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.