Chronic Neural Interface Research Articles

Robust Neural Interfaces with Photopatternable, Bioadhesive, and Highly Conductive Hydrogels for Stable Chronic Neuromodulation.

A robust neural interface with intimate electrical coupling between neural electrodes and neural tissues is critical for stable chronic neuromodulation. The development of bioadhesive hydrogel neural electrodes is a potential approach for tightly fixing the neural electrodes on the epineurium surface to construct a robust neural interface. Herein, we construct a photopatternable, antifouling, conductive (∼6 S cm-1), bioadhesive (interfacial toughness ∼100 J m-2), soft, and elastic (∼290% strain, Young's modulus of 7.25 kPa) hydrogel to establish a robust neural interface for bioelectronics. The UV-sensitive zwitterionic monomer can facilitate the formation of an electrostatic-assembled conductive polymer PEDOT:PSS network, and it can be further photo-cross-linked into elastic polymer network. Such a semi-interpenetrating network endows the hydrogel electrodes with good conductivity. Especially, the photopatternable feature enables the facile microfabrication processes of multifunctional hydrogel (MH) interface with a characteristic size of 50 μm. The MH neural electrodes, which show improved performance of impedance, charge storage capacity, and charge injection capability, can produce effective electrical stimulation with high current density (1 mA cm-2) at ultralow voltages (±25 mV). The MH interface could realize high-efficient electrical communication at the chronic neural interface for stable recording and stimulation of a sciatic nerve in the rat model.

Injectable and tissue-conformable conductive hydrogel for MRI-compatible brain-interfacing electrodes

The development of flexible and stretchable materials has led to advances in implantable bio-integrated electronic devices that can sense physiological signals or deliver electrical stimulation to various organs in the human body. Such devices are particularly useful for neural interfacing systems that monitor neurodegenerative diseases such as Parkinson’s disease or epilepsy in real time. However, coupling current brain-interfacing devices with magnetic resonance imaging (MRI) remains a practical challenge due to resonance frequency variations from inorganic metal-based devices. Thus, organic conductive materials, such as poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS), have recently been considered as promising candidates. Nonetheless, their conformability on curvilinear tissues remains questionable. In this study, we developed an injectable conductive hydrogel (ICH) composed of tyramine-conjugated hyaluronic acid (HATYR) and PEDOT:PSS for MRI-compatible brain-interfacing electrodes. Our ICH produced low impedance around 5 kΩ even under 10 Hz, demonstrating high confidence volumetric capacitance. Due to HATYR’s biocompatibility, histological and cytotoxicity assays showed almost no inflammation and toxicity, respectively; in addition, ICH was able to degrade into 40% of its original volume within four weeks in vivo. An electrocorticogram (ECoG) array was also patternable by syringe injections of ICH on a stretchable and flexible elastomeric substrate layer that conformed to curvy brain tissues and successfully recorded ECoG signals under light stimulation. Furthermore, MRI imaging of implanted devices did not show any artifacts, indicating the potential of the MRI-compatible hydrogel electrodes for advanced ECoG arrays. This study provides a promising solution for MRI-compatible neural electrodes, enabling the advancement of chronic neural interfacing systems for monitoring neurodegenerative diseases.

Slippery Epidural ECoG Electrode for High-Performance Neural Recording and Interface.

Chronic implantation of an epidural Electrocorticography (ECoG) electrode produces thickening of the dura mater and proliferation of the fibrosis around the interface sites, which is a significant concern for chronic neural ECoG recording applications used to monitor various neurodegenerative diseases. This study describes a new approach to developing a slippery liquid-infused porous surface (SLIPS) on the flexible ECoG electrode for a chronic neural interface with the advantage of increased cell adhesion. In the demonstration, the electrode was fabricated on the polyimide (PI) substrate, and platinum (Pt)-gray was used for creating the porous nanocone structure for infusing the silicone oil. The combination of nanocone and the infused slippery oil layer created the SLIPS coating, which has a low impedance (4.68 kΩ) level favourable for neural recording applications. The electrochemical impedance spectroscopy and equivalent circuit modelling also showed the effect of the coating on the recording site. The cytotoxicity study demonstrated that the coating does not have any cytotoxic potentiality; hence, it is biocompatible for human implantation. The in vivo (acute recording) neural recording on the rat model also confirmed that the noise level could be reduced significantly (nearly 50%) and is helpful for chronic ECoG recording for more extended neural signal recording applications.

