Using intracortical microelectrodes to record brain signals can provide valuable insight into brain functions and treatment plans for neurological disorders. However, microelectrode performance is significantly affected by the neuroinflammatory response following implantation largely resulting from blood-brain barrier damage and leaky constituents following implantation. Among these constituents, the role of penetrated microorganisms such as bacteria on neuroinflammation remains unclear. In contrast to other areas of the body, it is possible for the brain to respond to very low concentrations of bacteria that do not manifest as systemic infections but may induce neuroinflammatory response in the brain due to its higher sensitivity. Even with an appropriate sterilization, a very low level of bacteria can still migrate into the incision site or enter the brain from other internal sources such as the bloodstream throughout the implantation process. Indefinite delivery of systemic antibiotics has found to be ineffective in treating low levels of antibiotic-resistant bacteria, and can alter the composition and population of existing, stable strains of bacteria, that are symbiotic to human health. Thus, the development of a localized method to modulate bacteria levels may be a critical step towards reducing the neuroinflammatory response following microelectrode implantation. Our preliminary data show that neuroinflammatory responses to intracortical microelectrodes can be exacerbated by bacterial contamination (even at very low abundance); Systemic antibiotics resulted in decreased recording performance and increased neuroinflammatory response as a significantly more robust neuroinflammatory response than control was observed by 12 weeks of implantation. Also, live bacteria were found in the tissue adjacent the implants at 12 weeks post-implantation. Our preliminary data also showed that titania nanotube arrays (TNAs) prevented bacterial growth and maintained sustained local antibiotics delivery for >12 weeks. In this proposal, we aim to explore the antimicrobial properties of the TNA coatings in relation to their effect on bacterial populations and the neuroinflammatory response following intracortical probe implantation as well as investigate the potential outcomes of local versus systemic antibiotic delivery in controlling resistant bacteria. A pilot study using Neuronexus recording probes coated with TNAs on their backside will be performed to evaluate the mechanical integrity of TNA coatings in vivo as well as their effect on recording performance.