Summary Artificial and non-artificial nerve grafts are the gold standard in peripheral nerve reconstruction in cases with extensive loss of nerve tissue, particularly where a direct end-to-end suture or an autologous nerve graft is inauspicious. Different materials are marketed and approved by the US Food and Drug Administration (FDA) for peripheral nerve graft reconstruction. The most frequently used materials are collagen and poly(DL-lactide-ε-caprolactone). Only one human nerve allograft is listed for peripheral nerve reconstruction by the FDA. All marketed nerve grafts are able to demonstrate sufficient nerve regeneration over small distances not exceeding 3.0 cm. A key question in the field is whether nerve reconstruction on large defect lengths extending 4.0 cm or more is possible. This review gives a summary of current clinical and experimental approaches in peripheral nerve surgery using artificial and non-artificial nerve grafts in short and long distance nerve defects. Strategies to extend nerve graft lengths for long nerve defects, such as enhancing axonal regeneration, include the additional application of Schwann cells, mesenchymal stem cells or supporting co-factors like growth factors on defect sizes between 4.0 and 8.0 cm.

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Nerve reconstruction of extended nerve defect injuries still remains challenging with respect to therapeutic options. The gold standard in nerve surgery is the autologous nerve graft. Due to the limitation of adequate donor nerves, surgical alternatives are needed. Nerve grafts made out of either natural or artificial materials represent this alternative. Several biomaterials are being explored and preclinical and clinical applications are ongoing. Unfortunately, nerve conduits with successful enhancement of axonal regeneration for nerve defects measuring over 4.0 cm are sparse and no conduits are available for nerve defects extending to 10.0 cm. In this study, spider silk nerve conduits seeded with Schwann cells were investigated for in vitro regeneration on defects measuring 4.0 cm, 10.0 cm and 15.0 cm in length. Schwann cells (SCs) were isolated, cultured and purified. Cell purity was determined by immunofluorescence. Nerve grafts were constructed out of spider silk from Nephila edulis and decellularized ovine vessels. Finally, spider silk implants were seeded with purified Schwann cells. Cell attachment was observed within the first hour. After 7 and 21 days of culture, immunofluorescence for viability and determination of Schwann cell proliferation and migration throughout the conduits was performed. Analyses revealed that SCs maintained viable (>95%) throughout the conduits independent of construct length. SC proliferation on the spider silk was determined from day 7 to day 21 with a proliferation index of 49.42% arithmetically averaged over all conduits. This indicates that spider silk nerve conduits represent a favorable environment for SC attachment, proliferation and distribution over a distance of least 15.0 cm in vitro. Thus spider silk nerve implants are a highly adequate biomaterial for nerve reconstruction.

Regardless of the nerve defect length, nerve injury is a debilitating condition for the affected patient that results in loss of sensory and motor function. These functional impairments can have a profound impact on the patient’s quality of life. Surgical approaches for the treatment of short segment nerve defects are well-established. Autologous nerve transplantation, considered the gold standard, and the use of artificial nerve grafts are safe and successful procedures for short segment nerve defect reconstruction. Long segment nerve defects which extend 3.0 cm or more are more problematic for repair. Methods for reconstruction of long defects are limited. Artificial nerve grafts often fail to regenerate and autologous nerve grafts are limited in length and number. Cadaveric processed/unprocessed nerve allografts are a promising alternative in nerve surgery. This review gives a systematic overview on pre-clinical and clinical approaches in nerve allograft transplantation.

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