Evaluation of a GDNF-eluting nanofibrous PCL conduit in a mouse model of peripheral nerve injury

Abstract

Severe, gap-type peripheral nerve injuries often require surgical intervention in the form of a nerve autograft or synthetic nerve guidance scaffold to promote axonal regeneration and functional recovery. In this study, nerve guidance conduits (NGCs) were fabricated from aligned polycaprolactone (PCL) nanofibres with or without encapsulated glial cell line-derived neurotrophic factor (GDNF), and a fibrin sealant-based hydrogel. These constructs were evaluated in a murine sciatic nerve transection model using Thy1-YFP-H mice, allowing regenerating axons to be visualised in transverse sections throughout the constructs. Both PCL + GDNF and PCL-only conduits facilitated Schwann cell migration and successful axonal regeneration across the site of injury. Nerve autografts, the positive control, demonstrated the highest regenerating axon count in the distal stump, although statistical significance was not observed between groups. These results demonstrate that NGCs fabricated using aligned PCL nanofibres reliably facilitate nerve regeneration across nerve gaps to a degree, but require further investigation for application in peripheral nerve repair. Future studies that optimise growth factor delivery and conduit design would be beneficial to improve regenerative outcomes.