Improvement of peripheral nerve regeneration in acellular nerve grafts with local release of nerve growth factor

Abstract

Previous studies have demonstrated the potential of growth factors in peripheral nerve regeneration. A method was developed for sustained delivery of nerve growth factor (NGF) for nerve repair with acellular nerve grafts to augment peripheral nerve regeneration. NGF-containing polymeric microspheres were fixed with fibrin glue around chemically extracted acellular nerve grafts for prolonged, site-specific delivery of NGF. A total of 52 Wistar rats were randomly divided into four groups for treatment: autografting, NGF-treated acellular grafting, acellular grafting alone, and acellular grafting with fibrin glue. The model of a 10-mm sciatic nerve with a 10-mm gap was used to assess nerve regeneration. At the 2nd week after nerve repair, the length of axonal regeneration was longer with NGF-treated acellular grafting than acellular grafting alone and acellular grafting with fibrin glue, but shorter than autografting (P < 0.05). Sixteen weeks after nerve repair, nerve regeneration was assessed functionally and histomorphometrically. The percentage tension of the triceps surae muscles in the autograft group was 85.33 +/- 5.59%, significantly higher than that of NGF-treated group, acellular graft group and fibrin-glue group, at 69.79 +/- 5.31%, 64.46 +/- 8.48%, and 63.35 +/- 6.40%, respectively (P < 0.05). The ratio of conserved muscle-mass was greater in the NGF-treated group (53.73 +/- 4.56%) than in the acellular graft (46.37 +/- 5.68%) and fibrin glue groups (45.78 +/- 7.14%) but lower than in the autograft group (62.54 +/- 8.25%) (P < 0.05). Image analysis on histological observation revealed axonal diameter, axon number, and myelin thickness better with NGF-treated acellular grafting than with acellular grafting alone and acellular grafting with fibrin glue (P < 0.05). There were no significant differences between NGF-treated acellular grafting and autografting. This method of sustained site-specific delivery of NGF can enhance peripheral nerve regeneration across short nerve gaps repaired with acellular nerve grafts.