Karim Sarhane, MD

Purpose:

Substantial advances have been made in enhancing nerve regeneration across gaps through the use of conduits and acellular nerve grafts. However, very few therapeutic approaches have been successfully studied in primary end-to-end repairs. Post-repair histologic studies commonly demonstrate scar tissue between coapted nerve stumps. In this study, we propose a novel semi-permeable nanofiber nerve wrap prepared from FDA approved biocompatible materials (polycaprolactone) to reduce inflammation at nerve coaptation site through inhibition of inflammatory cell infiltration while allowing diffusion of essential nutrients and growth factors.

Methods

Nerve wraps were synthesized by electrospinning of randomly oriented 650-nm nanofibers, and constructs with pores smaller than 10 μm were obtained. Using Thy-1 GFP Sprague-Dawley rats, we performed sciatic nerve transection and epinureal repair (control group) and with wrapping the coaptation site using the neuro-protective nanofiber construct (experimental group). Five weeks later, histologic analysis (Masson’s Trichrome staining, ED1+TUJ1 immunofluorescence co-staining) was performed on nerve sections at the repair site to assess fibrosis (collagen deposition) and
inflammation (macrophage invasion) (n=5/group). Additionally, retrograde labeling was performed, and at the same time, the distal stump was harvested for histo-morphometric evaluation (n=8/group).

Results: Masson’s Trichrome and double immunofluorescence staining (ED1+TUJ1) of nerve longitudinal sections 5 weeks following repair showed a significantly decreased level of intraneural scarring and inflammation in the nanofiber nerve wrap group, as determined by collagen quantification (7.4% ± 1.3 vs. 3.2% ± 1.3, p<0.05) and macrophage counting (32.2 ± 2.4 cells/mm2 vs. 14.6 ± 1.8 cells/mm2, p<0.05) in the repair site. Collagen was trapped outside the nerve wrap in the experimental group. Nerve cross sections taken 5 mm distal to the coaptation site demonstrated a significantly increased number of myelinated axons in the experimental group. Retro- grade labeling showed a trend towards higher number of sensory dorsal root ganglion neurons that regenerated their axons in the nanofiber wrap group when compared to control.

Conclusion

These results provide new insights into a novel targeted anti-inflammatory approach in peripheral nerve repair. Electrospun nanofiber nerve wrap constructs protect the coaptation site from inflammation, promoting scar-free nerve repair, and enhancing axonal regeneration. This new therapeutic strategy utilizing FDA approved products holds great translational potential.