||The Utah Electrode Array (UEA) is a brain-implanted microelectrode recording device that has shown promise to assist patients with motor-control disabilities. Unfortunately, the UEA suffers from a foreign body response (FBR) that results in device movement away from implantation target, encapsulation of devices in meningeal origin tissue, loss of cortical tissue, and persistent neuroinflammation in the brain. These issues affect device functionality, and thus biocompatibility, and hinder widespread implementation of this technology. This dissertation examines whether device anchoring or extracellular matrix (ECM)-based device coating strategies can influence the biocompatibility of chronically implanted UEAs in the rat cortex. Results show that unanchored UEAs have a reduced FBR in comparison to those anchored to the skull, but also suffer from device movement as a result of cortical tissue remodeling, likely attributable to implantation-associated injury. To address implantation-associated injury, ECM was explored as a surface adsorbed device coating and was shown to be both hemostatic and immunomodulatory with in vitro assays. An apparatus was developed to coat Avitene™, an FDA-approved neurosurgical hemostatic ECM, onto the complex surface geometry of the UEA. Compared to uncoated control devices in a chronic rat model, Avitene™ coated devices experienced an enhanced FBR characterized by larger lesion cavities, enhanced meningeal encapsulation, and increased neuroinflammation, attributed to a higher degree of proinflammatory macrophages found surrounding the device coating. These result imply that future ECM-based coatings should include immunomodulatory components that address device-adherent macrophage activation state. Critical improvements in device anchoring and modulation of the FBR are still necessary to improve the biocompatibility of the UEA. Reducing the prevalence of FBR-related device failure is a necessary step that will require further attention before patients can benefit from this technology.