Improved Healing Efficacy in Canine Ulnar Segmental Defects With Increasing Recombinant Human Bone Morphogenetic Protein-2/Allograft Ratios

Abstract

A validated canine critical-sized segmental defect model was used to compare efficacy of volumetric ratios of recombinant human bone morphogenetic protein-2 (rhBMP-2)/absorbable collagen sponge (ACS) with cancellous allograft bone or biphasic calcium phosphate ceramic granules using radiographic, biomechanical, and histologic analyses. Eighteen mixed-breed hounds received bilateral critical-sized ulnar segmental defects. The six treatment groups included 1:5, 1:2, and 1:1 volumetric ratios of rhBMP-2/ACS to cancellous allograft chips; a 1:1 volumetric ratio of rhBMP-2/ACS to biphasic calcium phosphate ceramic granules; iliac crest autograft alone; and cancellous allograft chips alone (n = 6 ulna per group). Animals were euthanized at 12 weeks and analyzed by radiography, torsion testing, and histology. rhBMP-2/ACS groups demonstrated higher radiographic union than autograft or allograft at 12 weeks. Both treatment groups receiving a 1:1 ratio demonstrated union rates of 100% (12/12 ulna) compared with 17% (1/6) and 0% (0/6) for autograft and allograft, respectively. Torsion testing to failure demonstrated significant increases in maximum torque for all rhBMP-2 groups compared with autograft, but no differences between the rhBMP-2 groups. Ulnae treated with the 1:1 volume ratio of rhBMP-2/ACS to ceramic had the highest histologic union grades followed by 1:1 and 1:2 volume ratios of rhBMP-2/ACS to allograft. In this study, efficacy of the treatment correlated with the ratio of rhBMP-2/ACS to allograft. As volume of rhBMP-2/ACS decreased below a 1:1 volume ratio, the overall efficacy decreased, thus indicating a potential limit to extending rhBMP-2/ACS past a 1:1 volumetric ratio in large segmental defects. Furthermore, ceramic was found to be a successful replacement for cancellous allograft bone at a 1:1 volumetric ratio. Clinical application using graft expanders or bone void fillers with rhBMP-2 should be used carefully and requires further investigation.