Research Team: Chloé Bernardoni, Adrien Rapeaux, Ahmad Shah Idil, Timothy Constandinou (PI)
Collaborators: Rylie Green (Imperial College London), Molly Stevens (Oxford university)
Funding: Advanced Research and Innovation Agency (ARIA)
Background
Current neurotechnologies cannot precisely interface with the brain at the level of individual neural circuits. Deep brain stimulation, for example, activates broad tissue volumes and lacks the cell-type specificity needed to treat disorders that arise from the dysfunction of specific neuronal populations — such as Alzheimer's or Parkinson's disease.
RESCUE aims to overcome this limitation by developing a new class of biohybrid neurotechnology that fuses engineered biology with implantable hardware to restore neural circuits impaired by trauma or disease. The platform integrates three complementary technologies:
- Injectable electroconductive hydrogels (SAP-ECHs) — self-assembling peptide scaffolds that form biomimetic, bio-instructive structures in situ within deep-brain regions.
- Optically responsive neural progenitor cells (NPCs) — human stem-cell-derived neurons rendered light-sensitive through semiconducting polymer nanoparticles (SPNs), avoiding the need for genetic modification.
- A fully implantable optical stimulation system — a wirelessly powered device delivering multi-wavelength light through a flexible polyamide micro-cable, enabling independent modulation of distinct neuronal populations at depth.
Together, these components form addressable biohybrid assemblies that can be modulated with targeted cell-type specificity (>95%), unlocking new therapeutic avenues for neurodegenerative disease.
Our approach
The NGNI lab leads the development of the implantable electronics and optical stimulation system (EOS) that drives the biohybrid platform. Our work spans:
- Design of an ultralow-power, wirelessly powered implantable device integrating a custom LED driver, power management, and RF telemetry.
- Development of a miniaturised, deep-brain light delivery method built around a flexible polyimide cable carrying µLEDs for on-site optical stimulation.
- On-chip temperature sensing to prevent tissue damage and ensure safe chronic operation.
- Firmware and system-level integration enabling programmable, multiplexed optical stimulation paradigms across four independent light channels.
This device is validated first in vitro and ex vivo, then integrated into the full biohybrid platform for in vivo assessment in rodent models of hippocampal circuit modulation.