Polyethylene glycol fusion repair prevents reinnervation accuracy in rat peripheral nerve

Functional recovery following a peripheral nerve injury is made easier when regenerating axons correctly reinnervate their original targets. Polyethylene glycol (PEG) has recently been used in attempts to fuse severed peripheral axons during suture‐based repair, but an analysis of target selectivity following such repair has not been undertaken. The rat femoral nerve (in which muscle and cutaneous pathways comingle proximally but segregate distally into separate terminal nerve branches) is a convenient in vivo model for assessing motor neuron regeneration accuracy. The present study uses retrograde labeling of motor neurons to compare reinnervation accuracy after suture‐based nerve repair with and without PEG fusion. The results show that adding PEG to the suture repair site blocked the preference of motor neurons to reinnervate correctly the distal terminal nerve branch to muscle that was seen with suture repair. Retrograde transport and diffusion studies also determined that PEG fusion allowed passage of probes across the repair site, as has previously been seen, but did not result in motor neuron labeling in the spinal cord. The results suggest that PEG fusion disrupts the beneficial trophic influence of muscle on motor neuron reinnervation accuracy normally seen after suture repair and that such fusion‐based approaches may be best suited to nerve injuries in which accurate target reinnervation at the terminal nerve branch level is not a priority. © 2016 Wiley Periodicals, Inc. When a cut peripheral nerve is repaired with suture, regenerating motor neuron axons have access to trophic signals from the muscle through the nerve. When polyethylene glycol is added to the suture repair to promote axonal fusion, access is blocked to the muscle's trophic signals.