The Different Effects of TGF-β1, VEGF and PDGF on the Remodeling of Anterior Cruciate Ligament Graft

Abstract

Rupture of anterior cruciate ligament (ACL) is a common knee trauma which leads to anterior knee instability. The ACL has long been thought to have poor capacity for healing with suture repair. ACL reconstruction is the standard of care which can restore the knee stability of ACL deficit knee. Although ACL reconstruction is an excellent operation for restoring the sagittal plane stability of the knee, significant problems remain. Studies have demonstrated that remodeling of the graft usually takes longer than expected, and many patients develop arthritis after an ACL tear, even if they have a reconstruction, with rates as high as 78% reported at 14 years post-operatively (1). In ACL reconstruction, inflammation and necrosis of the graft can occur immediately after transplantation. The graft then undergoes revascularization and cellular repopulation from an extrinsic origin, followed by a remodeling period. In the early phase, the properties of the grafted tendon are deteriorated and do not recover to physiological levels even at 18 months after surgery (2). Therefore, the main goals of ACL reconstruction are to prevent the deterioration of grafted tendon and accelerate mechanical restoration of the deteriorated graft. New solutions are needed to accelerate and improve remodeling of tendon grafts. The ACL graft remodeling process is regulated by a complex growth factor network. Many growth factors have been evaluated for their ability to stimulate tendon and ligament healing in vitro and in vivo. In enhancing ligament repair, the most interesting candidates are insulin-like growth factor-I (IGF-I), transforming growth factor ┚1 (TGF┚1), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), platelet derived growth factor (PDGF), and basic fibroblast growth factor (bFGF). PDGF and VEGF appear in the early stage of reconstruction, during the stage of graft maturing, the granular tissue becomes ligament-like tissue and both PDGF and VEGF are not able to be detected gradually, as the replacement, TGF┚1and other cytokines are involving in the reconstruction process to mature the ligament. TGF┚1 is the main cytokine for the maturing of ligament. Studies have