Nanoparticle and Biomolecule Surface Modification Synergistically Increases Neural Electrode Recording Yield and Minimizes Inflammatory Host Response

Due to their ability to interface with neural tissues, neural electrodes are the key tool used for neurophysiological studies, electrochemical detection, brain computer interfacing, and countless neuromodulation therapies and diagnostic procedures. However, the long-term applications of neural electrodes are limited by the inflammatory host tissue response, decreasing detectable electrical signals, and insulating the device from the native environment. Surface modification methods are proposed to limit these detrimental responses but each has their own limitations. Here, a combinatorial approach is presented toward creating a stable interface between the electrode and host tissues. First, a thiolated nanoparticle (TNP) coating is utilized to increase the surface area and roughness. Next, the neural adhesion molecule L1 is immobilized to the nanoparticle modified substrate. In vitro, the combined nanotopographical and bioactive modifications (TNP+L1) elevate the bioactivity of L1, which is maintained for 28 d. In vivo, TNP+L1 modification improves the recording performance of the neural electrode arrays compared to TNP or L1 modification alone. Postmortem histology reveals greater neural cell density around the TNP+L1 coating while eliminating any inflammatory microglial encapsulation after 4 weeks. These results demonstrate that nanotopographical and bioactive modifications synergistically produce a seamless neural tissue interface for chronic neural implants.