The development of a biologically active polymer coating that promotes the formation of a functionally enhanced and chronically stable nerve-electrode interface for recording and stimulation electrodes used in the central nervous system is proposed. The polymer will contain both cell adhesion and proteolytically degradable peptides with nerve growth factor (NGF) added as a slowly releasable neurotrophin to promote extension of neural processes to the electrode surface. Plasmin produced at the growth cones of neurites approaching the electrode will degrade the polymer matrix by hydrolysis of the target peptides. This degradation will enhance release of NGF and open the polymer at the active site of the electrode to preserve the low-impedance properties of the electrode surface and ensure that electrode function is not impaired by the polymer. The close proximity of the electrode surface to viable neural processes should enhance the stability and sensitivity of neural recording and may reduce charge-injection thresholds for neural excitation. The polymer coatings are intended for use with low impedance electrode materials such as iridium oxide and titanium nitride, as well as conventional noble metal electrodes. The Phase I aims are to develop methods for polymer synthesis, quantify NGF elution rates, assess the effects of the polymer on the relevant electrochemical properties of electrodes, evaluate the effects of plasmin on polymer degradation, and assess the effects of NGF elution by quantifying the response of PC12 ceils in a culture containing a NGF-eluting bolus of the polymer. A Phase II program would test the benefits of the polymer in an appropriate animal model. Intended applications of the polymer are in neural prostheses being developed as assistive devices for patients with neurodegenerative disorders such as ALS and locked-in syndrome, for rehabilitation in spinal cord injury and stroke, and for treatment of diseaserelated sensory deficits. Electrical stimulation-based therapies for the treatment of tremor, Parkinsons disease, and epilepsy also represent potential applications.
