Repair of articular cartilage defects one year after treatment with recombinant human bone morphogenetic protein-2 (rhBMP-2)

Background Damaged articular cartilage has a limited ability to repair. Ope rative removal of damaged cartilage and penetration into the subchondral bo ne to allow population of the defect with progenitor cells can result in fi lling of the defect with repair tissue. However, this repair tissue often d egenerates over time because of its inability to withstand the mechanical f orces to which it is subjected, We previously reported that recombinant hum an bone morphogenetic protein-2 (rhBMP-2) improves the repair of full-thick ness defects of cartilage as long as six months postoperatively, We have no w extended that study to examine the qualify of the repair tissue at one ye ar. Methods: Full-thickness defects of cartilage were created in the trochlear groove of twenty-five adult New Zealand White rabbits. Eight defects were l eft empty, eight were filled with a collagen sponge, and nine were filled w ith a collagen sponge impregnated with five micrograms of rhBMP-2, The anim als were killed at fifty-two weeks postoperatively, and the gross appearanc e of the healed defect was assessed. The re-pair tissue was examined histol ogically and was evaluated, according to a grading scale, by four individua ls who were blinded with respect to the treatment, The tissue sections were immunostained,vith antibodies against type-I collagen, type-II collagen, a ggrecan, and link protein. The residence time of the rhBMP-2 in the cartila ge defect was evaluated in vivo with use of scintigraphic, imaging of radio labeled protein. Results: One year after a single implantation of a collagen sponge containi ng five micrograms of rhBMP-2, the defects had a significantly better histo logical appearance than the untreated defects (those left empty or: filled with a collagen sponge). The histological features that showed improvement were integration at the margin,: cellular morphology, architecture,within t he defect,land reformation of the tidemark, The total scores-were also bett er for the defects treated with rhBMP-2 than for the untreated defects, but in no instance was the repair tissue identical to normal articular cartila ge. The thickness of the cartilage in the defects treated with rhBMP-2 was 70 percent that of the normal cartilage, an observation that was identical to that at:twenty-four weeks postoperatively, Immunostaining demonstrated s ignificantly less type-I collagen in the defects treated with rhBMP-2 than in the untreated defects. :Immunostaining for other matrix components shove d-no difference among the treatment groups. The mean residence time of rhBM P-2 in the cartilage defects was eight days with an elimination half-life o f 5.6 days. Detectable amounts of rhBMP-2 were present as long as fourteen days after implantation. Conclusions: The problems associated with operative repair of cartilage inc lude the formation of fibrocartilage rather than normal articular cartilage and the degeneration of that repair tissue over time. Our results demonstr ate that the addition of rhBMP-2 to the operative site after creation of a full-thickness defect results in an improvement in the histological appeara nce and composition of the extracellular matrix at one year postoperatively If these experimental results translate directly to the clinical situation , it is possible that the addition of rhBMP-2 to existing operative treatme nts for the repair of cartilage may improve the repair process and may help to maintain the integrity of the repair tissue.