Harnessing the 2D Structure-Enabled Viscoelasticity of Graphene-Based Hydrogel Membranes for Chronic Neural Interfacing.

Stiffness and viscoelasticity of neural implants regulate the foreign body response. Recent studies have suggested the use of elastic or viscoelastic materials with tissue-like stiffness for long-term neural electrical interfacing. Herein, the authors find that a viscoelastic multilayered graphene hydrogel (MGH) membrane, despite exhibiting a much higher Young's modulus than nerve tissues, shows little inflammatory response after 8-week implantation in rat sciatic nerves. The MGH membrane shows significant viscoelasticity due to the slippage between graphene nanosheets, facilitating its seamless yet minimally compressive interfacing with nerves to reduce the inflammation caused by the stiffness mismatch. When used as neural stimulation electrodes, the MGH membrane can offer abundant ion-accessible surfaces to bring a charge injection capacity 1-2 orders of magnitude higher than its traditional Pt counterpart, and further demonstrates chronic neural therapy potential in low-voltage modulation of rat blood pressure. This work suggests that the emergence of 2D nanomaterials and particularly their unique structural attributes can be harnessed to enable new bio-interfacing design strategies.

The development of microfabricated solenoids with magnetic cores for micromagnetic neural stimulation

Electrical stimulation via invasive microelectrodes is commonly used to treat a wide range of neurological and psychiatric conditions. Despite its remarkable success, the stimulation performance is not sustainable since the electrodes become encapsulated by gliosis due to foreign body reactions. Magnetic stimulation overcomes these limitations by eliminating the need for a metal-electrode contact. Here, we demonstrate a novel microfabricated solenoid inductor (80 µm × 40 µm) with a magnetic core that can activate neuronal tissue. The characterization and proof-of-concept of the device raise the possibility that micromagnetic stimulation solenoids that are small enough to be implanted within the brain may prove to be an effective alternative to existing electrode-based stimulation devices for chronic neural interfacing applications.

(Invited) Soft Wireless Optofluidic and Optoelectronic Implants for Advanced Chronic Neural Interfacing

Optogenetics and neuropharmacology holds immense promise for dissection of neural circuits and cellular signaling in freely behaving animals. However, the full potential of their in vivo applications is limited by the use of conventional tools such as cannulas for drug delivery and fiber optics for photostimulation. These traditional approaches greatly damage neural tissue near the implant, hinder integration with different modalities, and severely limit the animal’s natural behavior and movement, mainly due to their rigid construction, bulky design, and tethered operation, respectively. Furthermore, current methods lack spatiotemporal control of drug delivery, wireless control, and multi-functionality.To address these fundamental limitations in in vivo neuroscience, we have developed soft wireless optofluidic and optoelectronic implants, which can provide wireless delivery of light and/or drugs in awake, moving animals. The devices consist of ultrathin and flexible probes, which integrate microscale inorganic light-emitting diodes and/or microfluidic channels, and wireless interface with an independent power supply. This design enables compact, lightweight and soft system, thus enabling seamless implantation and operation in the brain without causing disturbance of naturalistic behavior. With integration of smartphone control, replaceable drug cartridges for long-term drug delivery, and wireless energy harvesters for intervention-free charging, they can further facilitate chronic neural interfacing to uncover the basis for brain functions and neuropsychiatric diseases. We have successfully demonstrated chronic wireless capabilities of these devices in freely moving animals that can repeatedly deliver multiple wavelengths of light and drugs for long periods of time to manipulate animals’ behavior. The unique capabilities of the soft wireless implants forecasts their broad utility in chronic in vivo neuropharmacology and optogenetics for various neuroscience research and clinical applications.

Chronic neural activity recorded within breast tumors

Nerve fibers are known to reside within malignant tumors and the greater the neuronal density the worse prognosis for the patient. Recent discoveries using tumor bearing animal models have eluded to the autonomic nervous system having a direct effect on tumor growth and metastasis. We report the first direct and chronic in vivo measurements of neural activity within tumors. Using a triple-negative mammary cancer mouse model and chronic neural interface techniques, we have recorded neural activity directly within the tumor mass while the tumor grows and metastasizes. The results indicate that there is a strong connection between the autonomic nervous system and the tumor and could help uncover the mechanisms of tumor growth and metastasis.

Optimizing the neuron-electrode interface for chronic bioelectronic interfacing.

