Bioelectronic and neuroprosthetic interfaces rely on implanted microelectrode arrays (MEAs) to interact with the human body. Printing techniques, such as inkjet and screen printing, are attractive methods for the manufacturing of MEAs because they allow flexible, room‐temperature, scalable, and cost‐effective fabrication processes. Herein, the fabrication of all‐printed electrocorticography arrays made by inkjet printing of platinum and screen printing of polyimide is shown. Next, mechanical and electrochemical characterizations are performed. As a proof of concept, in vivo visually evoked cortical potentials are recorded in rabbits upon flash stimulation. Lastly, it is shown that the all‐printed electrocorticography arrays are not cytotoxic. Altogether, the results enable the use of printed MEAs for neurological applications.

Vision is an extraordinary sense through which we can appreciate the beauty of the world we live in, gain invaluable knowledge and communicate with others using visual expression and arts. On the contrary, blindness is a threatening medical condition disrupting the life of affected people and their families. Therefore, restoring sight is one of the open challenges of our society. Today, the synergistic convergence of science and technology holds the potential to provide blind patients with artificial vision using visual prostheses: a type of implantable medical device able to reactivate visual neurons using electrical stimulation. Although clinical trials showed that vision restoration is still far away, significant technological advances make visual prostheses a valuable solution for blind patients. This review is not only a description of the state-of-the-art. Instead, it provides the reader with an update on recent developments, a critical discussion of the open challenges, and an overview of promising future directions.

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.

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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 electrodes. First, we validated the higher stimulation selectivity of this new electrode array compared to classical monopolar stimulation using simulations. Next, we compared them in-vivo by intraneural stimulation of the rabbit optic nerve and recording evoked potentials in the primary visual cortex. Main results. Simulations showed that three-dimensional concentric bipolar electrodes provide a high localisation of the electric field in the tissue so that electrodes are electrically independent even for high electrode density. Experiments in-vivo highlighted 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 concentric bipolar electrodes improves selectivity in optic nerve stimulation. This approach is suitable for other neural applications, including bioelectronic medicine.

Dorsal column stimulation (DCS) of the spinal cord is emerging as a promising new technology for the treatment of Parkinson's disease (PD). However, the mechanisms underlying its therapeutic effect on PD symptoms are not fully understood. Here we demonstrate a closed-loop DCS (CLDCS) paradigm - a substantial advancement from previously tested continuous high-frequency DCS - in a bilateral intrastriatal 6-hydroxydopamine (6-ohda) rodent model of PD. Firstly, CLDCS performed significantly better than continuous open-loop DCS in ameliorating motor symptoms of PD. Secondly, the application of CLDCS triggered by corticostriatal beta frequency oscillations created a pro-locomotion brain state that reduced akinesia. Finally, CLDCS was better at disrupting beta oscillations in the corticostriatal areas and achieved it with lesser overall charge delivery than continuous open-loop stimulation. These results indicate that CLDCS is remarkably better than traditional spinal cord stimulation methods and has the potential to be highly effective in treating PD symptoms. We envision that the CLDCS approach can be beneficial in the treatment of other neurological disorders which showcase similar pathological neuronal oscillations.

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 degrees. 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 leap forward for intraneural optic nerve stimulation towards artificial vision.

Off-stoichiometry thiol-ene-epoxy (OSTE+) thermosets have recently gained attention for the rapid prototyping of microfluidic chips because they show low permeability to gases and little absorption of dissolved molecules, they allow direct low-temperature dry bonding without surface treatments, they have a low Young's modulus, and they can be manufactured via UV polymerisation. The compatibility with standard clean-room processes and the 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 device 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 implantation. This work introduces OSTE+ as a promising material in the field of implantable neural interfaces.