As a new class of materials, implantable flexible electrical conductors have recently been developed and applied to bioelectronics. An ideal electrical conductor requires high conductivity, ...tissue‐like mechanical properties, low toxicity, reliable adhesion to biological tissues, and the ability to maintain its shape in wet physiological environments. Despite significant advances, electrical conductors that satisfy all these requirements are insufficient. Herein, a facile method for manufacturing a new conductive hydrogels through the simultaneous exfoliation of graphite and polymerization of zwitterionic monomers triggered by microwave irradiation is introduced. The mechanical properties of the obtained conductive hydrogel are similar to those of living tissue, which is ideal as a bionic adhesive for minimizing contact damage due to mechanical mismatches between hard electronics and soft tissues. Furthermore, it exhibits excellent adhesion performance, electrical conductivity, non‐swelling, and high conformability in water. Excellent biocompatibility of the hydrogel is confirmed through a cytotoxicity test using C2C12 cells, a biocompatibility test on rat tissues, and their histological analysis. The hydrogel is then implanted into the sciatic nerve of a rat and neuromodulation is demonstrated through low‐current electrical stimulation. This hydrogel demonstrates a tissue‐like extraneuronal electrode, which possesses high conformability to improve the tissue–electronics interfaces, promising next‐generation bioelectronics applications.
A new conductive hydrogel is developed through the simultaneous exfoliation of graphite and polymerization of zwitterionic monomers triggered by microwave irradiation. This hydrogel demonstrates tissue‐like extraneuronal electrodes satisfying requirements of bioelectronics such as low storage modulus, high viscoelasticity, low toxicity, reliable adhesion, and conformability to biological tissues, and maintenance of conductivity and hydrogel volume in wet environments.
Recent studies on soft adhesives have sought to deeply understand how their chemical or mechanical structures interact strongly with living tissues. The aim is to optimally address the unmet needs of ...patients with acute or chronic diseases. Synergistic adhesion involving both electrostatic (hydrogen bonds) and mechanical interactions (capillarity‐assisted suction stress) seems to be effective in overcoming the challenges associated with long‐term unstable coupling to tissues. Here, an electrostatically and mechanically synergistic mechanism of residue‐free, sustainable, in situ tissue adhesion by implementing hybrid multiscale architectonics. To deduce the mechanism, a thermodynamic model based on a tailored multiscale combinatory adhesive is proposed. The model supports the experimental results that the thermodynamically controlled swelling of the nanoporous hydrogel embedded in the hierarchical elastomeric structure enhances biofluid‐insensitive, sustainable, in situ adhesion to diverse soft, slippery, and wet organ surfaces, as well as clean detachment in the peeling direction. Based on the robust tissue adhesion capability, universal reliable measurements of electrophysiological signals generated by various tissues, ranging from rodent sciatic nerve, the muscle, brain, and human skin, are successfully demonstrated.
Electrostatic–mechanical, synergistic, in situ, multiscale tissue adhesion for various bioelectronic applications is demonstrated. To deduce the mechanism, a thermodynamic model based on a tailored elastomer–hydrogel combinatory adhesive architecture is proposed. Reliable real‐time measurements of electrophysiological signals generated by various tissues, ranging from rodent sciatic nerve, the muscle, brain, and human skin, are also successfully demonstrated.
Customizable bioadhesives for individual organ requirements, including tissue type and motion, are essential, especially given the rise in implantable medical device applications demanding adequate ...underwater adhesion. While synthetic bioadhesives are widely used, their toxicity upon degradation shifts focus to biocompatible natural biomaterials. However, enhancing the adhesive strengths of these biomaterials presents ongoing challenges while accommodating the unique properties of specific organs. To address these issues, three types of customized underwater bioadhesive patches (CUBAPs) with strong, water‐responsive adhesion and controllable biodegradability and stretchability based on bioengineered mussel adhesive proteins conjugated with acrylic acid and/or methacrylic acid are proposed. The CUBAP system, although initially nonadhesive, shows strong underwater adhesion upon hydration, adjustable biodegradation, and adequate physical properties by adjusting the ratio of poly(acrylic acid) and poly(methacrylic acid). Through ex vivo and in vivo evaluations using defective organs and the implantation of electronic devices, the suitability of using CUBAPs for effective wound healing in diverse internal organs is demonstrated. Thus, this innovative CUBAP system offers strong underwater adhesiveness with tailored biodegradation timing and physical properties, giving it great potential in various biomedical applications.
