In this study, we created a new method of electrospinning capable of controlling the surface structure of individual fibers (fiber nanotopography). The nanotopographical features were created by a phase separation in the fibers as they formed. To control the phase separation, a nonsolvent (a chemical insoluble with the polymer) was added to an electrospinning solution containing poly-l-lactic acid (PLLA) and chloroform. The nanotopography of electrospun fibers in the PLLA/chloroform solution was smooth. However, adding a small weight (<2% of total solution) of a single nonsolvent (water, ethanol, or dimethyl sulfoxide) generated nanoscale depressions on the surface of the fibers unique to the nonsolvent added. Additionally, nanoscale depressions on electrospun fibers were observed to change with dimethyl sulfoxide (DMSO) concentration in the PLLA/chloroform solution. A nonlinear relationship was found between the concentration of DMSO and the number and size of nanotopographical features. The surface depressions did not alter the hydrophobicity of the scaffold or degradation of the scaffold over a two-day period. To determine if fiber nanotopography altered cell behavior, macrophages (RAW 264.7 cells) were cultured on fibers with a smooth nanotopography or fibers with nanoscale depressions. RAW 264.7 cells spread less on fibers with nanoscale depressions than fibers with a smooth topography (p<0.05), but there were no differences between groups with regard to cell metabolism or the number of adherent cells. The results of this study demonstrate the necessity to consider the nanotopography of individual fibers as these features may affect cellular behavior. More importantly, we demonstrate a versatile method of controlling electrospun fiber nanotopography.

Electrospinning is the process by which a scaffold containing micrometer and nanometer diameter fibers are drawn from a polymer solution or melt using a large voltage gradient between a polymer emitting source and a grounded collector. Ramakrishna and colleagues first investigated electrospun fibers for neural applications in 2004. After this initial study, electrospun fibers are increasingly investigated for neural tissue engineering applications. Electrospun fibers robustly support axonal regeneration within in vivo rodent models of spinal cord injury. These findings suggest the possibility of their eventual use within patients. Indeed, both spinal cord and peripheral nervous system regeneration research over the last several years shows that physical guidance cues induce recovery of limb, respiration, or bladder control in rodent models. Electrospun fibers may be an alternative to the peripheral nerve graft (PNG), because PNG autografts injure the patient and are limited in supply, and allografts risk host rejection. In addition, electrospun fibers can be engineered easily to confront new therapeutic challenges. Fibers can be modified to release therapies locally or can be physically modified to direct neural stem cell differentiation. This review summarizes the major findings and trends in the last decade of research, with a particular focus on spinal cord injury. This review also demonstrates how electrospun fibers can be used to study the central nervous system in vitro.

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Higher order tasks in development for brain-computer interfacing applications require the invasiveness of intracortical microelectrodes. Unfortunately, the resulting inflammatory response contributes to the decline of detectable neural signal. The major components of the neuroinflammatory response to microelectrodes have been well-documented with histological imaging, leading to the identification of broad pathways of interest for its inhibition such as oxidative stress and innate immunity. To understand how to mitigate the neuroinflammatory response, a more precise understanding is required. Advancements in genotyping have led the development of new tools for developing temporal gene expression profiles. Therefore, we have meticulously characterized the gene expression profiles of the neuroinflammatory response to mice implanted with non-functional intracortical probes. A time course of differential acute expression of genes of the innate immune response were compared to naïve sham mice, identifying significant changes following implantation. Differential gene expression analysis revealed 22 genes that could inform future therapeutic targets. Particular emphasis is placed on the *