Optical Stimulation and Monitoring of the Peripheral Nervous System: Perspectives and Challenges Toward Clinical Translation

Restoring sensory feedback in individuals with limb amputation requires the development of neural interfaces able to effectively control the activation of the Peripheral Nervous System (PNS). Conventional stimulation approaches based on electrodes suffer from several limitations such as limited spatial specificity, interference with nearby recordings, and fibrous tissue encapsulation. Optical neuromodulation offers a viable alternative that allows high-resolution peripheral nerve stimulation without the need for physical contact and without requiring any genetic modification. Infrared (IR) light can directly stimulate neurons through localized transient heating, while visible to near-IR (NIR) light can activate neurons indirectly via biointerfaces and nanotransducers that enhance selectivity and cell-specific targeting. In addition to stimulation, optical methods are also used for real-time and high-resolution monitoring of neural activity. This work is an all-around overview of optical stimulation and recording technologies developed in recent years for the PNS, highlighting their mechanisms of action and technological implementations, with a focus on their clinical translation. Overall, optical neural interfaces may expand the capabilities of neuromodulation beyond the limits of traditional electrical approaches, offering potential not only for precise sensory restoration, but also for neural rehabilitation and treatment of both neurological and cardiac disorders.