This paper proposes a unique bioadhesive patch, CUBAP, which is a crosslinked mussel protein with UV‐induced polyacrylation designed to adhere underwater for various biomedical applications. CUBAP is nontoxic and customizable, providing strong water‐responsive adhesion, adjustable biodegradability, and controllable physical properties suitable for healing wounds in specific internal organs and for the implantation of electronic medical devices.
Abstract
Realizing a clinical-grade electronic medicine for peripheral nerve disorders is challenging owing to the lack of rational material design that mimics the dynamic mechanical nature of ...peripheral nerves. Electronic medicine should be soft and stretchable, to feasibly allow autonomous mechanical nerve adaptation. Herein, we report a new type of neural interface platform, an adaptive self-healing electronic epineurium (A-SEE), which can form compressive stress-free and strain-insensitive electronics-nerve interfaces and enable facile biofluid-resistant self-locking owing to dynamic stress relaxation and water-proof self-bonding properties of intrinsically stretchable and self-healable insulating/conducting materials, respectively. Specifically, the A-SEE does not need to be sutured or glued when implanted, thereby significantly reducing complexity and the operation time of microneurosurgery. In addition, the autonomous mechanical adaptability of the A-SEE to peripheral nerves can significantly reduce the mechanical mismatch at electronics-nerve interfaces, which minimizes nerve compression-induced immune responses and device failure. Though a small amount of Ag leaked from the A-SEE is observed in vivo (17.03 ppm after 32 weeks of implantation), we successfully achieved a bidirectional neural signal recording and stimulation in a rat sciatic nerve model for 14 weeks. In view of our materials strategy and in vivo feasibility, the mechanically adaptive self-healing neural interface would be considered a new implantable platform for a wide range application of electronic medicine for neurological disorders in the human nervous system.
Soft neuroprosthetics that monitor signals from sensory neurons and deliver motor information can potentially replace damaged nerves. However, achieving long‐term stability of devices interfacing ...peripheral nerves is challenging, since dynamic mechanical deformations in peripheral nerves cause material degradation in devices. Here, a durable and fatigue‐resistant soft neuroprosthetic device is reported for bidirectional signaling on peripheral nerves. The neuroprosthetic device is made of a nanocomposite of gold nanoshell (AuNS)‐coated silver (Ag) flakes dispersed in a tough, stretchable, and self‐healing polymer (SHP). The dynamic self‐healing property of the nanocomposite allows the percolation network of AuNS‐coated flakes to rebuild after degradation. Therefore, its degraded electrical and mechanical performance by repetitive, irregular, and intense deformations at the device–nerve interface can be spontaneously self‐recovered. When the device is implanted on a rat sciatic nerve, stable bidirectional signaling is obtained for over 5 weeks. Neural signals collected from a live walking rat using these neuroprosthetics are analyzed by a deep neural network to predict the joint position precisely. This result demonstrates that durable soft neuroprosthetics can facilitate collection and analysis of large‐sized in vivo data for solving challenges in neurological disorders.
A soft but durable fatigue‐resistant neuroprosthetic device is proposed for peripheral nerve interfacing based on a self‐recoverable nanocomposite. The nanocomposite can spontaneously recover its electrical conductivity even after repetitive degradations by severe mechanical deformation. The neuroprosthetics implanted on a rat sciatic nerve achieve stable bidirectional signaling for 5 weeks. Deep neural network analysis predicts the joint position of the rat precisely.
Cuff electrodes have been introduced into functional neuromuscular stimulation systems to either obtain neural signals or elicit limb movements. Multiple electrodes must be implanted to construct a ...feedback control loop, including one electrode for acquisition and another for stimulation. Existing approaches require too much space inside the body and a complicated surgical procedure. This paper proposes a novel neural interface method that uses a single cuff electrode with multichannel capability to simultaneously acquire multichannel recordings and induce electrical stimulation at the proximal nerve trunk of the sciatic nerve. Recordings and stimulation are conducted in a time-shared manner using a path controller. Using the proposed method, joint positions are estimated from multichannel recorded neural signals during electrical stimulation as neural signals are continuously recorded. In addition, the proposed system is shown to be suitable for controlling joint position. The proposed neural interface method overcomes the spatial limitations of electrode implantation and thus offers a new approach to developing compact neural interface systems.
