Heparin-Binding-Affinity-Based Delivery Systems Releasing Nerve Growth Factor Enhance Sciatic Nerve Regeneration

Abstract

The controlled delivery of nerve growth factor (NGF) to the peripheral nervous system has been shown to enhance nerve regeneration following injury, although the effect of release rate has not been previously studied with an affinity-based delivery system (DS). The goal of this research was to determine if the binding site affinity of the DS affected nerve regeneration in vivo using nerve guidance conduits (NGCs) in a 13-mm rat sciatic nerve defect. These DSs consisted of bi-domain peptides that varied in heparin-binding affinity, heparin and NGF, which binds to heparin with moderate affinity. Eight experimental groups were evaluated consisting of NGF with DS, control groups excluding one or more components of the DS within silicone conduits and nerve isografts. Nerves were harvested 6 weeks after treatment for analysis by histomorphometry. These DSs with NGF resulted in a higher frequency of nerve regeneration compared to control groups and were similar to the nerve isograft group in measures of nerve fiber density and percent neural tissue, but not in total nerve fiber count. In addition, these DSs with NGF contained a significantly greater percentage of larger diameter nerve fibers, suggesting more mature regenerating nerve content. While there were no differences in nerve regeneration due to varying peptide affinity with these DSs, their use with NGF enhanced peripheral nerve regeneration through a NGC across a critical nerve gap.