Effect on bone induction of using contrast media to reconstitute recombinant human bone morphogenetic protein-2 in an ectopic model in rats.
OBJECTIVE
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.
Zanella
John M
JM
Medtronic Spinal and Biologics Division, Memphis, Tennessee, USA.
Oliver
Colleen
C
Peckham
Steve M
SM
McKay
Bill
B
Toth
Jeffrey M
JM
Boden
Scott D
SD
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D018786:Bone Substitutes; D003287:Contrast Media / Q000494:pharmacology*; D005240:Feasibility Studies; D019786:Gadolinium DTPA / Q000494:pharmacology*; D007482:Iothalamate Meglumine / Q000494:pharmacology*; D010012:Osteogenesis / Q000187:drug effects*; D019736:Prostheses and Implants; D051381:Rats; D011923:Rats, Nude; D011994:Recombinant Proteins / Q000494:pharmacology*; D015503:Surgical Sponges; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014283:Triiodobenzoic Acids / Q000494:pharmacology*
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D018786:Bone Substitutes; D003287:Contrast Media; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D014283:Triiodobenzoic Acids; C499469:recombinant human bone morphogenetic protein-2; C064925:gadodiamide; D019786:Gadolinium DTPA; C054871:ioversol; D007482:Iothalamate Meglumine