A biohybrid bridge between brain and machine: Development and application of a neural implant using iPSC-derived neuronal membranes

Abstract

Despite the numerous advancements in electronics interfacing with the nervous system over the decades, a long-standing challenge has been to achieve long-term stability in vivo. The foreign body reaction (FBR), an internal inflammatory mechanism triggered upon implantation of foreign objects, is responsible for fibrotic encapsulation of implanted neural probes, leading to a gradual decline in device functionality due to the physical barrier it creates between electrodes and host tissue (at the tissue-electrode interface). However, the field has progressed from using rigid electronics to incorporating soft biomaterials that conform to the shape of our soft biology.

This thesis aimed to explore a novel solution to FBR in neural implants, proposing the hypothesis that the use of material derived from human-derived neurons themselves as a biological mediator, incorporated in the device design, would result in reduced inflammation and improved therapeutic efficacy and stability in vivo. To test this hypothesis, the project fused flexible electronics and bioengineering to extract and form human iPSC-derived neuronal membranes, which were then characterised and studied for their performance and electrophysical sealing properties in vitro. The study found that these neuronal membranes displayed high mobility and stability in vitro and had improved sealing properties compared to other native membranes. Furthermore, the study revealed that implants integrating neuronal membranes resulted in a reduction of inflammation 28 days post-implantation compared to those without, as confirmed by immunohistochemical analysis and successful electrophysiological recordings.

These results hold tremendous potential for the future of biocompatible neural interfaces and chronic therapeutic interventions, as they suggest the possibility of enhancing the signal-to-noise ratio and reducing impedance levels through meticulous manipulation and control of lipid and protein composition.