Abstract² Two methods for incorporating drug eluting coatings consisting of Matrigel (MG) loaded with dexamethasone (DEX) onto the Parylene sheath electrode (PSE) were developed and compared. The purpose of the coatings is to reduce the immune response evoked by tissue damage during electrode insertion into the cortex and subsequent sustained aggravation of tissues by the implant. Parylene surfaces are hydrophobic and repel MG, therefore, both physical and chemical methods were investigated to disrupt surface tension and increase surface energy to facilitate even coating onto the PSE. A gelling step was also investigated to improve loading of coating onto PSE. Spectrophotometry was used to measure the amount of DEX loaded onto the PSE. Loading of up to 563 ng of DEX was achieved by using a combination of surface energy modification and coating gelling, whereas sonication assisted coating methods loaded 205 ng. I. INTRODUCTION Intracortical electrodes serve an important role in the acquisition of extracellular electrical activity in order to better understand the function of the brain and drive prosthetic devices such as robotic limbs. A common approach is to fashion intracortical electrodes from rigid tines or planar shafts made from either metal, such as stainless steel or tungsten, or silicon, respectively [1]. Implantation of these electrodes induces an immediate immune response to the stab wound injury and a sustained response associated with continued aggravation by micromotion combined with mechanical mismatch of the electrodes with tissue. The immune response results in a glial scar around the electrode and neuronal retraction, which increases the distance between the neuron and recording site, raises the effective electrode impedance, and has been correlated to signal attenuation [2]. One strategy used to reduce inflammation around the electrode site and increase the signal to noise ratio of recordings is to coat neural electrodes in either adhesive molecules to stimulate attachment of cells to the surface of the array [3], immunosuppressants to reduce the immune response [4], or neurotrophic factors that support cell viability and encourage growth and differentiation of neurons towards the electrode [5]. * This work was sponsored by the Defense Advanced Research Projects Agency (DARPA) MTO under the auspices of Dr. Jack Judy through the Space and Naval Warfare Systems Center, Pacific Grant/Contract No. N66001-11-1-4207. C. Lee, L.Yu, J. T. W. Kuo, B. Kim, T. Hoang and E. Meng are with the Department of Biomedical Engineering at the University of Southern California, Los Angeles, CA 90089 USA (corresponding author: 213-740- 6952; e-mail: ellis.meng@usc.edu). Another strategy is to change the physical design of the neural electrode such as .HQQHG\¶V neurotrophic electrode (NE) and the Parylene Sheath Electrode (PSE) developed at the Biomedical Microsystems Lab. .HQQHG\¶s NE consists of a glass cone made from the tip of a patch clamping pipette with microwire electrodes²deinsulated at the tip²manually affixed to the inside of the cone [6]. .HQQHG\¶V 1( KDV EHHQ used to collect signals in human subjects for 5 years [7], but because the cone is assembled by hand out of glass, the flexibility of its design and scale of its production is limited. Initially, Kennedy threaded an autologous section of sciatic nerve through the cone to encourage neurons to grow into the cones, next to the electrodes [6], but later substituted the nerve with either Matrigel (MG), nerve growth factor, or a combination of the two [8]. MG is an extract from the Engelbreth-Holm-Swarm mouse sarcoma that is rich in extracellular matrix protein (adhesion molecules) such as laminin, collagen, and entactin, and contains growth factors such as epidermal, nerve, and fibroblast growth factors [9]. MG is routinely used in cell culturing to induce differentiation and produce realistic morphologies of cell structures in vitro and in vivo to deliver and support stem cells [10], and assay anti- angiogenesis drugs [11]. The PSE is similar in principle WR .HQQHG\¶V NE, consisting of a cone shaped sheath lined with electrodes on the inside and outside [12] (Fig. 1). However, the PSE is micromachined rather than handmade, which allows greater flexibility of design, including the shape of the sheath and number of electrodes, and is amenable to mass production. The PSE is manufactured from the biocompatible (USP Class VI) polymer Parylene (which is also used to coat other FDA approved implantable devices such as pacemakers, cochlear implants, and controllers for deep brain stimulation). The lower modulus of Parylene compared to metals, silicon, glass, and other polymers may reduce damage associated with micromotion, while the sheath structure accommodates neural tissue ingrowth towards electrode recording sites for improved chronic acquisition of neuronal signals. The thin film Pt electrodes are deposited on the Parylene surface; platinum is an inert metal commonly used as an electrode in neural interfaces and is biocompatible. This study presents and compares two methods used to coat the PSE with MG loaded with dexamethasone (DEX), a powerful immunosuppressant shown to reduce the immune response when administered intracranially [13]. MG was VHOHFWHG EHFDXVH RI LWV VXFFHVV LQ .HQQHG\¶V NE and its ability to cause neurons to differentiate in vitro and to ’UXJ (OXWLQJ &RDWLQJ IRU ’ 3DU\OHQH 6KHDWK (OHFWURGH Curtis Lee, Student Member, IEEE, Lawrence Yu, Jonathan T. W. Kuo, Brian Kim, Tuan Hoang, and Ellis Meng, Senior Member, IEEE 6th Annual International IEEE EMBS Conference on Neural Engineering San Diego, California, 6 - 8 November, 2013 978-1-4673-1969-0/13/$31.00 ©2013 IEEE 839