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The effectiveness of state-of-the-art systemic treatments for neurological disorders is hampered not only by the difficulty in crossing the blood brain barrier but also off-target drug interactions. In this study, a delivery method is simulated for a novel U-shaped microtube locally infusing drugs directly into the extracellular space of the brain and relying on diffusion as a transport mechanism. The influence of flow rate, drug properties and device geometry are investigated. It is anticipated that these findings will accelerate progress on both developmental and applied drug delivery and materials research. Graphical abstract

Bioelectronics hold the key for understanding and treating disease. However, achieving stable, long-term interfaces between electronics and the body remains a challenge. Implantation of a bioelectronic device typically initiates a foreign body response, which can limit long-term recording and stimulation efficacy. Techniques from regenerative medicine have shown a high propensity for promoting integration of implants with surrounding tissue, but these implants lack the capabilities for the sophisticated recording and actuation afforded by electronics. Combining these two fields can achieve the best of both worlds. Here, we show the construction of a hybrid implant system for creating long-term interfaces with tissue. We create implants by combining a microelectrode array with a bioresorbable and remodellable gel. These implants are shown to produce a minimal foreign body response when placed into musculature, allowing us to record long-term electromyographic signals with high spatial resolution. This device platform drives the possibility for a new generation of implantable electronics for long-term interfacing. This article is protected by copyright. All rights reserved.

Electronics that change shape inside the body enable keyhole surgery of spinal implants that can treat severe pain., Spinal cord stimulation is one of the oldest and most established neuromodulation therapies. However, today, clinicians need to choose between bulky paddle-type devices, requiring invasive surgery under general anesthetic, and percutaneous lead–type devices, which can be implanted via simple needle puncture under local anesthetic but offer clinical drawbacks when compared with paddle devices. By applying photo- and soft lithography fabrication, we have developed a device that features thin, flexible electronics and integrated fluidic channels. This device can be rolled up into the shape of a standard percutaneous needle then implanted on the site of interest before being expanded in situ, unfurling into its paddle-type conformation. The device and implantation procedure have been validated in vitro and on human cadaver models. This device paves the way for shape-changing bioelectronic devices that offer a large footprint for sensing or stimulation but are implanted in patients percutaneously in a minimally invasive fashion.

Implantable electrophoretic drug delivery devices have shown promise for applications ranging from treating pathologies such as epilepsy and cancer to regulating plant physiology. Upon applying a voltage, the devices electrophoretically transport charged drug molecules across an ion‐conducting membrane out to the local implanted area. This solvent‐flow‐free “dry” delivery enables controlled drug release with minimal pressure increase at the outlet. However, a major challenge these devices face is limiting drug leakage in their idle state. Here, a method of reducing passive drug leakage through the choice of the drug co‐ion is presented. By switching acetylcholine's associated co‐ion from chloride to carboxylate co‐ions as well as sulfopropyl acrylate‐based polyanions, steady‐state drug leakage rate is reduced up to sevenfold with minimal effect on the active drug delivery rate. Numerical simulations further illustrate the potential of this method and offer guidance for new material systems to suppress passive drug leakage in electrophoretic drug delivery devices., Drug leakage is a safety concern for long‐term implantable electrophoretic drug delivery devices. In this work, co‐ion engineering is proposed as a clinically viable method to drastically reduce drug leakage rate, without any sacrifices on the device active performance. The co‐ion engineering method is drug‐independent and can be readily applied to existing electrophoretic drug delivery devices.

Electrophoretic drug delivery devices are able to deliver drugs with exceptional temporal and spatial precision. This technology has emerged as a promising platform for treating pathologies ranging from neuropathic pain to epilepsy. As the range of applications continues to expand, there is an urgent need to understand the underlying physics and estimate materials and device parameters for optimal performance. Here, computational modeling of the electrophoretic drug delivery device is carried out. Three critical performance indices, namely, the amount of drug transported, the pumping efficiency and the ON/OFF ratio are investigated as a function of initial drug concentration in the device and fixed charge concentration in the ion exchange membrane. The results provide guidelines for future materials and device design with an eye towards tailoring device performance to match disease-specific demands.

