Sustainable release of nerve growth factor for peripheral nerve regeneration using nerve conduits laden with Bioconjugated hyaluronic acid-chitosan hydrogel

Abstract

Peripheral nerve regeneration following injury is often incomplete, resulting in significant personal and socioeconomic costs. Nerve conduits have been developed to complement or replace autologous nerve grafts. In this study, repairing injured peripheral nerves in rats is investigated by fabricating poly(D, l-lactic acid) (PDLLA)/β-tricalcium phosphate (β-TCP) nerve conduits filled by injectable chitosan (CS)-hyaluronic acid (HA) hydrogels featuring sustained release of nerve growth factor (NGF). All CS-HA hydrogels have porosities higher than 80%. The mass loss of the CS-HA hydrogels reaches 70% in 8 weeks. In vitro experiments suggest that the CS-HA/NGF hydrogels are suitable for the adhesion, spreading, and differentiation of neuronal cells, which also allow for sustained release of NGF. In vivo studies on the repair of 10-mm sciatic nerve defects in rats are used to assess nerve repair rate through walking track analysis, gastrocnemius weight analysis, and histological analysis. It is shown that the PDLLA/β-TCP nerve conduits laden with CS-HA/NGF hydrogels have a significant positive effect on the axon regeneration and myelination, compared to the PDLLA/β-TCP hollow nerve conduits and the autograft group. These results show that the CS-HA/NGF injectable hydrogel can effectively promote nerve regeneration making it a good candidate in the field of neural tissue engineering.