Enhanced tendon healing with GDF 5 and 6

Abstract

Between ruptured tendon ends, undifferentiated mesenchymal cells invade the hematoma and differentiate to form a tendon regenerate. This differentiation is partly directed by mechanical stimuli, which are difficult to apply and control clinically. For example, closed treatment of Achilles tendon ruptures is associated with a risk of rerupture of the regenerate. Improved tendon healing by exogenous growth factors has not previously been reported. Three proteins in the Bone Morphogenetic Protein (BMP) family--namely Growth and Differentiation Factors (GDFs) 5, 6 and 7--have recently been shown to induce a tendon- or ligament-like tissue after intramuscular implantation in rats, indicating a new way to improve tendon healing. We transected the Achilles tendon in 66 rats and denervated the calf muscle. Denervation served to reduce the mechanical stimulation to the tendon callus by eliminating muscle contractions. GDF 5 or 6 were implanted on collagen sponges in the tendon defects in two doses and compared to collagen sponges alone. The rats were killed after 2 weeks and the tensile strength of the tendon regenerate was found to be increased by both proteins in a seemingly dose-dependent manner.