Engineering approaches have vast potential to improve the treatment of disease. Brain-machine interfaces have become a well-established means of treating some otherwise medically refractory neurological diseases, and they have shown promise in many more areas. More widespread use of implanted stimulating and recording electrodes for long-term intervention is, however, limited by the difficulty in maintaining a stable interface between implanted electrodes and the local tissue for reliable recording and stimulation.This loss of performance at the neuron-electrode interface is due to a combination of inflammation and glial scar formation in response to the implanted material, as well as electrical factors contributing to a reduction in function over time. An increasing understanding of the factors at play at the neural interface has led to greater focus on the optimization of this neuron-electrode interface in order to maintain long-term implant viability.A wide variety of approaches to improving device interfacing have emerged, targeting the mechanical, electrical, and biological interactions between implanted electrodes and the neural tissue. These approaches are aimed at reducing the initial trauma and long-term tissue reaction through device coatings, optimization of mechanical characteristics for maximal biocompatibility, and implantation techniques. Improved electrode features, optimized stimulation parameters, and novel electrode materials further aim to stabilize the electrical interface, while the integration of biological interventions to reduce inflammation and improve tissue integration has also shown promise.Optimization of the neuron-electrode interface allows the use of long-term, high-resolution stimulation and recording, opening the door to responsive closed-loop systems with highly selective modulation. These new approaches and technologies offer a broad range of options for neural interfacing, representing the possibility of developing specific implant technologies tailor-made to a given task, allowing truly personalized, optimized implant technology for chronic neural interfacing.

Chronic neural interfacing with cerebral cortex using single-walled carbon nanotube-polymer grids

Objective. The development of electrode arrays able to reliably record brain electrical activity is a critical issue in brain machine interface (BMI) technology. In the present study we undertook a comprehensive physico-chemical, physiological, histological and immunohistochemical characterization of new single-walled carbon nanotubes (SWCNT)-based electrode arrays grafted onto medium-density polyethylene (MD-PE) films. Approach. The long-term electrical stability, flexibility, and biocompatibility of the SWCNT arrays were investigated in vivo in laboratory rats by two-months recording and analysis of subdural electrocorticogram (ECoG). Ex-vivo characterization of a thin flexible and single probe SWCNT/polymer electrode is also provided. Main results. The SWCNT arrays were able to capture high quality and very stable ECoG signals across 8 weeks. The histological and immunohistochemical analyses demonstrated that SWCNT arrays show promising biocompatibility properties and may be used in chronic conditions. The SWCNT-based arrays are flexible and stretchable, providing low electrode-tissue impedance, and, therefore, high compliance with the irregular topography of the cortical surface. Finally, reliable evoked synaptic local field potentials in rat brain slices were recorded using a special SWCNT-polymer-based flexible electrode. Significance. The results demonstrate that the SWCNT arrays grafted in MD-PE are suitable for manufacturing flexible devices for subdural ECoG recording and might represent promising candidates for long-term neural implants for epilepsy monitoring or neuroprosthetic BMI.

Supramolecular Peptide Hydrogel-Based Soft Neural Interface Augments Brain Signals through a Three-Dimensional Electrical Network

Recording neural activity from the living brain is of great interest in neuroscience for interpreting cognitive processing or neurological disorders. Despite recent advances in neural technologies, development of a soft neural interface that integrates with neural tissues, increases recording sensitivity, and prevents signal dissipation still remains a major challenge. Here, we introduce a biocompatible, conductive, and biostable neural interface, a supramolecular β-peptide-based hydrogel that allows signal amplification via tight neural/hydrogel contact without neuroinflammation. The non-biodegradable β-peptide forms a multihierarchical structure with conductive nanomaterial, creating a three-dimensional electrical network, which can augment brain signal efficiently. By achieving seamless integration in brain tissue with increased contact area and tight neural tissue coupling, the epidural and intracortical neural signals recorded with the hydrogel were augmented, especially in the high frequency range. Overall, our tissuelike chronic neural interface will facilitate a deeper understanding of brain oscillation in broad brain states and further lead to more efficient brain-computer interfaces.

