BMP treatment for improving tendon repair. Studies on rat and rabbit Achilles tendons.

Abstract

We wanted to improve tendon healing by adding a growth factor. Bone Morphogenetic Proteins (BMPs) are well known to stimulate bone healing and bone formation. The local environment is of major importance for cell differentiation after a BMP has been added. Cartilage Derived Morphogenetic Proteins (CDMPs) -1, -2 and -3 (BMP 14, 13 and 12 or GDF 5, 6 and 7) form a subgroup in the BMP-family and are closely related to OP-1 (BMP 7). CDMP implants have been shown to induce bone and cartilage as well as tendon and ligament-like tissue. Our hypothesis has therefore been that if a BMP were added in a tendon environment, a tendon-like tissue would be induced. We have developed models in rats and rabbits where the Achilles tendon is transsected. To influence tendon healing, different BMPs (OP-1, CDMP-1. -2 and -3) were added, either on a collagen carrier, or as a local injection into the tendon defect. The tendons were evaluated by histology and mechanical testing at different time-points after transection. The results show that also when the mechanical environment would favour the formation of a tendon-like tissue, OP-1 reduced tendon strength in aid of bone formation. In contrast, CDMP-1, -2 and -3 had a beneficial effect upon tendon healing in rats. More callus tissue was produced than in controls, and strength and stiffness were improved, although minor amounts of bone and cartilage were detected in the tendon callus. Cartilage and bone formation sometimes occur normally during Achilles tendon healing in rats. In the rabbit model, where the healing situation is more similar to the clinical situation, the positive result with CDMP-2 was repeated. Moreover, in rabbits no bone or cartilage was found. The results suggest that conservative treatment of Achilles tendon ruptures with injection of a CDMP in combination with early rehabilitation might afford a good alternative to surgical treatment.