Enhanced tendon healing with GDF 5 and 6

Between ruptured tendon ends, undifferentiated mesenchymal cells invade the hematoma and differentiate to form a tendon regenerate. This differentiati on is partly directed by mechanical stimuli, which are difficult to apply a nd control clinically. For example, closed treatment of Achilles tendon rup tures is associated with a risk of rerupture of the regenerate. Improved te ndon 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 i n rats, indicating a new way to improve tendon heating. We transected the A chilles tendon in 66 rats and denervated the calf muscle. Denervation serve d to reduce the mechanical stimulation to the tendon callus by eliminating muscle contractions. GDF 5 or 6 were implanted on collagen sponges in the t endon defects in two doses and compared to collagen sponges alone. The rats were killed after 2 weeks and the tensile strength of the tendon regenerat e was found to be increased by both proteins in a seemingly dose-dependent manner.