Silicon microelectrode array technology holds considerable promise in advancing the goal of developing stable, electrode-brain interfaces. Chronic unit recordings from multiple neurons in the brain would significantly enhance our understanding of normal physiology and provide a valuable control signal for use in neuro-prosthetic devices. However, the current generation of silicon microelectrodes does not allow stable long-term recordings. The precise mechanisms that cause failure of silicon microelectrode mediated recordings are not known. We hypothesize that the million-fold stiffness mismatch between silicon and neural tissues generates shearing forces at the interface resulting in an astro-glial scar formation that progressively excludes neurons from the vicinity of the recording electrodes. To test our hypothesis, we propose novel and innovative methods to a) determine the strain-sensitivity of primary astrocytes in terms of their adopting a scarring phenotype; b) determine if strain-induced scar formation around Si-microelectrodes degrades their recording capabilities in organotypic hippocampal slice cultures; and c) design coatings for Si-microelectrodes that allow the sustained local release of anti-inflammatory agents to decrease scarring and increase recording stability. The above aims represent a highly inter-disciplinary investigation of an important problem in the design and development of stable neuro-prosthetic devices. Successful completion of our research goals is likely to impact the mechanical and biochemical aspects of the design of the next generation of silicon microelectrode arrays, and subsequently significantly impact the quality of life of persons with disabilities.