Development of heparin-conjugated nanofibers and a novel biological signal by immobilized growth factors for peripheral nerve regeneration.
Aligned fibers have been used as a scaffold of nerve guidance conduit owing to their guiding function of neural cells for peripheral nerve regeneration. However, the recovery performance of nerve guidance conduits using aligned fibrous scaffold is insufficient, and further improvements in scaffold function is required for promoting regeneration. In this study, we developed aligned heparin-conjugated fibers and supplied a biological signal to neural cells by the growth factors immobilized through heparin. Results indicated that neural model cells (PC12 cells) were cultured well on the scaffold without inhibiting cell adhesion by heparin conjugation and exhibited more vigorous cell proliferation than in a heparin-free condition. The cells extended their neurites along the fiber direction. Furthermore, PC12 cells on the heparin-conjugated fibrous scaffold pre-exposed to a nerve growth factor solution sprouted more neurites compared to those of heparin-free condition. These results verified that our scaffold exhibited high biocompatibility to neural cells and could maintain an effective local concentration of growth factors on the scaffold surface. Therefore, aligned heparin-conjugated fibers are promising scaffolds of nerve guidance conduits for promoting peripheral nerve regeneration by the combinatorial effect of topological and biological signals.