Methodology for creating a chronic osseointegrated neural interface for prosthetic control in rabbits

BackgroundChronic stability and high degrees of selectivity are both essential but somewhat juxtaposed components for creating an implantable bi-directional PNI capable of controlling of a prosthetic limb. While the more invasive implantable electrode arrays provide greater specificity, they are less stable over time due to compliance mismatch with the dynamic soft tissue environment in which the interface is created. New MethodThis paper takes the surgical approach of transposing nerves into bone to create neural interface within the medullary canal of long bones, an osseointegrated neural interface, to provide greater stability for implantable electrodes. In this context, we describe the surgical model for transfemoral amputation with transposition of the sciatic nerve into the medullary canal in rabbits. We investigate the capacity to create a neural interface within the medullary canal histolomorphologically. In a separate proof of concept experiment, we quantify the chronic physiological capacity of transposed nerves to conduct compound nerve action potentials evoked via an Osseointegrated Neural Interface. Comparison with Existing Method(s)The rabbit serves as an important animal model for both amputation neuroma and osseointegration research, but is underutilized for the exploration neural interfacing in an amputation setting. ResultsOur findings demonstrate that transposed nerves remain stable over 12 weeks. Creating a neural interface within the medullary canal is possible and does not impede nerve regeneration or physiological capacity. ConclusionsThis article represents the first evidence that an Osseointegrated Neural Interface can be surgically created, capable of chronic stimulation/recording from amputated nerves required for future prosthetic control.

Diamond/Porous Titanium Nitride Electrodes With Superior Electrochemical Performance for Neural Interfacing.

Robust devices for chronic neural stimulation demand electrode materials which exhibit high charge injection (Qinj) capacity and long-term stability. Boron-doped diamond (BDD) electrodes have shown promise for neural stimulation applications, but their practical applications remain limited due to the poor charge transfer capability of diamond. In this work, we present an attractive approach to produce BDD electrodes with exceptionally high surface area using porous titanium nitride (TiN) as interlayer template. The TiN deposition parameters were systematically varied to fabricate a range of porous electrodes, which were subsequently coated by a BDD thin-film. The electrodes were investigated by surface analysis methods and electrochemical techniques before and after BDD deposition. Cyclic voltammetry (CV) measurements showed a wide potential window in saline solution (between −1.3 and 1.2 V vs. Ag/AgCl). Electrodes with the highest thickness and porosity exhibited the lowest impedance magnitude and a charge storage capacity (CSC) of 253 mC/cm2, which largely exceeds the values previously reported for porous BDD electrodes. Electrodes with relatively thinner and less porous coatings displayed the highest pulsing capacitances (Cpulse), which would be more favorable for stimulation applications. Although BDD/TiN electrodes displayed a higher impedance magnitude and a lower Cpulse as compared to the bare TiN electrodes, the wider potential window likely allows for higher Qinj without reaching unsafe potentials. The remarkable reduction in the impedance and improvement in the charge transfer capacity, together with the known properties of BDD films, makes this type of coating as an ideal candidate for development of reliable devices for chronic neural interfacing.

Neural Interfaces Based on Amorphous Silicon Carbide Ultramicroelectrode Arrays

Size and material considerations are important in the development of next-generation chronically reliable neural interface devices. In this review, we discuss the use of amorphous silicon carbide (a-SiC) for the fabrication of indwelling electrode arrays with ultrathin penetrating shanks for neural stimulation and recording. The a-SiC film is stable in saline environments and has a high intrinsic stiffness that allows fabrication of tissue-penetrating arrays with extremely small cross-sectional areas (<60 μm2). Present literature on arrays with extremely small shanks and/or ultramicroelectrode (UME) sites are reviewed. Properties of a-SiC films and their current biomedical applications are summarized. Reduced shank dimensions increase the flexibility of high Young's modulus a-SiC arrays. Iridium oxide-coated UMEs had electrochemical properties suitable for neural recording and stimulation, and recorded neural signals with high amplitudes and high signal-to-noise ratios. UMEs and a-SiC may provide a platform for next-generation high-density chronic neural interface devices.

The History and Horizons of Microscale Neural Interfaces.

Microscale neural technologies interface with the nervous system to record and stimulate brain tissue with high spatial and temporal resolution. These devices are being developed to understand the mechanisms that govern brain function, plasticity and cognitive learning, treat neurological diseases, or monitor and restore functions over the lifetime of the patient. Despite decades of use in basic research over days to months, and the growing prevalence of neuromodulation therapies, in many cases the lack of knowledge regarding the fundamental mechanisms driving activation has dramatically limited our ability to interpret data or fine-tune design parameters to improve long-term performance. While advances in materials, microfabrication techniques, packaging, and understanding of the nervous system has enabled tremendous innovation in the field of neural engineering, many challenges and opportunities remain at the frontiers of the neural interface in terms of both neurobiology and engineering. In this short-communication, we explore critical needs in the neural engineering field to overcome these challenges. Disentangling the complexities involved in the chronic neural interface problem requires simultaneous proficiency in multiple scientific and engineering disciplines. The critical component of advancing neural interface knowledge is to prepare the next wave of investigators who have simultaneous multi-disciplinary proficiencies with a diverse set of perspectives necessary to solve the chronic neural interface challenge.

