Peripheral Nerve Nanoimaging: Monitoring Treatment and Regeneration.

Accidental and iatrogenic trauma are major causes of peripheral nerve injury. Healing after nerve injury is complex and often incomplete, which can lead to acute or chronic pain and functional impairment. Current assessment methods for nerve regeneration lack sensitivity and objectivity. There is a need for reliable and reproducible, noninvasive strategies with adequate spatial and temporal resolution for longitudinal evaluation of degeneration or regeneration after injury/treatment. Methods for noninvasive monitoring of the efficacy and effectiveness of neurotherapeutics in nerve regeneration or of neuropathic pain are needed to ensure adequacy and responsiveness to management, especially given the large variability in the patient populations, etiologies, and complexity of nerve injuries. Surrogate biomarkers are needed with positive predictive correlation for the dynamics and kinetics of neuroregeneration. They can provide direct real-time insight into the efficacy and mechanisms of individualized therapeutic intervention. Here, we review the state-of-the-art tools, technologies, and therapies in peripheral nerve injury and regeneration as well as provide perspectives for the future. We present compelling evidence that advancements in nanomedicine and innovation in nanotechnology such as nanotheranostics hold groundbreaking potential as paradigm shifts in noninvasive peripheral nerve imaging and drug delivery. Nanotechnology, which revolutionized molecular imaging in cancer and inflammatory disease, can be used to delineate dynamic molecular imaging signatures of neuroinflammation and neuroregeneration while simultaneously monitoring cellular or tissue response to drug therapy. We believe that current clinical successes of nanotechnology can and should be adopted and adapted to the science of peripheral nerve injury and regeneration.