Nerve guidance channels are limited by lack of topographical guidance: Treatment of sizeable nerve gaps remains problematic following peripheral nerve injury. Functional outcomes are good when neurorrhaphy, or direct end-to-end… Click to show full abstract
Nerve guidance channels are limited by lack of topographical guidance: Treatment of sizeable nerve gaps remains problematic following peripheral nerve injury. Functional outcomes are good when neurorrhaphy, or direct end-to-end suture repair, is possible. The problem arises when there is significant segmental loss, which can occur following trauma as well as oncological procedures. In such scenarios, it is often not possible to appose severed nerve ends without causing significant tension. The current gold standard for management is to utilize autologous nerve grafts, commonly obtained from the sural nerve, to bridge these defects. This inevitably results in loss of cutaneous sensation over the lower limb, and the risk of donor site morbidities including infection and scarring. Suitable donor nerves remain finite in supply, and are often not ideally matched with recipient sites in terms of calibre and length. Nerve guidance channels have been designed to address these limitations, with proximal and distal nerve stumps telescoped and sutured to the ends of the artificial conduit during operative repair. Design objectives of nerve guidance channels have evolved over time with the emergence of new materials (Gaudin et al., 2016). Silicone represents a first-generation channel utilized to restore continuity and to prevent fibrous ingrowth from surrounding tissues. In being non-resorbable, silicone tubes frequently had to be removed as they caused extrinsic compression, offsetting their usefulness despite promising functional recovery. Thus, second-generation conduits shifted towards usage of biodegradable materials. These include commercially available products composed of collagen (Neuragen, Neuroflex, NeuroMatrix), polyglycolic acid (Neurotube), polylactide-caprolactone (Neurolac) and polyvinylalcohol-based hydrogel (SaluTunnel). It is essential that the next generation of guidance channels can facilitate repair across larger nerve gaps, with 2 cm representing a critical threshold beyond which the performance of artificial conduits remains fair. The present generation of nerve guidance channels are lacking in microstructure to provide physical guidance of the regenerative process. Provision of nanotopography within the channel lumen serves to minimize aberrant sprouting, and potentially enhance regeneration along the intended axis. Electrospinning is a means of generating aligned nanofibers to mimic the nerve microstructure and thus guide axonal growth and cellular migration within nerve guidance channels. Here, we emphasise how determination of appropriate physical and biological properties of the nanofiber scaffold can optimize neural regeneration, and in doing so, contribute towards design of a new generation of nerve guidance channels.
               
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