Controlling the Release of Neurotrophin-3 and Chondroitinase ABC Enhances the Efficacy of Nerve Guidance Conduits

Abstract

Nerve guidance conduits (NGCs) have the potential to replace autografts in repairing peripheral nerve injuries, but their efficacy still needs to be improved. The efficacy of NGCs is augmented by neurotrophic factors that promote axon growth and by enzymes capable of degrading molecules that inhibit axon growth. In the current study, two types of NGCs loaded with factors (both neurotrophin-3 and chondroitinase ABC) are constructed and their abilities to repair an 8 mm gap in the rat sciatic nerve are examined. The factors are encapsulated in microparticles made of a phase-change material (PCM) or collagen and then sandwiched between two layers of electrospun fibers. The use of PCM allows to achieve pulsed release of the factors upon irradiation with a near-infrared laser. The use of collagen enables slow, continuous release via diffusion. The efficacy is evaluated by measuring compound muscle action potentials (CMAP) in the gastrocnemius muscle and analyzing the nerve histology. Continuous release of the factors from collagen results in enhanced CMAP amplitude and increased axon counts in the distal nerve relative to the plain conduit. In contrast, pulsed release of the same factors from PCM shows a markedly adverse impact on the efficacy, possibly by inhibiting axon growth.

Keywords: chondroitinase ABC; controlled drug release; nerve guidance conduits; neurotrophin-3; peripheral nerve repair.