"Peripheral Nerve Matrix hydrogel promotes recovery after nerve transection and repair."

Abstract

Nerve transection is the most common form of peripheral nerve injury. Treatment of peripheral nerve injury has primarily focused on stabilization and mechanical cues to guide extension of the regenerating growth cone across the site of transection. Here we investigate the effects of a peripheral nerve matrix (PNM) hydrogel on recovery following nerve transection. We use rodent models to determine the effect of PNM on axon extension, electrophysiological nerve conduction, force generation and neuromuscular junction formation after nerve transection and repair. We complemented this work with in vivo and in vitro FACS and immunohistochemistry approaches to determine the effects of PN on critical cell populations early after repair. Extension of axons from the proximal stump and overall GFP+ axon volume within the regenerative bridge were increased in the presence of PNM compared with an empty conduit (p< 0.005) 21 days after repair. PNM increased electrophysiological conduction (CMAP amplitude) across the repair site (p<0.05) and neuromuscular junction formation (p=0.04) 56 days after repair. PNM produced a shift in macrophage phenotype in vitro and in vitro (p<0.05) and also promoted regeneration in a murine model used to characterize the early immune response to PNM (p<0.05). PNM, delivered by subepineural injection, promoted recovery following nerve transection with immediate repair, supporting a beneficial macrophage response, axon extension and downstream remodeling using a range of clinically relevant outcome measures.