Collagen Nerve Conduits and Stem Cells for Peripheral Nerve Gap Repair

Introduction: Traumatic nerve injuries often require a graft to bridge the gap. Collagen nerve guides can be used in clinical practice, but their use is generally limited to lesions up to 3 cm. Autologous cell transplantation may be an alternative strategy to support regeneration over longer gaps. We coupled FDA-approved collagen conduits to regenerative cells and investigated initial effects on nerve regeneration.

Methodology and Material: In vitro tests showing satisfactory cell retaining into collagen conduits (NeuraGen nerve guides) and electronic microscopy analysis of cell adherence were performed. In the in vivo experiment, three groups (n = 5 each) of NeuraGen nerve guides were seeded with various cell types: primary Schwann cells (SC), SC-like differentiated mesenchymal and adipose-derived stem cells (dMSC, dASC). A control group was formed respectively by empty NeuraGen nerve guides. Conduits were used to cross a 1-cm rat sciatic nerve gap in a 2-weeks experiment. Immunohistochemical analysis on frozen longitudinal sections was performed to assess axonal regeneration and Schwann cell infiltration.

Results: Primary Schwann cells showed significant improvement in distal stump sprouting, without significant differences in proximal regeneration distances among experimental groups. dMSC and dASC-loaded conduits showed a diffuse sprouting pattern, while primary Schwann cells showed an enhanced cone pattern and a typical sprouting along the conduits walls, suggesting an increased affinity for the collagen type I fibrillar structure.

Conclusions: This work shows the high affinity of regenerative cells for collagen nerve guides, which can be used as efficient vehicle for cell delivery in tissue engineering applications. However, data suggest that a good cell retaining is not always associated with effective cell function, as the different types of cells did not have a significant effect on proximal nerve regeneration. The commercially available nerve guide could be modified in future tissue-engineering applications (e.g., extracellular matrix peptides) to better exploit cell potential.