Surgical repair of injured peripheral nerve often fails to restore adequate function after nerve injury. Misdirection
of regenerative axons is a primary cause of this failure. Motor axons reaching skin provide no function and block
pathways which they occupy; cutaneous axons reaching muscle may function, but will provide incorrect
information from the wrong location. Recent experiments suggest a solution to this problem. Motor axons
regenerating in the rat femoral nerve produce multiple collateral sprouts; motor/sensory specificity is improved by
pruning collaterals from the cutaneous nerve while keeping those in motor Schwann cell tubes. Specificity may be
enhanced by crushing the nerve before repair. This mechanical manipulation increases the collateral sprout
formation, allowing each motor neuron to sample more pathways, and thus improve its chances of reinnervating
muscle instead of skin. However biologically significant, this observation does not lend itself to clinical application
because of the requirement of pre-injury treatment. If a similar effect could be produced at the time of nerve
suture, the outcome of clinical nerve repair could be substantially improved. In the proposed research, we will
apply a combination of trophic factors, such as IGF I, PDGF, CNTF and NT 3 using a miniosmotic pump for
delivery, to enhance regenerative sprouting of motor axons at the site of nerve repair. Regenerative sprouting and
specificity will be assessed using a double labeling technique, functional outcome by gait analysis and direct
muscle stimulation.