Addressing peripheral nerve disorders with electronic medicine poses significant challenges, especially in replicating the dynamic mechanical properties of nerves and understanding their ...functionality. In the field of electronic medicine, it is crucial to design a system that thoroughly understands the functions of the nervous system and ensures a stable interface with nervous tissue, facilitating autonomous neural adaptation. Herein, we present a novel neural interface platform that modulates the peripheral nervous system using flexible nerve electrodes and advanced neuromodulation techniques. Specifically, we have developed a surface-based inverse recruitment model for effective joint position control via direct electrical nerve stimulation. Utilizing barycentric coordinates, this model constructs a three-dimensional framework that accurately interpolates inverse isometric recruitment values across various joint positions, thereby enhancing control stability during stimulation. Experimental results from rabbit ankle joint control trials demonstrate our model's effectiveness. In combination with a proportional-integral-derivative (PID) controller, it shows superior performance by achieving reduced settling time (less than 1.63 s), faster rising time (less than 0.39 s), and smaller steady-state error (less than 3 degrees) compared to the legacy model. Moreover, the model's compatibility with recent advances in flexible interfacing technologies and its integration into a closed-loop controlled functional neuromuscular stimulation (FNS) system highlight its potential for precise neuroprosthetic applications in joint position control. This approach marks a significant advancement in the management of neurological disorders with advanced neuroprosthetic solutions.
Optogenetic stimulation of the peripheral nervous system is a novel approach to motor control, somatosensory transduction, and pain processing. Various optical stimulation tools have been developed ...for optogenetic stimulation using optical fibers and light-emitting diodes positioned on the peripheral nerve. However, these tools require additional sensors to monitor the limb or muscle status. We present herein a novel optical nerve cuff electrode that uses a single cuff electrode to conduct to simultaneously monitor neural activity and optogenetic stimulation of the peripheral nerve. The proposed optical nerve cuff electrode is designed with a polydimethylsiloxane substrate, on which electrodes can be positioned to record neural activity. We confirm that the illumination intensity and the electrical properties of the optical nerve cuff electrode are suitable for optical stimulation with simultaneous neural activity monitoring in Thy1::ChR2 transgenic mice. With the proposed electrode, the limb status is monitored with continuous streaming signals during the optical stimulation of anesthetized and moving animals. In conclusion, this optical nerve cuff electrode provides a new optical modulation tool for peripheral nervous system studies.
Cuff electrode recording has been proposed as a solution to obtain robust feedback signals for closed-loop controlled functional neuromuscular stimulation (FNS) systems. However, single-channel cuff ...electrode recording requires several electrodes to obtain the feedback signal related to each muscle. In this study, we propose an ankle-angle estimation method in which recording is conducted from the proximal nerve trunk with a multichannel cuff electrode to minimize cuff electrode usage. In experiments, muscle afferent signals were recorded from a rabbit's proximal sciatic nerve trunk using a multichannel cuff electrode, and blind source separation and ankle-angle estimation were performed using fast independent component analysis (PP/FastICA) combined with dynamically driven recurrent neural network (DDRNN). The experimental results indicate that the proposed method has high ankle-angle estimation accuracy for both situations when the ankle motion is generated by position servo system or neuromuscular stimulation. Furthermore, the results confirm that the proposed method is applicable to closed-loop FNS systems to control limb motion.
•TH-positive cell loss in the SNc was observed in accordance with 6-OHDA treatment.•Mice treated with higher 6-OHDA concentrations exhibited degenerated motor symptoms.•STN neuronal firing rates ...showed comparable results to those of human PD.•The mouse model mimics the unique characteristics of each progressive stage of human PD.
Parkinson's disease (PD) is characterized by abnormal motor symptoms and increased neuronal activity in the subthalamic nucleus (STN) as the disease progresses. We investigated the behavioral and electrophysiological characteristics in a mouse model mimicking the progressive stages of human PD (early, moderate, and advanced) by injecting 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle (MFB) at three different concentrations (2, 4, and 6μg/2μl). Significant changes in motor symptoms were demonstrated between groups in association with relative TH-positive cell loss in the substantia nigra pars compacta (SNc). Moreover, electrophysiologically assessed changes in the mean neuronal firing rate in the STN neurons were comparable to those in the early to advanced stages of human PD. Thus, the mouse model presented herein replicates the unique characteristics of each progressive stage of PD, in both motor and neurophysiological aspects, and therefore can be useful for further investigations of PD pathology.
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