Neural interface technologies are increasingly evolving towards bio-inspired approaches to enhance integration and long-term functionality. Recent strategies merge soft materials with tissue engineering to realize biologically-active and/or cell-containing living layers at the tissue-device interface that enable seamless biointegration and novel cell-mediated therapeutic opportunities. This review maps the field of bio-inspired electronics and discusses key recent developments in tissue-like and regenerative bioelectronics, from soft biomaterials and surface-functionalized bioactive coatings to cell-containing ‘biohybrid’ and ‘all-living’ interfaces. We define and contextualize key terminology in this emerging field and highlight how biological and living components can bridge the gap to clinical translation.

The ability to modulate cellular electrophysiology is fundamental to the investigation of development, function, and disease. Currently, there is a need for remote, nongenetic, light-induced control of cellular activity in two-dimensional (2D) and three-dimensional (3D) platforms. Here, we report a breakthrough hybrid nanomaterial for remote, nongenetic, photothermal stimulation of 2D and 3D neural cellular systems. We combine one-dimensional (1D) nanowires (NWs) and 2D graphene flakes grown out-of-plane for highly controlled photothermal stimulation at subcellular precision without the need for genetic modification, with laser energies lower than a hundred nanojoules, one to two orders of magnitude lower than Au-, C-, and Si-based nanomaterials. Photothermal stimulation using NW-templated 3D fuzzy graphene (NT-3DFG) is flexible due to its broadband absorption and does not generate cellular stress. Therefore, it serves as a powerful toolset for studies of cell signaling within and between tissues and can enable therapeutic interventions.

Understanding cellular electrical communications in both health and disease necessitates precise subcellular electrophysiological modulation. Nanomaterial-assisted photothermal stimulation was demonstrated to modulate cellular activity with high spatiotemporal resolution. Ideal candidates for such an application are expected to have high absorbance at the near-infrared window, high photothermal conversion efficiency, and straightforward scale-up of production to allow future translation. Here, we demonstrate two-dimensional Ti₃C₂T_x (MXene) as an outstanding candidate for remote, nongenetic, optical modulation of neuronal electrical activity with high spatiotemporal resolution. Ti₃C₂T_x’s photothermal response measured at the single-flake level resulted in local temperature rises of 2.31 ± 0.03 and 3.30 ± 0.02 K for 635 and 808 nm laser pulses (1 ms, 10 mW), respectively. Dorsal root ganglion (DRG) neurons incubated with Ti₃C₂T_x film (25 μg/cm²) or Ti₃C₂T_x flake dispersion (100 μg/mL) for 6 days did not show a detectable influence on cellular viability, indicating that Ti₃C₂T_x is noncytotoxic. DRG neurons were photothermally stimulated using Ti₃C₂T_x films and flakes with as low as tens of microjoules per pulse incident energy (635 nm, 2 μJ for film, 18 μJ for flake) with subcellular targeting resolution. Ti₃C₂T_x’s straightforward and large-scale synthesis allows translation of the reported photothermal stimulation approach in multiple scales, thus presenting a powerful tool for modulating electrophysiology from single-cell to additive manufacturing of engineered tissues.

Fuzzy graphene and cellular optoporation enable intracellular recordings of cardiac action potentials on microelectrode arrays.