Recombinant Human Bone Morphogenetic Protein-7 Induces Healing in a Canine Long-Bone Segmental Defect Model

Abstract

An ulnar segmental defect model was used in adult male dogs to examine the effect of recombinant human bone morphogenetic protein-7 (recombinant human Osteogenic Protein-1 [rhOP-1]; Creative Biomolecules, Hopkinton, Massachusetts) on new bone induction and healing, and to test the mechanical strength of healed 2.5-cm segmental bone defects. The rhOP-1 composites consisted of a carrier of 500 mg of demineralized, guanidine-extracted, insoluble bovine bone matrix (collagen carrier), reconstituted with rhOP-1. Six animals received 1200 micrograms rhOP-1 unilaterally and were killed at 12 weeks for torsional load-to-failure testing using the contralateral side as a control. Two further animals received varying amounts of rhOP-1 bilaterally and were studied histologically. All defect sites receiving rhOP-1 were completely bridged radiographically by eight weeks. A control composite, containing no rhOP-1, failed to induce new bone formation at any time. Histologically, rhOP-1-treated sites examined at 16 weeks had formation of new cortical and cancellous bone, with normal appearing marrow elements in the reconstituted medullary canal. The torsional strength of the rhOP-1-implanted ulnae averaged 72% of control (range, 30-99%). The angular deformation to failure averaged 92% of control (range, 39-122%). The energy absorption to failure averaged 67% of control (range, 27-111%). This study demonstrates the efficacy of rhOP-1 in healing segmental osteoperiosteal defects in a canine model.