Neural interfaces are the core of prosthetic devices, such as implantable stimulating electrodes or brain–machine interfaces, and are increasingly designed for assisting rehabilitation and for promoting neural plasticity. Thus, beyond the classical neuroprosthetic concept of stimulating and/or recording devices, modern technology is pursuing toward ideal bio/electrode interfaces with improved adaptability to the brain tissue. Advances in material research are crucial in these efforts and new developments are drawing from engineering and neural interface technologies. Here, a microporous, self‐standing, 3D interface made of polydimethylsiloxane (PDMS) implemented at the interfacing surfaces with novel conductive nanotopographies (carbon nanotubes) is exploited. The scaffold porosity is characterized by 3D X‐ray microtomography. These structures are used to interface axons regenerated from cultured spinal explants and it is shown that engineering PDMS 3D interfaces with carbon nanotubes effectively changes the efficacy of regenerating fibers to target and reconnect segregated explant pairs. An improved electrophysiological performance is shown when the spinal tissue is interfaced to PDMS enriched by carbon nanotubes that may favor the use of our substrates as regenerative interfaces. The materials are implanted in the rat brain and a limited tissue reaction surrounding the implants at 2, 4, and 8 weeks from surgery is reported.
