Intracortical brain-machine interfaces (BMIs) offer the promise of providing independence and an improved quality of life to individuals with severe motor dysfunction resulting from neurologic injury or disease. Despite hardware, software, and surgical advances for BMIs, neural spike activity recordings continue to show high variability and unpredictability and ultimately progressive degradation. A neuroinflammatory tissue response that results in astroglial scarring and neuronal process degradation surrounding the implants is widely regarded as a primary cause of neural recording signal variability and degradation. We propose to use a combination of approaches to mitigate the tissue response to improve neural recording quality and stability. Our Microfluidic/Eluting Neural Drug Delivery System (MENDDS) incorporates a mechanically-adaptive intracortical microelectrode implant with a novel microfluidic-aided eluting architecture. A microfluidic channel embedded within a permeable polymer nanocomposite runs down the length of the probe before U-turning and running back up to the back end of the probe. The contents of the channel diffuse through the polymer nanocomposite walls and out to tissue. Drug delivery directly at the implant site facilitates targeted control of local drug concentration without exposing distant tissue and organs to toxic drug levels. Microfluidic-aided elution allows the implant to distribute therapeutic agents uniformly around the implant. Advantageously, this system elutes anti-inflammatory agents along the length of the probe without suffering from the limited release duration of drug-eluting coatings. The key question this proposal will answer is: does local, chronic (>8 week) anti-oxidant elution from a mechanically-compliant implant inhibit the neuroinflammatory response, improve proximity of neuronal cell bodies near to recording microelectrodes, improve neural recording quality, and preserve functional outputs associated with the implanted region of the cortex? To provide insight into this question, we will first optimize resveratrol delivery profile through the MENDDS to maximize neural recording quality and minimize neuroinflammation and adverse local and peripheral effects. We will then quantify the impact of microfluidic-aided elution on chronic neuroinflammation and neural recording quality. Previous resveratrol-related studies have identified a wide therapeutic concentration range of 0 – 100 µM, while large doses of resveratrol that are regularly administered systemically have been associated with adverse side effects, including hemorrhaging. We endeavor to determine an optimal resveratrol concentration within this range for microfluidic-aided elution from the MENDDS. We will implant one MENDDS device into the primary motor cortex of 216 Sprague-Dawley rats across six concentration groups for either 1, 2, or 4 weeks. An osmotic pump will serve drive resveratrol solutions ranging from 0 - 100 µM through the MEN...