Prefrontal electrophysiological biomarkers and mechanism-based drug effects in a rat model of alcohol addiction.

Patients with alcohol use disorder (AUD) who seek treatment show highly variable outcomes. A precision medicine approach with biomarkers responsive to new treatments is warranted to overcome this limitation. Promising biomarkers relate to prefrontal control mechanisms that are severely disturbed in AUD.

Electrically Controlled Click-Chemistry for Assembly of Bioactive Hydrogels on Diverse Micro- and Flexible Electrodes.

The seamless integration of electronics with living matter requires advanced materials with programmable biological and engineering properties. Here electrochemical methods to assemble semi-synthetic hydrogels directly on electronically conductive surfaces are explored. Hydrogels consisting of poly (ethylene glycol) (PEG) and heparin building blocks are polymerized by spatially controlling the click reaction between their thiol and maleimide moieties.

Electro-assisted printing of soft hydrogels via controlled electrochemical reactions.

Hydrogels underpin many applications in tissue engineering, cell encapsulation, drug delivery and bioelectronics. Methods improving control over gelation mechanisms and patterning are still needed. Here we explore a less-known gelation approach relying on sequential electrochemical-chemical-chemical (ECC) reactions.

A Multimodal Neuroprosthetic Interface to Record, Modulate and Classify Electrophysiological Biomarkers Relevant to Neuropsychiatric Disorders.

Most mental disorders, such as addictive diseases or schizophrenia, are characterized by impaired cognitive function and behavior control originating from disturbances within prefrontal neural networks. Their often chronic reoccurring nature and the lack of efficient therapies necessitate the development of new treatment strategies. Brain-computer interfaces, equipped with multiple sensing and stimulation abilities, offer a new toolbox whose suitability for diagnosis and therapy of mental disorders has not yet been explored.

Rapid prototyping of soft bioelectronic implants for use as neuromuscular interfaces.

Neuromuscular interfaces are required to translate bioelectronic technologies for application in clinical medicine. Here, by leveraging the robotically controlled ink-jet deposition of low-viscosity conductive inks, extrusion of insulating silicone pastes and in situ activation of electrode surfaces via cold-air plasma, we show that soft biocompatible materials can be rapidly printed for the on-demand prototyping of customized electrode arrays well adjusted to specific anatomical environments, functions and experimental models. We also show, with the monitoring and activation of neuronal pathways in the brain, spinal cord and neuromuscular system of cats, rats and zebrafish, that the printed bioelectronic interfaces allow for long-term integration and functional stability.

Cytocompatible, Injectable, and Electroconductive Soft Adhesives with Hybrid Covalent/Noncovalent Dynamic Network.

Synthetic conductive biopolymers have gained increasing interest in tissue engineering, as they can provide a chemically defined electroconductive and biomimetic microenvironment for cells. In addition to low cytotoxicity and high biocompatibility, injectability and adhesiveness are important for many biomedical applications but have proven to be very challenging. Recent results show that fascinating material properties can be realized with a bioinspired hybrid network, especially through the synergy between irreversible covalent crosslinking and reversible noncovalent self-assembly.

Highly Conductive, Stretchable, and Cell-Adhesive Hydrogel by Nanoclay Doping.

Electrically conductive materials that mimic physical and biological properties of tissues are urgently required for seamless brain-machine interfaces. Here, a multinetwork hydrogel combining electrical conductivity of 26 S m , stretchability of 800%, and tissue-like elastic modulus of 15 kPa with mimicry of the extracellular matrix is reported. Engineering this unique set of properties is enabled by a novel in-scaffold polymerization approach.

Spatiotemporal neuromodulation therapies engaging muscle synergies improve motor control after spinal cord injury.

Electrical neuromodulation of lumbar segments improves motor control after spinal cord injury in animal models and humans. However, the physiological principles underlying the effect of this intervention remain poorly understood, which has limited the therapeutic approach to continuous stimulation applied to restricted spinal cord locations. Here we developed stimulation protocols that reproduce the natural dynamics of motoneuron activation during locomotion.

Biomaterials. Electronic dura mater for long-term multimodal neural interfaces.

The mechanical mismatch between soft neural tissues and stiff neural implants hinders the long-term performance of implantable neuroprostheses. Here, we designed and fabricated soft neural implants with the shape and elasticity of dura mater, the protective membrane of the brain and spinal cord. The electronic dura mater, which we call e-dura, embeds interconnects, electrodes, and chemotrodes that sustain millions of mechanical stretch cycles, electrical stimulation pulses, and chemical injections.

A microchannel neuroprosthesis for bladder control after spinal cord injury in rat.

A severe complication of spinal cord injury is loss of bladder function (neurogenic bladder), which is characterized by loss of bladder sensation and voluntary control of micturition (urination), and spontaneous hyperreflexive voiding against a closed sphincter (detrusor-sphincter dyssynergia). A sacral anterior root stimulator at low frequency can drive volitional bladder voiding, but surgical rhizotomy of the lumbosacral dorsal roots is needed to prevent spontaneous voiding and dyssynergia. However, rhizotomy is irreversible and eliminates sexual function, and the stimulator gives no information on bladder fullness.

Corticospinal neuroprostheses to restore locomotion after spinal cord injury.

In this conceptual review, we highlight our strategy for, and progress in the development of corticospinal neuroprostheses for restoring locomotor functions and promoting neural repair after thoracic spinal cord injury in experimental animal models. We specifically focus on recent developments in recording and stimulating neural interfaces, decoding algorithms, extraction of real-time feedback information, and closed-loop control systems. Each of these complex neurotechnologies plays a significant role for the design of corticospinal neuroprostheses.

Localization of folds and cracks in thin metal films coated on flexible elastomer foams.

Thin metal films coated on soft elastomeric foam substrates exhibit enhanced electromechanical performance. The open-cell foam structure conveys highly anisotropic mechanical properties within the top, thin capping elastomer at the surface of the foam. Upon stretching, large strain fields inducing cracks and folds localize above the foam cells, while the surrounding cell ligaments remain almost strain-free, enabling stable electrical conduction in the metallic coating.

Interaction of glia with a compliant, microstructured silicone surface.

Soft bioengineered surfaces offer a route towards modulating the tissue responses to chronically implanted devices and may enhance their functionality. In this communication we fabricate microtopographically rich and mechanically compliant silicone surfaces for use in soft neural interfaces. We observe the interaction of primary rat microglia and astroglia with arrays of tall and short (4.

Concurrent recordings of bladder afferents from multiple nerves using a microfabricated PDMS microchannel electrode array.

In this paper we present a compliant neural interface designed to record bladder afferent activity. We developed the implant's microfabrication process using multiple layers of silicone rubber and thin metal so that a gold microelectrode array is embedded within four parallel polydimethylsiloxane (PDMS) microchannels (5 mm long, 100 μm wide, 100 μm deep). Electrode impedance at 1 kHz was optimized using a reactive ion etching (RIE) step, which increased the porosity of the electrode surface.

High sensitivity recording of afferent nerve activity using ultra-compliant microchannel electrodes: an acute in vivo validation.

Neuroprostheses interfaced with transected peripheral nerves are technological routes to control robotic limbs as well as convey sensory feedback to patients suffering from traumatic neural injuries or degenerative diseases. To maximize the wealth of data obtained in recordings, interfacing devices are required to have intrafascicular resolution and provide high signal-to-noise ratio (SNR) recordings. In this paper, we focus on a possible building block of a three-dimensional regenerative implant: a polydimethylsiloxane (PDMS) microchannel electrode capable of highly sensitive recordings in vivo.