophysiological brain activities to be both monitored and modulated. Despite this remarkable progress, major challenges remain, which stem from the inherent mechanical, chemical, and electrical differences that exist between brain tissues and bioelectronics. New approaches are therefore required to address these mismatches between biotic and abiotic systems. Here, we review recent technological advances that minimize such mismatches by using unconventional soft materials, such as silicon/metal nanowires, functionalized hydrogels, and stretchable conductive nanocomposites, as well as customized fabrication processes and novel device designs. The resulting novel, soft bioelectronic devices provide new opportunities for brain research and clinical neuroengineering.
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, electroconductive hydrogel composed of polypyrrole-incorporated poly(vinyl alcohol) (PYP) hydrogels were used. PYP hydrogel facilitated electron transfer from the RED battery and facilitated the mobility of electrically mobile DNs release from 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 anti-obese 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 non-invasive way.
Conductive polymers are promising for bone regeneration because they can regulate cell behavior through electrical stimulation; moreover, they are antioxidative agents that can be used to protect cells and tissues from damage originating from reactive oxygen species (ROS). However, conductive polymers lack affinity to cells and osteoinductivity, which limits their application in tissue engineering. Herein, an electroactive, cell affinitive, persistent ROS‐scavenging, and osteoinductive porous Ti scaffold is prepared by the on‐surface in situ assembly of a polypyrrole‐polydopamine‐hydroxyapatite (PPy‐PDA‐HA) film through a layer‐by‐layer pulse electrodeposition (LBL‐PED) method. During LBL‐PED, the PPy‐PDA nanoparticles (NPs) and HA NPs are in situ synthesized and uniformly coated on a porous scaffold from inside to outside. PDA is entangled with and doped into PPy to enhance the ROS scavenging rate of the scaffold and realize repeatable, efficient ROS scavenging over a long period of time. HA and electrical stimulation synergistically promote osteogenic cell differentiation on PPy‐PDA‐HA films. Ultimately, the PPy‐PDA‐HA porous scaffold provides excellent bone regeneration through the synergistic effects of electroactivity, cell affinity, and antioxidative activity of the PPy‐PDA NPs and the osteoinductivity of HA NPs. This study provides a new strategy for functionalizing porous scaffolds that show great promise as implants for tissue regeneration.
ConspectusSoft bioelectronics intended for application to wearable and implantable biomedical devices have attracted great attention from material scientists, device engineers, and clinicians because of their extremely soft mechanical properties that match with a variety of human organs and tissues, including the brain, heart, skin, eye, muscles, and neurons, as well as their wide diversity in device designs and biomedical functions that can be finely tuned for each specific case of applications. These unique features of the soft bioelectronics have allowed minimal mechanical and biological damage to organs and tissues integrated with bioelectronic devices and reduced side effects including inflammation, skin irritation, and immune responses even after long-term biointegration. These favorable properties for biointegration have enabled long-term monitoring of key biomedical indicators with high signal-to-noise ratio, reliable diagnosis of the patient's health status, and in situ feedback therapy with high treatment efficacy optimized for the requirements of each specific disease model. These advantageous device functions and performances could be maximized by adopting novel high-quality soft nanomaterials, particularly ultrathin two-dimensional (2D) materials, for soft bioelectronics.Two-dimensional materials are emerging material candidates for the channels and electrodes in electronic devices (semiconductors and conductors, respectively). They can also be applied to various biosensors and therapeutic actuators in soft bioelectronics. The ultrathin vertically layered nanostructure, whose layer number can be controlled in the synthesis step, and the horizontally continuous planar molecular structure, which can be found over a large area, have conferred unique mechanical, electrical, and optical properties upon the 2D materials. The atomically thin nanostructure allows mechanical softness and flexibility and high optical transparency of the device, while the large-area continuous thin film structure allows efficient carrier transport within the 2D plane. In addition, the quantum confinement effect in the atomically thin 2D layers introduces interesting optoelectronic properties and superb photodetecting capabilities. When fabricated as soft bioelectronic devices, these interesting and useful material features of the 2D materials enable unconventional device functions in biological and optical sensing, as well as superb performance in electrical and biochemical therapeutic actuations.In this Account, we first summarize the distinctive characteristics of the 2D materials in terms of the mechanical, optical, chemical, electrical, and biomedical aspects and then present application examples of the 2D materials to soft bioelectronic devices based on each aforementioned unique material properties. Among various kinds of 2D materials, we particularly focus on graphene and MoS2. The advantageous material features of graphene and MoS2 include ultrathin thickness, facile functionalization, large surface-to-volume ratio, biocompatibility, superior photoabsorption, and high transparency, which allow the development of high-performance multifunctional soft bioelectronics, such as a wearable glucose patch, a highly sensitive humidity sensor, an ultrathin tactile sensor, a soft neural probe, a soft retinal prosthesis, a smart endoscope, and a cell culture platform. A brief comparison of their characteristics and performances is also provided. Finally, this Account concludes with a future outlook on next-generation soft bioelectronics based on 2D materials.
