Schwann cell delivery via a novel 3D collagen matrix conduit improves outcomes in critical length nerve gap repairs

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  • 1 Department of Neurological Surgery and the Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida; and
  • | 2 Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Alberta, Canada
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OBJECTIVE

The current clinical standard of harvesting a nerve autograft for repair of long-segment peripheral nerve injuries (PNIs) is associated with many potential complications. Guidance channels offer an alternative therapy. The authors investigate whether autologous Schwann cells (SCs) implanted within a novel collagen-glycosaminoglycan conduit will improve axonal regeneration in a long-segment PNI model.

METHODS

Novel NeuraGen 3D collagen matrix conduits were implanted with autologous SCs to investigate axonal regeneration across a critical size defect (13 mm) in male Fischer rat sciatic nerve. Reversed sciatic nerve autografts served as positive controls, and conduits filled with serum only as negative controls. Electrophysiological assessments were made in vivo. Animals were killed at 4 or 16 weeks postinjury, muscle weights were measured, and grafts underwent immunohistochemical and morphometric analysis.

RESULTS

SC survival was confirmed by the presence of green fluorescent protein–labeled SCs within regenerated fibers. Regeneration and elongation of myelinated axons in all segments of the graft were significantly enhanced at 16 weeks in the SC-filled conduits compared to the conduit alone and were statistically similar to those of the autograft. Nerves repaired with SC-filled conduits exhibited onset latencies and nerve conduction amplitudes similar to those of the contralateral controls and autograft (p < 0.05). Adding SCs to the conduit also significantly reduced muscle atrophy compared to conduit alone (p < 0.0001).

CONCLUSIONS

Repair of long-segment PNI of rat sciatic nerve is significantly enhanced by SC-filled NeuraGen 3D conduits. Improvements in the total number of myelinated axons, axon diameter, and myelin thickness throughout SC-filled conduits allow for significant recovery in nerve conduction and a decrease in muscle atrophy.

ABBREVIATIONS

ACG = axon guidance channel; ahSC = autologous human SC; CMAP = compound muscle action potential; GAG = glycosaminoglycan; GFP = green fluorescent protein; GM = gastrocnemius; IHC = immunohistochemical; PBS = phosphate-buffered saline; PI = plantar interossei; PNI = peripheral nerve injury; SC = Schwann cell; TA = tibialis anterior; TB = toluidine blue.

Supplementary Materials

    • Supplemental Figure 1 (PDF 2.62 MB)

Illustration from Kim et al. (pp 1164–1172). Copyright Eui Hyun Kim. Published with permission.

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