ABSTRACT
Autologous nerve grafting is the current gold standard treatment for peripheral nerve injury in cases where direct suturing of nerve ends is not possible. Even though the functional restoration achieved by the autograft is not optimal, autologous nerve tissues still show higher regenerative capability than several synthetic conduits available in the clinical setting, the latter used only for gaps that do not exceed 3 cm in length. The aim of this chapter is to highlight how bio-mimicry, inspired by nerve development, structure, and spontaneous regeneration following mild nerve injury, can help in the design of synthetic templates with optimized bioactivity for nerve regeneration. 8.1 IntroductionThe peripheral nervous system is an extensive network of nerve fibers encompassing the entire body outside of the brain and
spinal cord, which enables the transmission of sensory and motor signals to and from the brain. Understanding the formation of this network during development, the structural organization of the fully mature tissue, and the spontaneous regeneration that occurs following limited nerve damage, provides valuable insight into strategies for facilitating restoration of peripheral nerve structure and function following extensive nerve injury.Although peripheral nerves have the capacity to regenerate following injury, this capacity is only present in cases for which the nerve is not completely severed and continuity of the connective tissue of the nerve is at least partially maintained. In cases of complete severing of the nerve, surgical tension-free suturing is required, or when tension-free suturing is not possible, a bridging method between the nerve stumps is needed for reinnervation of the distal nerve segment to occur. The current best approach to bridging nerve gaps is the use of a nerve autograft, containing viable Schwann cells and an intact nerve structure. However, even when a nerve autograft is available, the functional outcome of the repaired nerve is often significantly lacking. As such, many alternative bridging techniques have been and continue to be explored including the use of muscle and vein autografts, and many different types of natural and synthetic materials in the form of tubular and cylindrical structures. Although many of these techniques have shown promise in their ability to facilitate nerve regeneration, none have yet been able to surpass the efficacy of the nerve autograft. However, identification and optimization of key structural and biochemical properties of engineered constructs for nerve regeneration have the potential to greatly enhance the efficacy of these devices. To this aim, the design and the optimization of scaffolds for nerve regeneration are inspired by Nature, with focus on the formation of the peripheral nervous system during embryonic and fetal development, the structural organization of the fully mature tissue, and the spontaneous regeneration that occurs following minor nerve damage-specifically considering the roles and interdependence of the four main cell types in nerve: neurons (axons), Schwann cells, endothelial cells, and fibroblasts. Additionally, understanding how to modulate the body’s default response to tissue damage-to rapidly perform wound closure by scar formation and tissue contraction-is necessary to direct a regenerative response
leading to restoration of function, rather than tissue repair through fibrous scar formation.
