Autografting is the gold standard in the repair of peripheral nerve injuries that are not amenable to end-to-end coaptation. However, because autografts result in donor-site defects and are a limited resource, an effective substitute would be valuable. In a rat model, we compared isografts with Integra NeuraGen (NG) nerve guides, which are a commercially available type I collagen conduit, with processed rat allografts comparable to AxoGen's Avance human decellularized allograft product. In a 14-mm sciatic nerve gap model, isograft was superior to processed allograft, which was in turn superior to NG conduit at 6 weeks postoperatively (P < 0.05 for number of myelinated fibers both at midgraft and distal to the graft). At 12 weeks, these differences were no longer apparent. In a 28-mm graft model, isografts again performed better than processed allografts at both 6 and 22 weeks; regeneration through the NG conduit was often insufficient for analysis in this long graft model. Functional tests confirmed the superiority of isografts, although processed allografts permitted successful reinnervation of distal targets not seen in the NG conduit groups. Processed allografts were inherently non-immunogenic and maintained some internal laminin structure. We conclude that, particularly in a long gap model, nerve graft alternatives fail to confer the regenerative advantages of an isograft. However, AxoGen processed allografts are superior to a currently available conduit-style nerve guide, the Integra NeuraGen. They provide an alternative for reconstruction of short nerve gaps where a conduit might otherwise be used.

Nerve conduits have emerged as alternatives to autologous nerve grafts, but their use in large-diameter nerve deficits remains untested. We report four patients who underwent repair of large-diameter nerves using absorbable nerve conduits and discuss the failed clinical outcomes. The reported cases demonstrate the importance of evaluating the length, diameter, and function of nerves undergoing conduit repair. In large-diameter nerves, the use of conduits should be carefully considered.

Background-Processed nerve allografts offer a promising alternative to nerve autografts in the surgical management of peripheral nerve injuries where short deficits exist.

A consensus on the optimal treatment of painful neuromas does not exist. Our objective was to identify available data and to examine the role of surgical technique on outcomes following surgical management of painful neuromas. In accordance with the PRISMA guidelines, we performed a comprehensive literature search to identify studies measuring the efficacy of the surgical treatment of painful neuromas in the extremities (excluding Morton's neuroma and compression neuropathies). Surgical treatments were categorized as excision-only, excision and transposition, excision and cap, excision and repair, or neurolysis and coverage. Data on the proportion of patients with a meaningful reduction in pain were pooled and a random-effects meta-analysis was performed. The effects of confounding, study quality, and publication bias were examined with stratified, meta-regression, and bias analysis. Fifty-four articles met the inclusion criteria, many with multiple treatment groups. Outcomes reporting varied significantly and few studies controlled for confounding. Overall, surgical treatment of neuroma pain was effective in 77% of patients [95% confidence interval: 73-81]. No significant differences were seen between surgical techniques. Among studies with a mean pain duration greater than 24 months, or median number of operations greater than 2 prior to definitive neuroma pain surgery, excision and transposition or neurolysis and coverage were significantly more likely than other operative techniques to result in a meaningful reduction in pain (P < 0.05). Standardization in the reporting of surgical techniques, outcomes, and confounding factors is needed in future studies to enable providers to make comparisons across disparate techniques in the surgical treatment of neuroma pain.

Glial-derived neurotrophic factor (GDNF) promotes both sensory and motor neuron survival. The delivery of GDNF to the peripheral nervous system has been shown to enhance regeneration following injury. In this study we evaluated the effect of affinity-based delivery of GDNF from a fibrin matrix in a nerve guidance conduit on nerve regeneration in a 13 mm rat sciatic nerve defect. Seven experimental groups were evaluated which received GDNF or nerve growth factor (NGF) with the delivery system within the conduit, control groups excluding one or more components of the delivery system, and nerve isografts. Nerves were harvested 6 weeks after treatment for analysis by histomorphometry and electron microscopy. The use of the delivery system (DS) with either GDNF or NGF resulted in a higher frequency of nerve regeneration vs. control groups, as evidenced by a neural structure spanning the 13 mm gap. The GDNF DS and NGF DS groups were also similar to the nerve isograft group in measures of nerve fiber density, percent neural tissue and myelinated area measurements, but not in terms of total fiber counts. In addition, both groups contained a significantly greater percentage of larger diameter fibers, with GDNF DS having the largest in comparison to all groups, suggesting more mature neural content. The delivery of GDNF via the affinity-based delivery system can enhance peripheral nerve regeneration through a silicone conduit across a critical nerve gap and offers insight into potential future alternatives to the treatment of peripheral nerve injuries.