Local sustained delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2).

Local delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2) as a bone graft substitute in spinal fusion was Food and Drug Administration approved on July 2, 2002. Its commercial trade name is INFUSE Bone Graft. It was cleared as a combination biologic device after petitioning the FDA in the early 1990s with the argument that rhBMP-2's effects were only local and not systemic. The protein is applied to a type I collagen sponge at the time of surgery. After a minimum of 15 minutes to allow binding, the collagen sponge is rolled up and placed into a titanium spinal fusion cage. Two of the rhBMP-2 loaded cages are implanted into an intervertebral spinal disc space to promote bone growth across the disc, i.e., spinal fusion. Fusion stops motion at the treated level and ultimately reduces back pain originating from the degenerated disc. This same product was FDA approved for a tibia long bone fresh fracture bone grafting application in August 2004, and for sinus elevation and alveolar defects associated with extraction sockets in March 2007. In addition, a new carrier is under clinical evaluation that will offer longer rhBMP-2 sustained release and compression resistance, further expanding the clinical utility of rhBMP-2.

Effect on bone induction of using contrast media to reconstitute recombinant human bone morphogenetic protein-2 in an ectopic model in rats.

OBJECT: In this study the authors tested the osteoinductive potential of recombinant human bone morphogenetic protein-2 (rhBMP-2) when combined with each of three commercially available contrast media (Conray, Omniscan, and Optiray). METHODS: Initial in vitro and cadaver tests verified the feasibility of using contrast media to visualize absorbable collagen sponge implants containing rhBMP-2 on fluoroscopic radiographic images. For the feasibility studies, lyophilized rhBMP-2 was prepared for injection by reconstitution with contrast media instead of sterile water. For the in vivo study, samples of an rhBMP-2 stock solution were diluted to 0.1 mg/ml by using three contrast media. In each sample, the final solution consisted of 97% contrast medium by volume. Recombinant human bone morphogenetic protein-2 diluted with sterile water for injection was used as a positive control. The rhBMP-2 solutions were applied to 0.5-cm3 collagen sponges and implanted subcutaneously on the thoracic cavity of athymic rats. At 4 weeks, the rats were killed, and the implants were removed. The explants were graded for degree of bone formation by using manual palpation and radiographic and histological assessments. CONCLUSIONS: By all methods of evaluation used, rhBMP-2 diluted with Omniscan was equivalent to rhBMP-2 diluted with sterile water in inducing bone formation. Both Conray and Optiray were shown to inhibit the osteoinductive potential of rhBMP-2.