Dose-effect relationship of vascular endothelial growth factor with intrinsic healing of rabbit's achilles tendon

Aiyong HE; Tingting MO

ABSTRACT

BACKGROUND:

A variety of growth factors are involved in regulating cell proliferation and matrix synthesis at the tendon healing process. Vascular endothelial growth factor (VEGF) plays a powerful role on the tissue healing and regeneration. At present, few studies report the VEGF at the process of endogenous tendon healing.

OBJECTIVE:

To investigate the dose-effect relationship of intrinsic healing of rabbit's achilles tendon, which was topically separated by silicone tube, with the VEGF application. DESIGN, TIM E AND

SETTING:

Randomized control animal experiments were performed in the Central Animal Laboratory in the Second Xiangya Hospital of Central South University from November 2007 to April 2008. MATERIALS Forty-eight healthy rabbits, weighing 2.5-3.0 kg, were used to establish the tendon rabbit injury models and were divided into 4 groups randomly, termed blank group and VEGF 100 ng, 50 ng, 10 ng groups, with 12 animals for each group.

METHODS:

The gastrocnemius bundle branch and soleus muscle bundle branch of the right achilles tendon were sutured after surface skin and subcutaneous tissue discission. The gastrocnemius bundle branch was transected at 2 cm above calcaneal bone insertion and a 2-cm silicone tube was applied to separate the site of suture using 5-0 modified Kessler method. The site of suture was treated with nothing in silicone tube as the blank control group. In other three groups, the site of suture was treated with 100, 50, 10 ng VEGF in silicone tube at the operation day and 7, 14, 21 days post-operation. MAIN OUTCOME

MEASURES:

At 2, 4, 6 weeks post-operation, the achilles tendon of 4 rabbits in each group were harvested for gross observation and histological evaluation.

RESULTS:

Compared with 2 and 4 weeks post-operation, the peripheral tissue's adhesion out of the silicon tube at 6 weeks was relieved and required to be separated using passive or operating knife. There were no significant differences in the grading of tendon adhesion between groups at 6 weeks post-operation (P > 0.05). The broken end of the achilles tendon in the silicon tube was connected with new-bom achilles tendon fibre tissues. The healing was well in each group, and the VEGF groups were superior to blank control group (P < 0.05). At 2, 4, 6 weeks post-operation, the fibroblast counting in the 100 ng and 50 ng VEGF groups was greater than that in the 10 ng VEGF group (P < 0.05), but no significant differences were found in the fibroblast counting between 100 ng and 50 ng VEGF groups (P > 0.05). The content of collagen fibres had no significant difference among three VEGF groups. The fibroblast counting and the content of collagen fibres in the VEGF groups were higher than that in the blank control group (P < 0.05).

CONCLUSION:

The exogenous application of different doses of VEGF at achilles tendon repair site can facilitate the proliferation and maturation of the fibroblasts, increase the secretion of collagen and promote the maturation of collagen fibres, thus facilitating intrinsic healing of the achilles tendon. The 100 ng and 50 ng VEGF is better than 10 ng VEGF with regard to the promotion of achilles tendon healing, and no difference is observed between 100 ng and 50 ng.