Improved peripheral nerve regeneration with sustained release nerve growth factor microspheres in small gap tubulization.

Abstract

OBJECTIVE: To evaluate the long-term results of the use of nerve growth factor (NGF)-loaded poly-D, L-lactide-co-glycolide (PLGA) microspheres for improve nerve regeneration with small gap tubulization. METHODS: NGF microspheres were prepared by a modified W/O/W emulsion solvent evaporation method. Forty-eight male SD rats were separated into 4 groups and received a chitin conduit to bridge a sciatic nerve injury left a 2 mm gap. Saline (Group A), 20 ng/ml NGF solution (Group B), blank PLGA microspheres (Group C), or 40 ng/ml NGF-loaded microspheres (Group D) was injected in the gap. Each group had two study endpoints, 3 months subgroup and 1 year subgroup. RESULTS: The myelinated fiber count at 2 mm distal to the conduit at 1 year was slightly less than at 3 months in all groups (P>0.05). However, the maturity of the myelinated nerves at 1 year was obviously improved. The fiber count, myelin sheath thickness, axon area of NGF microsphere group were significantly higher than the saline groups at 3 months (P=0.05, P<0.05, and P<0.05, respectively). The SFI was significantly improved in NGF microspheres group compared to the saline group and NGF solution group at 1 year (P<0.05, and P<0.05, respectively). CONCLUSIONS: The results demonstrated that the release of NGF microspheres in small gap tubulization benefit on peripheral nerve injury facilitated nerve regeneration histologically, especially for the maturity of early regenerative nerve fibers and also had an effect on functional recovery in the long term.