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Novel Animal Model of Calvarial Defect Part II: Reconstruction of an Unfavorable Scarred Wound with rhBMP-2
Christopher R. Kinsella, Jr., MD, James J. Cray, PhD, Darren M. Smith, MD, S. Alex Rottgers, MD, Mark M. Mooney, PhD, Gregory M. Cooper, PhD, Joseph E. Losee, MD.
University of Pittsburgh, Pittsburgh, PA, USA.

BACKGROUND: Animal models of bone reconstruction have shown recombinant human bone morphogenetic protein-2 (rhBMP-2) to be an effective therapy in the acute calvarial defect wound. The purpose of this study is to compare the effectiveness of rhBMP-2 in a rabbit model of an unfavorable scarred calvarial wound with the gold standard of autograft.
METHODS: Nineteen adult New Zealand White rabbits underwent subtotal calvariectomy. After six weeks of healing and normal scar formation, these animals underwent reoperation for scar debridement and assignment to one of four therapeutic groups. Animals were assigned to an empty control group (no treatment, n=3), vehicle control group (neutral buffered solution (NBS) on an absorbable collagen sponge (ACS), n=3), surgical control group (cryopreserved autograft, n=3), or an experimental treatment group (rhBMP-2 on an ACS, n=10). All animals underwent CT imaging at 0, 2, 4 and 6 weeks post secondary reconstructive surgery. At six weeks, all animals were euthanized and the defects were examined histologically. Percent healing of each defect was determined and a 4x3 mixed model ANOVA was performed on healing as a function of time and therapy.
RESULTS: Based on measures of defect radiopacity, the treatment group (rhBMP-2/ACS) and surgical control group (autograft) were statistically equivalent with 98% and 83% healing respectively at six weeks. The empty control and vehicle control groups were inferior to the treatment group (rhBMP-2/ACS) and surgical control (autograft) groups at each timepoint (p<0.05). Histologically, bone in the surgical control (autograft) group was less trabecular and less cellular than the bone formed in the experimental treatment group (rhBMP-2/ACS).
CONCLUSIONS: Compared to historical controls, rhBMP-2 therapy was as effective in reconstructing calvarial defects in the unfavorable scarred wound as in the acute favorable calvarial wound. When compared to cryopreserved autograft, rhBMP-2-regenerated bone showed equal defect coverage and similar bone thickness with varying boney architecture.


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