Accuracy of Motor Axon Regeneration across Single Lumen and Multi-Channel Nerve Tubes

Nerve tubes have been developed as experimental tools to investigate peripheral nerve regeneration and for nerve graft repair. The first tubes are now available for clinical repair of nerve gaps up to 3 cm in small nerves (e.g., digital nerves) and are also increasingly used in repair of other nerve lesions. In the repair of mixed nerves or single nerves innervating different muscles, however, conduit repair may lead to inappropriate target reinnervation by dispersion of regenerating axons that occurs inside single lumen tubes. The authors have developed multi-channel conduits that may limit dispersion and lead to better function results by separately guiding groups of regenerating axons. In this study, they investigated the accuracy of motor axon regeneration across single lumen and multi-channel nerve tubes made of poly(lactic co-glycolic acid) in a 1-cm gap in a rat sciatic nerve model.

Axonal dispersion and misrouting were quantified using simultaneous and sequential retrograde tracing techniques. Accuracy of muscle reinnervation was investigated from soleus morphology. Quantitative results of regeneration were evaluated using compound muscle action potential recordings (CMAP), nerve, and muscle morphometry. Results were compared to autograft repair.

After single lumen tube repair, more motoneurons were found to have double projections to the tibial and peroneal nerve (21.4% ± 4.9%) than after autograft repair (5.9% ± 2.9%). Multi-0channel tube repair reduced axonal dispersion (16.9% ± 6.0%), although this difference was not statistically significant (p = 0.24). Percentages of correct routing were similar after single lumen (11.5% ± 3.8%) and multi-channel tube repair (11.6% ± 3.6%)(p = 0.61). The distribution of type I and II fibers in reinnervated soleus muscles, however, suggested more accurate reinnervation after multi-channel tube repair (3:1 compared to the normal distribution of 10:1) than after single lumen (3:2) and autograft repair (3:2). Muscle recovery in total muscle fiber surface area and the mean muscle fiber size was also better after multi-channel tube repair than after single lumen tube repair. The numbers of myelinated fibers were similar after single lumen (3024) and multi-channel tube (2929) repair (p = 0.94) despite a two-time smaller total cross-sectional lumen area. Quantitative results of regeneration in number of myelinated fibers and area of CMAP in this study were still superior after autograft repair.

Dispersion of regenerating axons across single lumen nerve tubes may limit the results for repair of nerves innervating different target muscles. Multi-channel tubes appear to guide regenerating axons better.