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Off-stoichiometry thiol-ene-epoxy (OSTE+) thermosets show low permeability to gases and little absorption of dissolved molecules, allow direct low-temperature dry bonding without surface treatments, have a low Young's modulus, and can be manufactured via UV polymerisation. For these reasons, OSTE+ thermosets have recently gained attention for the rapid prototyping of microfluidic chips. Moreover, their compatibility with standard clean-room processes and outstanding mechanical properties make OSTE+ an excellent candidate as a novel material for neural implants. Here we exploit OSTE+ to manufacture a conformable multilayer micro-electrocorticography array with 16 platinum electrodes coated with platinum black. The mechanical properties allow conformability to curved surfaces such as the brain. The low permeability and strong adhesion between layers improve the stability of the device. Acute experiments in mice show the multimodal capacity of the array to record and stimulate the neural tissue by smoothly conforming to the mouse cortex. Devices are not cytotoxic, and immunohistochemistry stainings reveal only modest foreign body reaction after two and six weeks of chronic implantation. This work introduces OSTE+ as a promising material for implantable neural interfaces.

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Retinal prostheses hold the potential for artificial vision in blind people affected by incurable diseases of the outer retinal layer. Available technologies provide only a small field of view: a significant limitation for totally blind people. To overcome this problem, we recently proposed a large and high-density photovoltaic epiretinal device, known as POLYRETINA. Here, we report the in vivo assessment of POLYRETINA. First, we characterise a model of chemically-induced blindness in Göttingen minipigs. Then, we develop and test a minimally invasive injection procedure to insert the large epiretinal implant into the eye. Last, we show that POLYRETINA restores light-evoked cortical responses in blind animals at safe irradiance levels. These results indicate that POLYRETINA holds the potential for artificial vision in totally blind patients affected by retinitis pigmentosa.

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Objective.Intraneural nerve interfaces often operate in a monopolar configuration with a common and distant ground electrode. This configuration leads to a wide spreading of the electric field. Therefore, this approach is suboptimal for intraneural nerve interfaces when selective stimulation is required.Approach.We designed a multilayer electrode array embedding three-dimensional concentric bipolar (CB) electrodes. First, we validated the higher stimulation selectivity of this new electrode array compared to classical monopolar stimulation using simulations. Next, we compared themin-vivoby intraneural stimulation of the rabbit optic nerve and recording evoked potentials in the primary visual cortex.Main results.Simulations showed that three-dimensional CB electrodes provide a high localisation of the electric field in the tissue so that electrodes are electrically independent even for high electrode density. Experimentsin-vivohighlighted that this configuration restricts spatial activation in the visual cortex due to the fewer fibres activated by the electric stimulus in the nerve.Significance.Highly focused electric stimulation is crucial to achieving high selectivity in fibre activation. The multilayer array embedding three-dimensional CB electrodes improves selectivity in optic nerve stimulation. This approach is suitable for other neural applications, including bioelectronic medicine.

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Objective.Retinal stimulation in blind patients evokes the sensation of discrete points of light called phosphenes, which allows them to perform visually guided tasks, such as orientation, navigation, object recognition, object manipulation and reading. However, the clinical benefit of artificial vision in profoundly blind patients is still tenuous, as several engineering and biophysical obstacles keep it far away from natural perception. The relative preservation of the inner retinal neurons in hereditary degenerative retinal diseases, such as retinitis pigmentosa, supports artificial vision through the network-mediated stimulation of retinal ganglion cells (RGCs). However, the response of RGCs to repeated electrical stimulation rapidly declines, primarily because of the intrinsic desensitisation of their excitatory network. In patients, upon repetitive stimulation, phosphenes fade out in less than half of a second, which drastically limits the understanding of the percept.Approach.A more naturalistic stimulation strategy, based on spatiotemporal modulation of electric pulses, could overcome the desensitisation of RGCs. To investigate this hypothesis, we performed network-mediated epiretinal stimulations paired to electrophysiological recordings in retinas explanted from both male and female retinal degeneration 10 mice.Main results.The results showed that the spatial and temporal modulation of the network-mediated epiretinal stimulation prolonged the persistence of the RGC's response from 400 ms up to 4.2 s.Significance.A time-varied, non-stationary and interrupted stimulation of the retinal network, mimicking involuntary microsaccades, might reduce the fading of the visual percept and improve the clinical efficacy of retinal implants.

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OBJECTIVE: In many applications, multielectrode arrays employed as neural implants require a high density and a high number of electrodes to precisely record and stimulate the activity of the nervous system while preserving the overall size of the array. APPROACH: Here we present a multilayer and three-dimensional (3D) electrode array, together with its manufacturing method, enabling a higher electrode density and a more efficient signal transduction with the biological tissue. MAIN RESULTS: The 3D structure of the electrode array allows for a multilayer placement of the interconnects within a flexible substrate, it narrows the probe size per the same number of electrodes, and it maintains the electrode contacts at the same level within the tissue. In addition, it augments the electrode surface area, leading to a lower electrochemical impedance and a higher charge storage capacity. To characterize the recordings capabilities of the multilayer 3D electrodes, we measured visually evoked cortical potentials in mice and analysed the evolution of the peak prominences and latencies according to different light intensities and recording depths within the brain. The resulting signal-to-noise ratio is improved compared to flat electrodes. Finally, the 3D electrodes have been imaged inside a clarified mouse brain using a light-sheet microscope to visualize their integrity within the tissue. SIGNIFICANCE: The multilayer 3D electrodes have proved to be a valid technology to ensure tissue proximity and higher recording/stimulating efficiencies while enabling higher electrode density and reducing the probe size.

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Reducing the mechanical mismatch between the stiffness of a neural implant and the softness of the neural tissue is still an open challenge in neuroprosthetics. The emergence of conductive hydrogels in the last few years has considerably widened the spectrum of possibilities to tackle this issue. Nevertheless, despite the advancements in this field, further improvements in the fabrication of conductive hydrogel-based electrodes are still required. In this work, we report the fabrication of a conductive hydrogel-based microelectrode array for neural recording using a hybrid material composed of poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate), and alginate. The mechanical properties of the conductive hydrogel have been investigated using imaging techniques, while the electrode arrays have been electrochemically characterized at each fabrication step, and successfully validated both in vitro and in vivo. The presence of the conductive hydrogel, selectively electrodeposited onto the platinum microelectrodes, allowed achieving superior electrochemical characteristics, leading to a lower electrical noise during recordings. These findings represent an advancement in the design of soft conductive electrodes for neuroprosthetic applications.

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Retinal prostheses have been developed to fight blindness in people affected by outer retinal layer dystrophies. To date, few hundred patients have received a retinal implant. Inspired by intraocular lenses, we have designed a foldable and photovoltaic wide-field epiretinal prosthesis (named POLYRETINA) capable of stimulating wireless retinal ganglion cells. Here we show that within a visual angle of 46.3 degrees, POLYRETINA embeds 2215 stimulating pixels, of which 967 are in the central area of 5 mm, it is foldable to allow implantation through a small scleral incision, and it has a hemispherical shape to match the curvature of the eye. We demonstrate that it is not cytotoxic and respects optical and thermal safety standards; accelerated ageing shows a lifetime of at least 2 years. POLYRETINA represents significant progress towards the improvement of both visual acuity and visual field with the same device, a current challenging issue in the field.

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