Local drug delivery directly to the source of a given pathology using retrodialysis is a promising approach to treating otherwise untreatable diseases. As the primary material component in retrodialysis, the semipermeable membrane represents a critical point for innovation. This work presents a new ionic hydrogel based on polyethylene glycol and acrylate with dopamine counterions. The ionic hydrogel membrane is shown to be a promising material for controlled diffusive delivery of dopamine. The ionic nature of the membrane accelerates uptake of cationic species compared to a nonionic membrane of otherwise similar composition. It is demonstrated that the increased uptake of cations can be exploited to confer an accelerated transport of cationic species between reservoirs as is desired in retrodialysis applications. This effect is shown to enable nearly 10-fold increases in drug delivery rates from low concentration solutions. The processability of the membrane is found to allow for integration with microfabricated devices which will in turn accelerate adaptation into both existing and emerging device modalities. It is anticipated that a similar materials design approach may be broadly applied to a variety of cationic and anionic compounds for drug delivery applications ranging from neurological disorders to cancer. - EPSRC (EP/S009000/1) - Marie Sklodowska-Curie Grant Agreement No. 823989. - Borysiewicz Biomedical Sciences Fellowship program. - Marie SklodowskaCurie IF BIKE Project No. 742865.

© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim The challenge of treating neurological disorders has motivated the development of implantable devices that can deliver treatment when and where it is needed. This study presents a novel brain implant capable of electrophoretically delivering drugs and recording local neural activity on the surface of the brain. The drug delivery is made possible by the integration of a microfluidic ion pump (µFIP) into a conformable electrocorticography (ECoG) device with recording cites embedded next to the drug delivery outlets. The µFIP ECoG device can deliver a high capacity of several biologically important cationic species on demand. The therapeutic potential of the device is demonstrated by using it to deliver neurotransmitters in a rodent model while simultaneously recording local neural activity. These developments represent a significant step forward for cortical drug-delivery systems.

Minimally invasive electrodes of cellular scale that approach a bio-integrative level of neural recording could enable the development of scalable brain machine interfaces that stably interface with the same neural populations over long period of time.In this paper, we designed and created NeuroRoots, a bio-mimetic multi-channel implant sharing similar dimension (10µm wide, 1.5µm thick), mechanical flexibility and spatial distribution as axon bundles in the brain. A simple approach of delivery is reported based on the assembly and controllable immobilization of the electrode onto a 35µm microwire shuttle by using capillarity and surface-tension in aqueous solution. Once implanted into targeted regions of the brain, the microwire was retracted leaving NeuroRoots in the biological tissue with minimal surgical footprint and perturbation of existing neural architectures within the tissue. NeuroRoots was implanted using a platform compatible with commercially available electrophysiology rigs and with measurements of interests in behavioral experiments in adult rats freely moving into maze. We demonstrated that NeuroRoots electrodes reliably detected action potentials for at least 7 weeks and the signal amplitude and shape remained relatively constant during long-term implantation.This research represents a step forward in the direction of developing the next generation of seamless brain-machine interface to study and modulate the activities of specific sub-populations of neurons, and to develop therapies for a plethora of neurological diseases.

An implantable microfluidic ion pump prevents seizures in a mice by delivery of inhibitory neurotransmitters to the seizure source., The persistence of intractable neurological disorders necessitates novel therapeutic solutions. We demonstrate the utility of direct in situ electrophoretic drug delivery to treat neurological disorders. We present a neural probe incorporating a microfluidic ion pump (μFIP) for on-demand drug delivery and electrodes for recording local neural activity. The μFIP works by electrophoretically pumping ions across an ion exchange membrane and thereby delivers only the drug of interest and not the solvent. This “dry” delivery enables precise drug release into the brain region with negligible local pressure increase. The therapeutic potential of the μFIP probe is tested in a rodent model of epilepsy. The μFIP probe can detect pathological activity and then intervene to stop seizures by delivering inhibitory neurotransmitters directly to the seizure source. We anticipate that further tailored engineering of the μFIP platform will enable additional applications in neural interfacing and the treatment of neurological disorders.

Neuroinspired device architectures offer the potential of higher order functionalities in information processing beyond their traditional microelectronic counterparts. Here we demonstrate a neuromorphic function of orientation selectivity, which is inspired from the visual system, with a combination of organic photodetectors and a multi-gated organic electrochemical transistor based on poly(3,4ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS). The device platform responds preferably to different orientations of light bars, a behaviour that resembles orientation selectivity of visual cortex cells. These results pave the way for organic-based neuromorphic devices with spatially correlated functionalities and potential applications in the area of organic bioelectronics.