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.

Nerve growth factor with fibrin glue in end-to-side nerve repair in rats

“…The mass of the left CTM of group B was inferior to the other groups indicating expected nerve post-lesion muscle atrophy 14 . The animals in groups C to F had similar muscle mass values among them, superior to group B, showing that the performed repair -independent from the used techniquedetermined favorable repercussion in the muscle.…”

“…According to Santos et al 13 systemic administration was not a good option because of the large amounts of substance needed and the impossibility of knowing the concentration of the agent at the nerve lesion site. In the same way implantable infusion pumps, among other options, despite presenting excellent results, were difficult to be applied at the day There was no difference among the mass of the animals, in all groups, in the first or in the last measurements, what presented the homogeneity of the sample and indicated that the surgery did not interfere in the animals eating habits 14 . In addition to that, such results allowed us to make comparisons among others varieties studied such as for example, the CTM mass, that is proportional to the animal mass 4 .…”

Regeneración de las lesiones críticas del nervio periférico con factores de crecimiento. Estudio experimental

“…Yu et al, 2009, examinaron el efecto histológico de NGF, revelando un diámetro axonal, número total y grosor de la mielina mejor con NGF que en los nervios reparados con injerto acelular solo y con sellador de fibrina.…”

“…Con este proyecto de investigación, hemos intentado avanzar en la línea ya iniciada en investigaciones previas de nuestro grupo de trabajo, en búsqueda de diferentes formas de presentar el injerto muscular como puente en las lesiones críticas nerviosas, y las opciones de las que disponemos para enriquecerlo biológicamente, apoyando nuestro proyecto en las actuales experimentaciones con factores de crecimiento (Gordon T, 2009;Yu et al, 2009;Moimas et al, 2013).…”

“…Yu et al, 2009, looked at the histological effect of NGF trated acellular grafts, revealing an axonal diameter, total number and thickness of myelin better after NGF treatment than in nerves repaired with acellular grafts alone and acellular grafts with fibrin sealant.…”