Chronic interfacing with the autonomic nervous system using carbon nanotube (CNT) yarn electrodes

The ability to reliably and safely communicate chronically with small diameter (100–300 µm) autonomic nerves could have a significant impact in fundamental biomedical research and clinical applications. However, this ability has remained elusive with existing neural interface technologies. Here we show a new chronic nerve interface using highly flexible materials with axon-like dimensions. The interface was implemented with carbon nanotube (CNT) yarn electrodes to chronically record neural activity from two separate autonomic nerves: the glossopharyngeal and vagus nerves. The recorded neural signals maintain a high signal-to-noise ratio (>10 dB) in chronic implant models. We further demonstrate the ability to process the neural activity to detect hypoxic and gastric extension events from the glossopharyngeal and vagus nerves, respectively. These results establish a novel, chronic platform neural interfacing technique with the autonomic nervous system and demonstrate the possibility of regulating internal organ function, leading to new bioelectronic therapies and patient health monitoring.

Methodological considerations for a chronic neural interface with the cuneate nucleus of macaques.

While the response properties of neurons in the somatosensory nerves and anterior parietal cortex have been extensively studied, little is known about the encoding of tactile and proprioceptive information in the cuneate nucleus (CN) or external cuneate nucleus (ECN), the first recipients of upper limb somatosensory afferent signals. The major challenge in characterizing neural coding in CN/ECN has been to record from these tiny, difficult-to-access brain stem structures. Most previous investigations of CN response properties have been carried out in decerebrate or anesthetized animals, thereby eliminating the well-documented top-down signals from cortex, which likely exert a strong influence on CN responses. Seeking to fill this gap in our understanding of somatosensory processing, we describe an approach to chronically implanting arrays of electrodes in the upper limb representation in the brain stem in primates. First, we describe the topography of CN/ECN in rhesus macaques, including its somatotopic organization and the layout of its submodalities (touch and proprioception). Second, we describe the design of electrode arrays and the implantation strategy to obtain stable recordings. Third, we show sample responses of CN/ECN neurons in brain stem obtained from awake, behaving monkeys. With this method, we are in a position to characterize, for the first time, somatosensory representations in CN and ECN of primates.NEW & NOTEWORTHY In primates, the neural basis of touch and of our sense of limb posture and movements has been studied in the peripheral nerves and in somatosensory cortex, but coding in the cuneate and external cuneate nuclei, the first processing stage for these signals in the central nervous system, remains an enigma. We have developed a method to record from these nuclei, thereby paving the way to studying how sensory information from the limb is encoded there.

(Invited) Multimodal Microelectrode Failure Analysis Reveals Complex Relationship at the Neural Interface

