Immunohistochemical demonstration of growth factors at the tendon-bone interface in anterior cruciate ligament reconstruction using a rabbit model

Background. The success of anterior cruciate ligament (ACL) reconstruction using tendon grafts depends on biological integration between the tendon and bone. Growth factors play a significant role in this integration process, but few studies have defined the regulating mechanisms of these growth factors during tendon-bone healing. The aim of the present study was to clarify the relationship between the histological changes and the expression of endogenous growth factors at the tendon-bone interface. Methods. Using intra-articular tendon transfer in rabbits to stimulate ACL reconstruction, the presence of fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF), bone morphogenetic protein-2 (BMP-2), and BMP-7 at the interface between the tendon and bone was evaluated immunohistochemically. Histological and immunohistochemical investigations were performed at 1, 3, 6, and 12 weeks after surgery. Results. Fibrous integration of the tendon graft to the bone was observed immediately after tendon transfer and followed remodeling of the bone tunnel. Fibroblast and vascular growth factors were found in abundance at the tendon-bone interface in the first 3 weeks of graft incorporation, but were absent in the 12-week specimens. BMPs were found throughout the 12-week study period and were observed at high concentrations near the bone. Conclusions. These results indicate that FGF-2 and VEGF contribute to fibrous integration between the tendon and bone during the early postoperative stage, and that BMP-2 and BMP-7 are specifically involved in bone remodeling leading to osseous integration. The early stages of tendon-bone healing might be important in controlling the integration process of the interface in ACL reconstruction surgery as seen in this rabbit model.