In vivodeployment of mechanically adaptive nanocomposites for intracortical microelectrodes

Abstract

We recently introduced a series of stimuli-responsive, mechanically-adaptive polymer nanocomposites. Here, we report the first application of these bio-inspired materials as substrates for intracortical microelectrodes. Our hypothesis is that the ideal electrode should be initially stiff to facilitate minimal trauma during insertion into the cortex, yet becomes mechanically compliant to match the stiffness of the brain tissue and minimize forces exerted on the tissue, attenuating inflammation. Microprobes created from mechanically reinforced nanocomposites demonstrated a significant advantage compared to model microprobes composed of neat polymer only. The nanocomposite microprobes exhibit a higher storage modulus (E’ = ~5 GPa) than the neat polymer microprobes (E’ = ~2 GPa) and could sustain higher loads (~17 mN), facilitating penetration through the pia mater and insertion into the cerebral cortex of a rat. In contrast, the neat polymer microprobes mechanically failed under lower loads (~7 mN) before they were capable of inserting into cortical tissue. Further, we demonstrated the material’s ability to morph while in the rat cortex to more closely match the mechanical properties of the cortical tissue. Nanocomposite microprobes that were implanted into the rat cortex for up to 8 weeks demonstrated increased cell density at the microelectrode-tissue interface and a lack of tissue necrosis or excessive gliosis. This body of work introduces our nanocomposite-based microprobes as adaptive substrates for intracortical microelectrodes and potentially other biomedical applications.

Soft, Flexible Freestanding Neural Stimulation and Recording Electrodes Fabricated from Reduced Graphene Oxide

“…[12] Contributing factors believed to adversely affect the quality of the electrode-tissue interface in a chronic time window include electrode size, [13,14] density of electrode material, [15] skull tethering mechanisms and associated micromotion of the implant, [16] and mechanical compliance of the electrode itself. [17,18] Considering the aforementioned characteristics, the ideal implantable electrode will be small, soft, mechanically-strong, and have a density similar to neural tissue. Present implantable electrodes are made from rigid materials such as noble metals, stainless steel, or crystalline silicon, though the density and stiffness of these materials render them non-ideal for chronic interaction with neural tissue.…”

Environmentally-controlled Microtensile Testing of Mechanically-adaptive Polymer Nanocomposites for <em>ex vivo</em> Characterization

“…Further, stimuli-responsive materials may quickly recover their initial stiffness after explantation. Therefore, we have developed a method by which the mechanical properties of implanted microsamples can be measured ex vivo, with simulated physiological conditions maintained using moisture and temperature control 13,16,17 .…”

“…To this end, a custom microtensile tester was designed to accommodate microscale samples 13,17 with widely-varying Young's moduli (range of 10 MPa to 5 GPa). As our interests are in the application of PVAc-NC as a biologically-adaptable neural probe substrate, a tool capable of mechanical characterization of samples at the microscale was necessary.…”

“…As our interests are in the application of PVAc-NC as a biologically-adaptable neural probe substrate, a tool capable of mechanical characterization of samples at the microscale was necessary. This tool was adapted to provide humidity and temperature control, which minimized sample drying and cooling 17 . As a result, the mechanical characteristics of the explanted sample closely reflect those of the sample just prior to explantation.…”

“…Further, stimuli-responsive materials may quickly recover their initial stiffness after explantation. Therefore, we have developed a method by which the mechanical properties of implanted microsamples can be measured ex vivo, with simulated physiological conditions maintained using moisture and temperature control 13,16,17 .To this end, a custom microtensile tester was designed to accommodate microscale samples 13,17 with widely-varying Young's moduli (range of 10 MPa to 5 GPa). As our interests are in the application of PVAc-NC as a biologically-adaptable neural probe substrate, a tool capable of mechanical characterization of samples at the microscale was necessary.…”