Toward guiding principles for the design of biologically-integrated electrodes for the central nervous system.

Innovation in electrode design has produced a myriad of new and creative strategies for interfacing the nervous system with softer, less invasive, more broadly distributed sites with high spatial resolution. However, despite rapid growth in the use of implanted electrode arrays in research and clinical applications, there are no broadly accepted guiding principles for the design of biocompatible chronic recording interfaces in the central nervous system (CNS). Studies suggest that the architecture and flexibility of devices play important roles in determining effective tissue integration: device feature dimensions (varying from 'sub'- to 'supra'-cellular scales, <10 µm to  >100 µm), Young's modulus, and bending modulus have all been identified as key features of design. However, critical knowledge gaps remain in the field with respect to the underlying motivation for these designs: (1) a systematic study of the relationship between device design features (materials, architecture, flexibility), biointegration, and signal quality needs to be performed, including controls for interaction effects between design features, (2) benchmarks for success need to be determined (biological integration, recording performance, longevity, stability), and (3) user results, particularly those that champion a specific design or electrode modification, need to be replicated across laboratories. Finally, the ancillary effects of factors such as tethering, site impedance and insertion method need to be considered. Here, we briefly review observations to-date of device design effects on tissue integration and performance, and then highlight the need for comprehensive and systematic testing of these effects moving forward.