Neurotrophin-Eluting Hydrogel Coatings for Neural Stimulating Electrodes Jessica O. Winter, 1,2 Stuart F. Cogan, 3 Joseph F. Rizzo III 1,4 1 Center for Innovative Visual Rehabilitation, Boston VA Hospital, Boston, Massachusetts 2 Department of Chemical and Biomolecular Engineering, Ohio State University, Columbus, Ohio 3 EIC Laboratories, Norwood, Massachusetts 4 Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts Received 10 May 2006; revised 7 July 2006; accepted 18 July 2006 Published online 13 October 2006 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jbm.b.30696 Abstract: Improved sensory and motor prostheses for the central nervous system will require large numbers of electrodes with low electrical thresholds for neural excitation. With the eventual goal of reducing stimulation thresholds, we have investigated the use of biodegradable, neurotrophin-eluting hydrogels (i.e., poly(ethylene glycol)-poly(lactic acid), PEGPLA) as a means of attracting neurites to the surface of stimulating electrodes. PEGPLA hydrogels with release rates ranging from 1.5 to 3 weeks were synthesized. These hydrogels were applied to multielectrode arrays with sputtered iridium oxide charge-injection sites. The coatings had little impact on the iridium oxide electrochemical properties, including charge storage capacity, impedance, and voltage transients during current pulsing. Additionally, we quantitatively examined the ability of neurotrophin-eluting, PEGPLA hydrogels to promote neurite extension in vitro using a PC12 cell culture model. Hydrogels released neurotrophin (nerve growth factor, NGF) for at least 1 week, with neurite extension near that of an NGF positive control and much higher than extension seen from sham, bovine serum albumin- releasing boluses, and a negative control. These results show that neurotrophin-eluting hydrogels can be applied to multielectrode arrays, and suggest a method to improve neuron- electrode proximity, which could result in lowered electrical stimulation thresholds. Reduced thresholds support the creation of smaller electrode structures and high density electrode prostheses, greatly enhancing prosthesis control and function. ' 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 81B: 551–563, 2007 Keywords: neural prostheses; hydrogel; NGF; nerve regeneration; electrical stimulation INTRODUCTION Every year, millions of people lose neural function as a result of traumatic injury (i.e., spinal cord injury), 1,2 congenital con- ditions, 3 degenerative diseases (e.g., retinitis pigmentosa or age-related macular degeneration), 4 or other neurological dis- orders. 1,2,5 Unfortunately, tissues of the central nervous sys- tem do not regenerate under normal conditions. 6 However, in many cases, portions of the neural pathway upstream from the defective site remain functionally intact, 1,7 and it is possi- ble to develop neural prostheses that utilize these pathways to restore lost function. 1,3,4,8,9 Simple neural prostheses requiring few numbers of elec- trodes 8–10 have enjoyed great success. However, the creation of multielectrode arrays with the high pixel densities neces- sary to treat more complicated deficits (e.g., vision loss, limb control) has been challenging. 7,11,12 Two limitations in achieving this goal are local tissue anatomy 7,11,12 and the formation of highly resistive scar tissue between the elec- trodes and target neurons. 13,14 Anatomical considerations frequently prevent prosthesis implantation in direct proxim- ity to the neurons of interest. Because stimulation efficiency declines with distance, 15–18 any increase in the separation from target neurons can markedly raise stimulation thresh- olds. Anatomical problems are confounded by the presence of encapsulating scar tissue, which forms during the immune response to some implant materials 2,7 and as a result of many degenerative diseases. 19 Scar tissue not only increases electrode-target separation distance, but also has a higher re- sistance than native tissue. 13 The combined effect of these Correspondence to: J. O. Winter (e-mail: winter.63@osu.edu) Contract grant sponsor: Department of Veterans Affairs, Rehabilitation Research and Development Service Contract grant sponsor: National Institutes of Health; contract grant number: R43 NS04968701 ' 2006 Wiley Periodicals, Inc. 551