ABSTRACT
Peripheral nerve injury (PNI) interferes with the quality of life of individuals by leading to life-long disturbances of function, and in some instances to the development of neuropathic pain. The functional consequences of PNI depend on the severity and type of the injury (for a recent review see Deumens et al. 2010). Nerve crush injuries have a generally good prognosis because the architecture of the peripheral nerve extracellular matrix (ECM), including the basal lamina tubes, remains largely intact. The Schwann cell-fi lled basal lamina tubes (or endoneurial tubes) of the Wallerian-degenerated distal nerve stump provide the orientational cues responsible for guiding regenerating axons to their original targets, allowing re-innervation and functional recovery (Fig. 1). The consequences of peripheral nerve transection are somewhat more complicated, depending on the severity and extent of ECM disruption. As with crush-type injuries, successful tissue repair demands that regenerating axons enter appropriate (or the original) endoneurial tubes to re-establish functional connectivity. Simple transection-type injuries may be repaired surgically by end-to-end tension-free sutures which bring the proximal and distal nerve stumps together and maintain the continuity of the original fascicular pattern within the damaged nerve. Transection-type injuries that result in larger gaps, however, require the bridging of the defect by an axon-growth promoting implant. The current gold-standard for such intervention is the nerve autograft: the harvesting of sensory nerves from the patients themselves, to provide a bridging material with optimal cellular and molecular constituents (i.e., growth factors, cell adhesion molecules and ECM molecules) for regeneration and
repair. In such situations, even if regenerating axons are able to bridge the gap and penetrate the distal nerve stump, other confounding issues, such as inappropriate target innervation and polyneuronal innervation of motor end-plates contribute to a reduced effi ciency of repair (Fig. 1). Thus only 40-50% of patients receiving autografts show functional benefi ts (for review, see Deumens et al. 2010). Furthermore, the autograft strategy presents numerous drawbacks:
(i) need for additional surgery to harvest the donor nerve, (ii) limited availability of transplant material, (iii) loss of function at the donor site, (iv) risk of painful neuroma formation at the donor site (Fig. 1).
