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 neuro-prosthetic 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. We exploit here a micro-porous, self-standing, three-dimensional (3D) interface made of polydimethylsiloxane (PDMS) and implemented at the interfacing surfaces with novel conductive nano-topographies (carbon nanotubes). We characterize the scaffolds porosity by 3D X-ray micro-tomography. We use these structures to interface axons regenerated from cultured spinal explants and we show that engineering PDMS 3D interfaces with carbon nanotubes effectively changes the efficacy of regenerating fibers to target and re-connect segregated explant pairs. We show, when the spinal tissue is interfaced to PDMS enriched by carbon nanotubes, an improved electrophysiological performance that may favor the use of our substrates as regenerative interfaces. We implant the materials in the rat brain and we report a limited tissue reaction surrounding the implants at 2, 4 and 8 weeks from surgery.