Penetrating microelectrode arrays that can record extracellular action potentials from small, targeted groups of neurons are critical for basic neuroscience research and emerging clinical applications. However, these electrode devices suffer from reliability and variability issues which impact their performance on the order of months to years. The failure mechanisms of these electrodes are understood to be a complex combination of the biotic and abiotic failure modes. The breaching of the blood–brain barrier (BBB) to insert devices triggers a cascade of biochemical pathways resulting in complex molecular and cellular responses to implanted devices. Molecular and cellular changes in the microenvironment surrounding an implant include the introduction of mechanical strain, BBB leakage, activation of glial cells, loss of perfusion, secondary metabolic injury, and neuronal degeneration. The resulting inflammation is a key hypothesized cause of neural recording failure. However, previous attempt so directly correlate recording performance, to impedance, and to histological outcomes have led counter-intuitive and sometimes conflicting outcomes. One reason is that many neurons remain quiescent during anesthetized or resting-state conditions. We previously demonstrated this by visually evoked stimulation paradigms of the contralateral eye in order to evaluate chronic recording performance of linear silicon electrode in the primary visual cortex. Additional, multiphoton analysis using GCaMP6 transgenic animals further confirmed these results. More recently, there has been a growing interesting recording during awake free-roaming conditions in the primary motor cortex in order to avoid resting-state related quiescent activity. However, this in turn leads to increases in Lenz’s Law related artefacts that have the same time constants and waveform shapes as action potentials in rodents, but not NHP. While behaviorally training animals to remain immobile could improve outcomes, it also introduces the potential for Experimenter Expectancy Effect bias on the outcomes. The visual stimulation paradigm enable the use of current source density analysis to electrophysiologically identify Layer II/III, IV, and V in the cortex. This, in turn, allowed correlation of electrophysiological layers to the histological layers based on section depth and the differences in neural morphology and density. Our findings from electrophysiology, impedance spectroscopy, and post-mortem histology demonstrate a very poor relationship between histology and impedance to electrophysiology. For example, tissue with low-levels of glial encapsulation, healthy neuronal proximity, and low impedance can still have poor recording performance, even with neural activity is behaviorally driven. Even when histology confirms a perfect tissue interface, cracking or delamination of insulation on the microelectrode has been linked to a drop in impedance and a loss of recording failure. In contrast, cracking of the electrical trace and delamination of the recording site has been linked to recording failure through a jump in electrical impedance. As such, several modes of mechanical failure of chronically implanted planar silicon electrodes were found that result in degradation and/or loss of recording. Our findings highlight the importance of strains and material properties of various subcomponents within an electrode array and the poor reliability of determining electrode viability through electrochemical impedance spectroscopy. Interestingly, we discovered in a number of situations that even with good neural density, uncompromised electrode material, and good impedances, recording performance can sometimes completely degrade. New multimodal analysis demonstrates the importance of capturing dynamic information, such as with in vivo multiphoton study, and that the presence of neurons does not guarantee functional neural activity over time. We further demonstrate that the foundation of assumptions and simplification made in the field for neural interface research are not true or incomplete. To solve the longstanding chronic neural interface problem, we need to first understand the complexity of the problem.

Self-organization of "fibro-axonal" composite tissue around unmodified metallic micro-electrodes can form a functioning interface with a peripheral nerve: A new direction for creating long-term neural interfaces.

A long-term peripheral neural interface is an area of intense research. The use of electrode interfaces is limited by the biological response to the electrode material. We created an electrode construct to harbor the rat sciatic nerve with interposition of autogenous adipose tissue between the nerve and the electrode. The construct was implanted for 10 weeks. Immunohistochemistry showed a unique laminar pattern of axonal growth layered between fibro-collagenous tissue, forming a physical interface with the tungsten micro-electrode. Action potentials transmitted across the intrerface showed mean conduction velocities varying between 6.99 ± 2.46 and 20.14 ± 4 m/s. We have demonstrated the feasibility of a novel peripheral nerve interface through modulation of normal biologic phenomena. It has potential applications as a chronic implantable neural interface.

Mechanically Adaptive Silicon-based Neural Probes for Chronic High-resolution Neural Recording

Ahybridly assembled, neural probe based on silicon (Si) with reduced dimensions and improved mechanical flexibility is proposed as a chronic neural interface. In contrast to previous approaches, the microelectrode arrayat the probe tip will be completely implanted into cortical tissue and tethered only by a slender and highly flexible, 11-μm-thick polyimide cable. The Si-based electrode arrays carry 16 or 32 channels and feature cross-sections as small as 50 × 120 μm2 across their entire length. Implantation of the flexible probes is facilitated by a temporary increase in probe stiffness using a bio-dissolvable polymer coating. The centrifuge-based molding of polyethylene glycol creates sharp insertion vehicles with a thickness of only 75 μm. Probe implantation up to 9 mm into agar-based brain models demonstrates the insertion capability of the novel mechanically adaptive neural probes.

The density difference between tissue and neural probes is a key factor for glial scarring

A key to successful chronic neural interfacing is to achieve minimal glial scarring surrounding the implants, as the astrocytes and microglia may functionally insulate the interface. A possible explanation for the development of these reactions is mechanical forces arising between the implants and the brain. Here, we show that the difference between the density of neural probes and that of the tissue, and the resulting inertial forces, are key factors for the development of the glial scar. Two probes of similar size, shape, surface structure and elastic modulus but differing greatly in density were implanted into the rat brain. After six weeks, significantly lower astrocytic and microglial reactions were found surrounding the low-density probes, approaching no reaction at all. This provides a major key to design fully biocompatible neural interfaces and a new platform for in vivo assays of tissue reactions to probes with differing materials, surface structures, and shapes.