This review describes recent developments in the field of conductive nanomaterials and their application in 2D and 3D printed flexible electronics, with particular emphasis on inks based on metal nanoparticles and nanowires, carbon nanotubes, and graphene sheets. We present the basic properties of these nanomaterials, their stabilization in dispersions, formulation of conductive inks and formation of conductive patterns on flexible substrates (polymers, paper, textile) by using various printing technologies and post-printing processes. Applications of conductive nanomaterials for fabrication of various 2D and 3D electronic devices are also briefly discussed.
The increased need for wearable and implantable medical devices has driven the demand for electronics that interface with living systems. Current bioelectronic systems have not fully resolved mismatches between engineered circuits and biological systems, including the resulting pain and damage to biological tissues. Here, salt/poly(ethylene glycol) (PEG) aqueous two‐phase systems are utilized to generate programmable hydrogel ionic circuits. High‐conductivity salt‐solution patterns are stably encapsulated within PEG hydrogel matrices using salt/PEG phase separation, which route ionic current with high resolution and enable localized delivery of electrical stimulation. This strategy allows designer electronics that match biological systems, including transparency, stretchability, complete aqueous‐based connective interface, distribution of ionic electrical signals between engineered and biological systems, and avoidance of tissue damage from electrical stimulation. The potential of such systems is demonstrated by generating light‐emitting diode (LED)‐based displays, skin‐mounted electronics, and stimulators that deliver localized current to in vitro neuron cultures and muscles in vivo with reduced adverse effects. Such electronic platforms may form the basis of future biointegrated electronic systems. Programmable hydrogel ionic circuits completely composed of salt, water, and biofriendly hydrogels are developed based on salt/poly(ethylene glycol) aqueous two‐phase systems. Such systems enable designer electronics that match the properties of biological systems and route high‐resolution ionic electrical signals between engineered and living systems while avoiding tissue damage. Such platforms may form the basis of future biointegrated electronic systems.
Reducing the foreign body response (FBR) to implanted biomaterials will enhance their performance in tissue engineering. Poly(ethylene glycol) (PEG) hydrogels are increasingly popular for this application due to their low cost, ease of use, and the ability to tune their compliance via molecular weight and crosslinking densities. PEG hydrogels can elicit chronic inflammation in vivo, but recent evidence has suggested that extremely hydrophilic, zwitterionic materials and particles can evade the immune system. To combine the advantages of PEG-based hydrogels with the hydrophilicity of zwitterions, we synthesized hydrogels with co-monomers PEG and the zwitterion phosphorylcholine (PC). Recent evidence suggests that stiff hydrogels elicit increased immune cell adhesion to hydrogels, which we attempted to reduce by increasing hydrogel hydrophilicity. Surprisingly, hydrogels with the highest amount of zwitterionic co-monomer elicited the highest FBR we observed. Lowering the hydrogel modulus (165 kPa to 3 kPa), or PC content (20 wt% to 0 wt%), mitigated this effect. A high density of macrophages was found at the surface of implants associated with a high FBR, and mass spectrometry analysis of the proteins adsorbed to these gels implicated extracellular matrix, immune response, and cell adhesion protein categories as drivers of macrophage recruitment to these hydrogels. Overall, we show that modulus regulates macrophage adhesion to zwitterionic-PEG hydrogels, and demonstrate that chemical modifications to hydrogels should be studied in parallel with their physical properties to optimize implant design.
A new conceptual method termed as suspension 3D printing is demonstrated using self-healing hydrogel support to create macroscopic structures of liquid metal that exhibits properties indicative of a nonprintable object. The relationships between the process parameters, supporting gel concentration, and the deposited microdroplet geometry are clarified. The smaller nozzle inner diameter, lower flow rate, and higher printing speed will lead to a smaller droplets size. The gel concentration plays a significant role on patterning the droplets space. The results presented can be applied to design the target feature and further optimize the input parameters. Besides, this paper also illustrates the capability and potential application of the method in constructing 3D macrostructures and stereo electronic systems using these liquid metal droplets. Based on this strategy, it is possible to print liquid metal into sophisticated multidimensional and shape transformable functional structures ignoring the effects of fluid instability, gravity, and surface tension. Furthermore, this work can help remove the limits of materials and technical barriers to enable a wide variety of materials to be printed into arbitrary shapes. It is expected that further practices of the methodology will facilitate the advancements in multiscale droplets generation, flexible electronics, encapsulation technologies, biology and medicine, etc.
Plastic bioelectronics is a research field that takes advantage of the inherent properties of polymers and soft organic electronics for applications at the interface of biology and electronics. The resulting electronic materials and devices are soft, stretchable and mechanically conformable, which are important qualities for interacting with biological systems in both wearable and implantable devices. Work is currently aimed at improving these devices with a view to making the electronic–biological interface as seamless as possible.
