The Hybrid Retinal Implant (HRI) is a subretinal biohybrid neural interface that integrates a high-density 3D microelectrode array with micro-well-like structures embedded with photoreceptor precursors (PRPs)-glutamatergic neurons derived from human embryonic stem cells (hESC-PRPs).

Each well, typically ~10-15µm in diameter (single-cell resolution) and 15-20µm height, is designed to confine the electric field around individual neurons by ensuring tight electrode-cell proximity, thereby increasing sealing resistance and reducing current leakage to adjacent pixels. This geometry minimizes electrical crosstalk and lowers neural activation thresholds toward the pico-coulomb range. Modeling predicts approximately a three orders of magnitude reduction, allowing electrodes to operate in an analog mode capable of stimulating individual cells. Such localized activation is hypothesized to preserve the natural organization and selectivity of retinal circuits and, when combined with a high-density electrode array, to significantly enhance the achievable spatial resolution of restored vision.

The fabrication process involves multilayer photolithography of SU-8 to form the 3D wells, metal deposition for electrode patterning, and biofunctionalization of the electrode surface with short extracellular-matrix (ECM) derived peptides (e.g., RGD and YIGSR) that mimic the physiological microenvironment of retinal cells and promote neuronal adhesion through integrin-mediated signaling.

Electrophysiological recordings demonstrated a marked reduction in stimulation thresholds and improved charge efficiency compared with planar electrodes, while histological and in-vivo analyses confirmed high neuronal viability, excellent anatomical integration in the subretinal space, axonal extension toward the bipolar cell layer with synaptic marker expression, and intimate embedding of neurons within the wells-together validating the HRI concept as a promising pathway toward high-acuity, cell-resolved vision restoration.

Device Specifications

• Number of electrodes: 3172
• Electrode diameter: 10 μm
• Electrode pitch: 13 μm