Bone morphogenetic protein binding peptide mechanism and enhancement of osteogenic protein-1 induced bone healing

Study Design: In vitro and in vivo evaluation of BBP interactions with BMP. Objective: To explore bone morphogenetic protein-binding peptide (BBP)'s mechanism of action, investigate an extended repertoire for BBP applications, and evaluate the usefulness of BBP as a surgical adjuvant when used with recombinant human osteogenic protein-1 (rhOP-1). Summary Of Background Data: Bone morphogenetic proteins (BMPs) are osteoinductive proteins that provide a potential alternative to autograft. Their utility is limited by cost, and potential dose-dependent risks, such as local inflammatory reactions and ectopic bone formation. BBP, a cyclized synthetic peptide, avidly binds recombinant human BMP-2(rhBMP-2) and has been shown to accelerate and enhance its osteogenic qualities. Methods: BBP binding with 4 growth factors from the transforming growth factor-beta family were assessed using surface plasmon resonance. The in vivo retention of rhBMP-2 was quantified by comparing the percentage of retained [I]-labeled rhBMP-2 in absorbable collagen sponge implants with or without BBP at 1, 3, and 7 days postimplantation. The adjunctive effect of BBP with rhOP-1-induced bone growth was evaluated by comparing time to fusion and fusion rates in a rodent posterolateral fusion model with 2 different doses of rhOP-1 with or without BBP. Results: BBP bound all 4 growth factors with an intermediate affinity. The in vivo retention of rhBMP-2 alone ranged from about 40% on day 1 to about 30% on day 7, whereas, the retention of rhBMP-2 in the presence of BBP was about 85% on day 1 and about 55% on day 7. The addition of BBP to rhOP-1 resulted in significantly earlier and greater fusion rates than achieved with rhOP-1 alone. Conclusion: The mechanism of the BBP enhanced osteoinductive properties of BMPs involves the binding and retention of the growth factor, resulting in a prolonged exposure of BMP to the desired fusion site. The use of BBP in conjunction with BMPs may prove to provide satisfactory fusion outcomes, while reducing the costs and side effects associated with BMP use.