A mimetic implant for low perturbation, stable stimulation and recording of neural units inside the brain.

Periodic Reporting for period 4 - BRAIN MICRO SNOOPER (A mimetic implant for low perturbation, stable stimulation and recording of neural units inside the brain.)

Berichtszeitraum: 2020-02-01 bis 2022-01-31

To deal with the problematic of Central Nervous System dysfunction and associated pathologies that can be traumatic (eg, accidents, vascular lesions), psychological (eg, autism, depression, anorexia, bipolar disorder), neurodegenerative (eg Parkinson's, Alzheimer's, Huntington's) or tumor-related (eg glioblastoma, medulloblastoma neuromas), the development of brain implants is crucial to better decipher neuronal information and intervene very thinly on neural networks using microstimulation. This project aim was to address two major challenges: to achieve the realization of a highly mechanically stable implant, allowing long term connection between neurons and microelectrodes and to provide neural implants with a high temporal and spatial resolution. To do so, the present project aim was to develop implants with structural and mechanical properties that resemble those of the natural brain environment. According to the literature, using electrodes and electric leads with a size of a few microns allows for a better neural tissue reconstruction around the implant. Also, the mechanical mismatch between the usually stiff implant material and the soft brain tissue affects the adhesion between tissue cells and electrodes. Here the objective was to implant a highly flexible free-floating microelectrode array in the brain tissue, through methods using micro-nanotechnology steps as well as a combination of polymers. Moreover, the literature and preliminary studies indicate that some surface chemistries and nanotopographies can promote neurite outgrowth while limiting glial cell proliferation. Implants nanostructuration was to be studied so as to help the neural tissue growth and to provide implants with a highly adhesive property, which will ensure its stable contact with the brain neural tissue over time. Implants with different microelectrode configurations (size and shape of wires) were to be tested in vitro and in vivo for their biocompatibility and their ability to record and stimulate neurons with high stability. This project final aim was to produce high-performance generic implants that can be used for various fundamental studies and applications, including neural prostheses and brain machine interfaces

The seven-person team working on the project started the work about the implant fabrication, assembling with electronics, in vitro biocompatibility studies and surgical method for the implant insertion. This last step was risky, given the tiny dimensions of the soft leads of the implant. We were in a first step, able to encapsulate them within a biodegradable material that facilitate their implantation and then gradually resorb. We performed the pre-clinical studies where two surgical procedures have been tested. One implied the use of a stiff shuttle to which the implant is stuck using PEG and as this PEG dissolves in tissues, we can remove the shuttle and let the implant into the cortical layers. This first technique was too invasive for the tissues. The second procedure is the one using PLGA, a biodegradable material FDA approved for certain applications that facilitate the implantation of the leads and then gradually resorb. The PLGA is attached to the soft leads using an original procedure. One challenge was to be able to control the geometries of the PLGA material to shape it as needles and to control the amount of PLGA inserted in tissues. We have used clean-room protocols to obtain tiny needles with a desirable shape. We chose specific dimensions (a few mm long, 100µm thick and 900µm large at the base of the needle) and controlled their stiffness allowing their insertion. We first studied the effect of the PLGA degradation alone, without the soft electrode leads, in the cortical tissues. We also looked at the effect of the speed insertion of the needle and showed that insertion of electrodes attached to the PLGA needles lead to small glial scars, mostly regardless the tested speeds. In parallel with the pre-clinical studies, the work in implant fabrication optimization was continued by evaluating the possibility to nanostructure the implant polymer and electrodes. It was possible to obtain nanostructured electrodes as well as to nanostructure one side of the implant. The electrode characterization showed that the nanostructuration led to decrease their impedance, this explained by the greater surface of exchange for charges. We obtained the In vivo detection of local field potentials and action potentials. Also, our In vitro tests showed that the adhesion of neural cells is highly enhanced when patterning a certain polymer type with nanostructuration.
The work that is described above will lead to 5 publications in peer-reviewed journals.

In conclusion, we have produced generic implants (with a possible polymer nanostructuration) that can be used for various fundamental studies and applications.

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Scanning electron microscopy and optical microscopy pictures of the implant electrode wires

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Periodic Reporting for period 4 - BRAIN MICRO SNOOPER (A mimetic implant for low perturbation, stable stimulation and recording of neural units inside the brain.)

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