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The Journal of Bone and Joint Surgery (American) 85:116-123 (2003)
© 2003 The Journal of Bone and Joint Surgery, Inc.

Orthopaedic Applications

Repair of Articular Cartilage Defects with Osteogenic Protein-1 (BMP-7) in Dogs

Stephen D. Cook, PhD, Laura P. Patron, BSE, Samantha L. Salkeld, MSE and David C. Rueger, PhD

Abstract

Background: Articular cartilage injury has a poor prognosis for repair. Mesenchymal cells, when exposed to osteogenic proteins and other cytokines, can differentiate into cells that behave phenotypically as chondrocytes. In this study, we examined the ability of recombinant human osteogenic protein-1 (rhOP-1 or rhBMP-7) to elicit the repair of osteochondral defects in dogs.

Methods: Bilateral osteochondral defects that were 5 mm in diameter by 6 mm deep were surgically created in the medial femoral condyles of sixty-five adult dogs. rhOP-1-treated (100 mg of a 3.5-mg rhOP-1/g bovine bone-derived Type-I collagen device) and control defects (untreated or treated with 100 mg bovine bone-derived collagen implants) were evaluated grossly and histologically at six, twelve, sixteen, twenty-six, and fifty-two weeks postoperatively. The influence of protected initial weight-bearing and surgical placement of periosteal flaps was also evaluated.

Results: Gross and histologic grading of the defect repair indicated improvement in the rhOP-1-treated defects compared with that in the controls. Grossly, the repair tissue in the rhOP-1-treated defects was continuous with the adjacent intact cartilage and appeared translucent. By comparison, the repair tissue in the control defects was discontinuous and opaque or inhomogeneous in nature. Histologically, maturing cartilage similar in appearance to the intact articular cartilage was present in the rhOP-1-treated defects. Cartilage at the defect interface was minimally degraded. The control defects were filled primarily with fibrous tissue and fibrocartilage. Significant differences based upon treatment type were observed at twelve weeks, sixteen weeks, and for all time-periods combined (p = 0.0385, p = 0.0070, and p = 0.0026, respectively).

Conclusion: rhOP-1 (rhBMP-7) induced hyaline cartilage-like repair of full-thickness osteochondral defects in a dog model. Differences in cartilage repair were maintained at fifty-two weeks postoperatively with no significant degradation of the rhOP-1-induced repair tissue.

Clinical Relevance: The dog osteochondral defect model is a challenging one that reflects the difficulties of eliciting articular cartilage repair that are seen in the clinical setting. The results of this study indicate that rhOP-1 may improve the repair of articular cartilage, and they demonstrate the importance of further investigation to characterize the effects of growth factors on the cartilage repair process.


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M. A. Mont, P. S. Ragland, B. Biggins, G. Friedlaender, T. Patel, S. Cook, G. Etienne, A. Shimmin, R. Kildey, D. C. Rueger, et al.
Use of Bone Morphogenetic Proteins for Musculoskeletal Applications: An Overview
J. Bone Joint Surg. Am., December 1, 2004; 86(suppl_2): 41 - 55.
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