The dynamic behavior of porcine brain tissue, obtained from a series of in vitro observations and experiments, is analyzed and described here with the aid of a large strain, nonlinear, viscoelastic constitutive model. Mixed gray and white matter samples excised from the superior cortex were tested in unconfined uniaxial compression within 15h post mortem. The test sequence consisted of three successive load-unload segments at strain rates of 1, 0.1 and 0.01 s⁻¹, followed by stress relaxation (n=25). The volumetric compliance of the tissue was assessed for a subset of specimens (n=7) using video extensometry techniques. The tissue response exhibited moderate compressibility, substantial nonlinearity, hysteresis, conditioning and rate dependence. A large strain kinematics nonlinear viscoelastic model was developed to account for the essential features of the tissue response over the entire deformation history. The corresponding material parameters were obtained by fitting the model to the measured conditioned response (axial and volumetric) via a numerical optimization scheme. The model successfully captures the observed complexities of the material response in loading, unloading and relaxation over the entire range of strain rates. The accuracy of the model was further verified by comparing model predictions with the tissue response in unconfined compression at higher strain rate (10 s⁻¹) and with literature data in uniaxial tension. The proposed constitutive framework was also found to be adequate to model the loading response of brain tissue in uniaxial compression over a wider range of strain rates (0.01-3000 s⁻¹), thereby providing a valuable tool for simulations of dynamic transients (impact, blast/shock wave propagation) leading to traumatic brain injury.
The effect of differentiation on the transverse mechanical properties of mammalian myocytes was determined by using atomic force microscopy. The apparent elastic modulus increased from 11.5 +/- 1.3 kPa for undifferentiated myoblasts to 45.3 +/- 4.0 kPa after 8 days of differentiation (P < 0.05). The relative contribution of viscosity, as determined from the normalized hysteresis area, ranged from 0.13 +/- 0.02 to 0.21 +/- 0.03 and did not change throughout differentiation. Myosin expression correlated with the apparent elastic modulus, but neither myosin nor beta-tubulin were associated with hysteresis. Microtubules did not affect mechanical properties because treatment with colchicine did not alter the apparent elastic modulus or hysteresis. Treatment with cytochalasin D or 2,3-butanedione 2-monoxime led to a significant reduction in the apparent elastic modulus but no change in hysteresis. In summary, skeletal muscle cells exhibited viscoelastic behavior that changed during differentiation, yielding an increase in the transverse elastic modulus. Major contributors to changes in the transverse elastic modulus during differentiation were actin and myosin.
This paper presents results from a finite element study of the biomechanics of hydrocephalus, with special emphasis on a reassessment of the parenchyma elastic modulus. A two-dimensional finite element model of the human brain/ventricular system is developed and analysed under hydrocephalic loading conditions. It is shown that the Young's modulus of the brain parenchyma used in previous studies (3000-10000 Pa) corresponds to strain rates much higher than those present in hydrocephalic brains. Consideration of the brain's viscoelasticity leads to the derivation of a considerably lower modulus value of approximately 584 Pa.
Brain tissue mechanical properties have been well-characterized in vitro, and were found to be inhomogeneous, nonlinear anisotropic and influenced by neurological development and postmortem time interval prior to testing. However, brain in vivo is a vascularized tissue, and there is a paucity of information regarding the effect of perfusion on brain mechanical properties. Furthermore, mechanical properties are often extracted from preconditioned tissue, and it remains unclear if these properties are representative of non-preconditioned tissue. We present non-preconditioned (NPC) and preconditioned (PC) relaxation responses of porcine brain (N = 10) obtained in vivo, in situ and in vitro, at anterior, mid and posterior regions of the cerebral cortex during 4mm indentations at either 3 or 1 mm/s. Material property characteristics showed no dependency on the site tested, thus revealing that cortical gray matter on the parietal and frontal lobes can be considered homogenous. In most cases, preconditioning decreased the shear moduli, with a more pronounced effect in the dead (in situ and in vitro) brain. For most conditions, it was found that only the long-term time constant of relaxation (tau > 20 s) significantly decreased from in vivo to in situ modes (p < 0.02), and perfusion had no effect on any other property. These findings support the concept that perfusion does not affect the stiffness of living cortical tissue.
For pt.VII see J. Neurosci. Methods, vol.9, p.301-8 (1983). The charge injection limits of a Pt electrode using 0.2 ms charge balanced, biphasic current pulses range from 50 to 150 mu C/cm 2 geometric if the potential excursions of the electrode are kept below those at which H 2 or O 2 are produced. These charge densities are three to ten times smaller than the currently accepted value based on earlier experiments in which the reversible surface reactions were fully utilized and the pulse widths were longer. Several qualifying comments are made regarding the experimental results.