The Journal of Bone and Joint Surgery 79:1452-63 (1997)
© 1997 The Journal of Bone and Joint Surgery, Inc.
The Effect of Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2) on the Healing of Full-Thickness Defects of Articular Cartilage*
RANI S. SELLERS, D.V.M. ,
DIANE PELUSO, H.T.L. and
ELISABETH A. MORRIS, D.V.M., CAMBRIDGE, MASSACHUSETTS
Investigation performed at Genetics Institute, Cambridge
Articular cartilage has a limited capacity for repair. We investigated the effect of rhBMP-2 (recombinant human bone morphogenetic protein-2) on the healing of full-thickness osteochondral defects in adult New Zealand White rabbits. A single defect, three millimeters wide by three millimeters deep, was created in the trochlear groove of the right femur in eighty-nine rabbits. The defect was either left empty, filled with a plain collagen sponge, or filled with a collagen sponge impregnated with five micrograms of rhBMP-2. The animals were killed at four, eight, or twenty-four weeks, and the repair tissue was examined histologically and evaluated with use of a grading scale. The defects also were examined immunohistochemically for the presence of type-II collagen at four and eight weeks. The rate of bone repair was evaluated with fluorescent labeling of bone at two and four weeks and with use of fluorescence microscopy at eight weeks.
Treatment with rhBMP-2 greatly accelerated the formation of new subchondral bone and improved the histological appearance of the overlying articular surface. At twenty-four weeks, the thickness of the repair cartilage was 70 per cent that of the normal adjacent cartilage and a new tidemark usually had formed between the repair cartilage and the underlying subchondral bone. The average total scores on the histological grading scale were significantly better (p < 0.01) for the defects treated with rhBMP-2 than for the untreated defects (those left empty or filled with a plain collagen sponge) at all time-points. Immunostaining with an antibody against type-II collagen showed the diffuse presence of this cartilage-specific collagen throughout the repair cartilage in the treated defects. The untreated defects demonstrated minimum staining with this antibody.
CLINICAL RELEVANCE: The operative removal of cartilage damaged as a result of trauma or focal osteoarthrosis is of little value because of the limited capability of articular cartilage to repair. If the damaged cartilage were to be removed and the tissue were induced to heal, the self-perpetuating process of osteoarthrosis might be prevented. We describe the capacity of rhBMP-2 to accelerate the healing of full-thickness defects of articular cartilage and to improve the histological appearance and biochemical characteristics of the repair cartilage. These improvements were evident as long as twenty-four weeks postoperatively in adult rabbits. Because of the technical simplicity of delivering a recombinant protein growth factor compared with transplanting cells, and because of the improvement in healing afforded by rhBMP-2, the use of this growth factor and related proteins to influence the healing of defects of articular cartilage should be investigated further.
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