Electrical signals recorded from neurons by intracortical electrodes have been used by human patients to communicate with computers and to control robotic limbs. The signal quality and longevity of recordable signals are inconsistent. There is increasing evidence indicating that the neuro-inflammatory response may be a primary hurdle to consistently obtaining high quality recordings. Within the brain, cells are living in the elastic extracellular matrix (ECM) meshwork with 3D and high aspect ratio fibrillary protein structures. This environment is textured and compliant, not smooth or stiff. In contrast, to the currently accepted and used surfaces of intracortical microelectrodes. The discontinuity between the architecture and stiffness of the tissue and device results in the initial inflammatory and chronic foreign body response to the implant. Current research aimed at alleviating the inflammatory response, as well as improving the neuronal signal from electrodes, focuses on either therapeutic or materials-based solutions. Limited emphasis has been placed on combinatorial approaches that mimic the physical properties of the native ECM, including the architecture and stiffness. The current proposal seeks to progress the training of Dr. Ereifej where the CDA-1 training left off, ensuring continuity. The candidates CDA-1 preliminary work has successfully etched surface modifications based on the architecture (but not orientation) of native brain tissue onto non-functional silicon Michigan style shanks. It was shown that implants etched with nanoscale surface modifications were able to decrease glial cell activation and increase neuronal viability around the implant site over time. However, Dr. Ereifej has yet to: 1) characterize the long-term effects or 2) evaluate various orientations of lines, to determine the optimal surface modifications. Given the documented role that substrate stiffness has on cellular response to materials, it is also imperative to evaluate the configurations on materials with a modulus similar to brain tissue. Therefore, the central hypothesis to this proposal is that microelectrodes that more closely mimic the architecture and modulus of native brain tissue will result in improved biocompatibility, displayed through a reduced chronic inflammatory response, improved long-term recording stability, and decreased motor deficits. We propose to first characterize the neuroinflammatory, electrophysiological and motor behavior response evoked by chronic implantation of intracortical microelectrodes etched with surface modifications. This aim will test the hypothesis that microelectrodes etched with surface modifications mimicking that of the native environment will result in a reduced neuroinflammatory response of the surrounding tissue, improved stability of recorded neuronal signals and result in less motor deficits compared to control animals. Specific Aim 1 will utilize the neural implants with the bio-inspired surface arch...