Nerve Repair Strategies

To repair severed nerves, the stump ends of the nerve fiber bundles can be surgically reconnected and sutured together. Transected tissue will generally not regenerate without surgical realignment (Wasielewski et al. 1992). A tissue transection, with additional tissue damage that creates a gap in the tissue, may not be a candidate for surgical reconnection if the reconnection will create tension in the nerve. Thus, large gaps must be repaired with a graft inserted between the proximal and distal nerve stumps as a guide for regenerating axons.

While the current gold standard of treatment is the use of an autologous sural nerve graft, there is a great deal of interest in the development of synthetic nerve guidance channels (NGC; Fig. 2) that perform equally well. Treatment of nerve fiber transections and small tissue gaps, has a high rate of success with both synthetic and autologous implants. However, as the tissue gap increases in length the probability of successful regeneration decreases dramatically (Yannas and Hill 2004). NGC technology is therefore of interest due to the potential inclusion of known stimuli which may allow regeneration of larger tissue gaps, and due to the complications associated with producing an autologous graft. The process of harvesting an autologous graft requires an additional surgical operation, may result in sensory complications at the donor site, and exposes the patient to increased surgical risks. The NGC is, in its most basic form, a hollow tube into which two severed ends of a nerve fiber bundle can be inserted and sutured into place. The implanted

Fig. 2 Illustration of a NGC bridging two severed ends of a transected nerve fiber bundle. Though no commercially available NGCs are fabricated from electrically-active materials, future developments in conductive or piezoelectric materials for NGC applications may accelerate axon growth between nerve stumps

NGC serves to protect and support regenerating tissue. The NGC assists the realignment of nerve tissue and maintains high levels of locally released growth factors by encapsulating the nerve.

While degradable polymer scaffolds without biologically-inspired nanoscale features are, to date, the standard NGC material choice, studies have investigated the efficacy of NGC materials with a wide variety of properties. Commercially available NGCs (Table 1), such as the NeurgaGen collagen tube (Integra LifeSciences, Plainsboro, New Jersey) and the hydrogel-based SaluBridge (SaluMedica, Atlanta, Georgia) are inert polymer tubes that do not incorporate the several neural growth stimulatory cues under active investigation (Meek and Coert 2008). Standard NGCs do incorporate desirable flexibility, which is an important element in NGC design due to the need to reduce tension and mechanical stress during nervous system tissue regeneration (Wasielewski et al. 1992). Also, biodegradation is considered to be an essential quality for NGC materials. As tissue regenerates, the scaffold will ideally degrade as it is replaced by healthy tissue. Failure of the scaffold to degrade could potentially constrict growing tissue and prevent proper regeneration. Also, degradable NGCs eliminate the need for a second operation for implant removal.

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