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Polylysine Modified Hydrogel Coatings to Enhance the Neuro-Electrode Interface

Shreyas Rao, Chemical and Biomolecular Engineering, the Ohio State University, 140 W 19th Ave, Columbus, OH 43210, Michael Owens, Chemical and Biomolecular Engineering, Ohio State University, 140 W 19th Ave, Columbus, OH 43210, and Jessica O. Winter, Chemical and Biomolecular Engineering/Biomedical Engineering, Ohio State Unversity, 140 W 19th Ave, Columbus, OH 43210.

Neural prostheses have significantly advanced treatment options for patients with traumatic injury or neurodegenerative disease. Prostheses typically consist of a signaling unit, which creates an electrical response to an external stimulus (e.g., light, sound, input from sensory nerves). This signal is then passed to an electrode array that replaces the function of missing or damaged nerves by providing the signal to remaining neural circuitry. One of the major limitations of these devices has been the inability to integrate electrode arrays with target neural tissue. Poor interfacing can result in incompatibilities of the electrode material, anatomical changes resulting from disease or injury progression, and the trauma of prosthetic implantation.

Our research is focused on improving electrode-host integration by applying tissue engineering strategies to prosthetic devices. To this end, we have developed electrode coatings consisting of hydrogels, cross-linked, hydrophilic, swollen polymers. Hydrogels make excellent brain mimetics because of their structural and mechanical similarity to glycosaminoglycans, which make up brain connective tissue. However, because of their synthetic nature, polymeric hydrogels often do not support cell adhesion. Our previous research efforts identified polylysine as a potential biomolecule to enhance neuron adhesion, extension, and regeneration at the biomaterial interface. Here we describe our efforts to incorporate polylysine into polymeric poly (ethylene glycol) poly (caprolactone) (PEGPCL) hydrogels to enhance neurite extension.

PEGPCL hydrogels were synthesized as described previously [1,2] with modifications to enhance yield. Polylysine was conjugated to NHS-PEG-Acrylate through standard NHS bioconjugation methods producing a polylysine-PEG-acrylate compound, which could be incorporated into hydrogels through UV photopolymerization. The yield of polylysine conjugation was characterized using FITC-conjugated polylysine and quantified with a fluorescent plate reader. We are currently assessing the cell response to these materials using PC12 cells and primary rat cortical neurons. In particular, we are evaluating neuronal adhesion (cells/micron^2) and neurite extension produced for different levels of polylysine conjugation versus unconjugated control hydrogels. The coating described here could be used to enhance the electrode-host interface, possibly lowering electrical requirements for stimulation which will improve prosthesis resolution and size.

1. Sawhney AS, Pathak CP, Hubbell JA. Bioerodible Hydrogels Based on Photopolymerized Poly(Ethylene Glycol)-Co-Poly(Alpha-Hydroxy Acid) Diacrylate Macromers. Macromolecules 1993;26(4):581-587.

2. Winter JO, Cogan SF, Rizzo III JF. Neurotrophin-Eluting Hydrogel Coatings for Neural Stimulating Electrodes. J Biomed Mater Res B 2007;81B(2):551-563.