Managing surface energy dynamics for enhanced axonal growth: An overview of present and future challenges

To create functional neuronal circuit units during nervous system development and/or regeneration, axons are subjected to guidance signals. Expression of these signals occurs in spatiotemporal variations and is translated by the growth cone into a pathway to reach the connecting target which can be a neuron or a non-neuronal cell such as a muscle cell. This path is generated by interactions with the surrounding environment such as cells or the extracellular matrix, a complex molecular substrate. Understanding the interactions with this last component is essential to stimulate nerve regeneration in the context of motor peripheral nerve trauma, the most common source of disabilities, increasing with aging. The goal is to mimic its composition and specific characteristics using innovative biomaterials and/or implants. This review highlights some aspects of the recent findings in nerve repair. After an introduction to the peripheral nervous system, we present an overview of nerve degeneration and regeneration mechanisms before detailing the strategies used nowadays to optimize nerve (re)growth with a specific focus on the use of electric field. We discuss the advantages and limits of each option in terms of therapeutic applications.