Soft bioelectronic technologies for selective and multimodal peripheral nerve interfaces
The peripheral nervous system (PNS) regulates the exchange of sensory information and
motor commands between the body and the central nervous system. Further, through the
autonomic nervous system, the PNS plays a pivotal role in controlling vital physiological
processes. For treating various PNS-related and non-neurological conditions, neurotechnologies
interfacing with the PNS are critical. Yet, precisely stimulating or inhibiting target
fibers remains a significant challenge due to the complex morphology and composition of
nerves. Traditional peripheral nerve interfaces, relying on electrical stimulation, grapple with
a problematic tradeoff between selectivity and invasiveness. Extraneural cuff electrodes are
considered the safest yet least selective. Cuffs present other issues too, like lead migration,
fracture, infection, and nerve injury, often due to inadequate sizing and use of rigid/compressive
materials.
This thesis introduces an approach to tackle these obstacles through the development of a soft
peripheral nerve interface. The system's translational potential was experimentally validated
in small and large animal models. Moreover, the interface was designed to incorporate optical
stimulation functionality, allowing for advanced selective stimulation strategies.
The first part of the work centers on the development of a soft, adaptable cuff electrode. Using
a 150 µm silicone layer (E~1 MPa) as the base material, and incorporating stretchable thin-film
gold tracks, the cuff was designed to adapt to a range of nerve sizes and shapes. It features a
unique belt-like structure, ensuring near-complete perimeter coverage and facilitating implantation.
Electrochemical characterization and rat sciatic nerve testing confirmed the device's
stable performance across varying conditions. The cuff's applicability was further demonstrated
in translational applications involving pig sciatic nerve stimulation and vagus nerve
recording. The 16-channel stimulating cuff demonstrated the ability to selectively activate up
to five muscles, with comparable and improved performances to existing systems.
Additionally, integration of rigid light sources within a soft cuff for opto-modulation was
explored. Despite initial challenges related to strain gradients in soft-rigid systems, the developed
cuff maintained conformability and LED functionality while stretching (~ 35% strain).
As a proof-of-concept, spatially distinct stimulation of sciatic nerve from four separate sites was demonstrated, indicating potential for high-density, stretchable optoelectronic interfaces.
Lastly, nerve-on-a-chip systems were leveraged ex vivo to explore novel peripheral neuromodulation
strategies. These platforms, which amplify and track propagating action potentials
from explanted nerve rootlets, hold great promise for elucidating the complex mechanisms
behind ultrasonic and optical stimulation techniques, and for optimizing strategies before in
vivo validation.
In conclusion, this work contributes to simplifying the implantation procedure of cuffs, enabling
intimate contact with varying nerve sizes, achieving remarkable selectivity even in
complex fascicular organization and providing an improved chronic (6-week) biointegration.
Furthermore, the integration of optical stimulation and the development of ex vivo testing
strategies propels the optimization and characterization of novel modulation methods, thus
enhancing our understanding of peripheral neural mechanisms.
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