Conformable neural interface based on off-stoichiometry thiol-ene-epoxy thermosets.

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.

POLYRETINA restores light responses in vivo in blind Göttingen minipigs.

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.

Three-dimensional multilayer concentric bipolar electrodes restrict spatial activation in optic nerve stimulation.

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.

All-polymeric transient neural probe for prolonged in-vivo electrophysiological recordings.

Transient bioelectronics has grown fast, opening possibilities never thought before. In medicine, transient implantable devices are interesting because they could eliminate the risks related to surgical retrieval and reduce the chronic foreign body reaction. Despite recent progress in this area, the potential of transient bioelectronics is still limited by their short functional lifetime owed to the fast dissolution rate of degradable metals, which is typically a few days or weeks. Here we report that a switch from degradable metals to an entirely polymer-based approach allows for a slower degradation process and a longer lifetime of the transient probe, thus opening new possibilities for transient medical devices. As a proof-of-concept, we fabricated all-polymeric transient neural probes that can monitor brain activity in mice for a few months, rather than a few days or weeks. Also, we extensively evaluated the foreign body reaction around the implant during the probe degradation. This kind of devices might pave the way for several applications in neuroprosthetics.

A machine-learning algorithm correctly classifies cortical evoked potentials from both visual stimulation and electrical stimulation of the optic nerve.

Objective. Optic nerve's intraneural stimulation is an emerging neuroprosthetic approach to provide artificial vision to totally blind patients. An open question is the possibility to evoke individual non-overlapping phosphenes via selective intraneural optic nerve stimulation. To begin answering this question, first, we aim at showing in preclinical experiments with animals that each intraneural electrode could evoke a distinguishable activity pattern in the primary visual cortex.Approach. We performed both patterned visual stimulation and patterned electrical stimulation in healthy rabbits while recording evoked cortical activity with an electrocorticogram array in the primary visual cortex. Electrical stimulation was delivered to the optic nerve with the intraneural array OpticSELINE. We used a support vector machine algorithm paired to a linear regression model to classify cortical responses originating from visual stimuli located in different portions of the visual field and electrical stimuli from the different electrodes of the OpticSELINE.Main results. Cortical activity induced by visual and electrical stimulation could be classified with nearly 100% accuracy relative to the specific location in the visual field or electrode in the array from which it originated. For visual stimulation, the accuracy increased with the separation of the stimuli and reached 100% for separation higher than 7°. For electrical stimulation, at low current amplitudes, the accuracy increased with the distance between electrodes, while at higher current amplitudes, the accuracy was nearly 100% already for the shortest separation.Significance. Optic nerve's intraneural stimulation with the OpticSELINE induced discernible cortical activity patterns. These results represent a necessary condition for an optic nerve prosthesis to deliver vision with non-overlapping phosphene. However, clinical investigations will be required to assess the translation of these results into perceptual phenomena.