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Bony Reconstruction with rhBMP-2: Repair of Calvarial Defects Complicated by Radiation and Chronic Scar
Zoe MacIsaac, BA, Christopher R. Kinsella, Jr., MD, James J. Cray, Jr., PhD, Darren M. Smith, MD, S Alex Rottgers, MD, Harry Nayar, BA, Mark P. Mooney, PhD, Gregory M. Cooper, PhD, Joseph E. Losee, MD.
University of Pittsburgh, Pittsburgh, VA, USA.
PURPOSE: Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been shown to be an effective therapy in the acute calvarial defect wound. This modality is appealing in that donor site morbidity is eliminated and an unlimited supply of bone is theoretically available. This current study compares the effectiveness of rhBMP-2 in a more complicated calvarial defect to the gold standard of autologous repair.
METHODS: Nineteen adult New Zealand White rabbits (Group 1, Chronic Scar) underwent subtotal calvariectomy (15mm x 15mm), followed by 6 weeks of recovery and subsequent scar debridement with reconstruction with one of four treatments: empty control (no treatment, n=3), vehicle control (buffer solution on an absorbable collagen sponge (ACS), n=3), surgical control (cryopreserved autograft, n=3), and repair with rhBMP-2 (0.43 mg/ml rhBMP-2 on an ACS, n=10). In a second group (Group 2, Irradiation), seventeen adult New Zealand White rabbits underwent subtotal calvariectomy. Four days post-operatively, animals received 15 Gy to their calvarial defect. After six weeks of recovery, animals underwent scar debridement and received one of four therapies: empty control (n=3), vehicle control (n=2), surgical control (n=3), or repair with rhBMP-2 (n=9). Animals from both groups underwent CT imaging after definitive reconstruction at 0, 2, 4 and 6 weeks. At six weeks, animals were euthanized and defects examined histologically. Percent healing was determined by radiographic image analysis. A 4x3 mixed model ANOVA was performed on healing versus treatment group and postoperative time.
RESULTS: For Group 1, based on measures of radiopacity, treatment (rhBMP-2/ACS) and surgical control groups (autograft) were statistically equivalent, with 98% and 83% healing respectively at six weeks. Empty control and vehicle control groups, with 48% and 30% healing at six weeks, were inferior to the treatment (rhBMP-2/ACS) and surgical control (autograft) groups at each timepoint (p<0.05). For Group 2, based on measures of radiopacity, the treatment (rhBMP-2/ACS) and surgical control groups (autograft) were statistically equivalent with 99% and 89% healing respectively at six weeks. Empty control and vehicle control groups, with 35% and 34% healing at six weeks, were inferior to treatment (rhBMP-2/ACS) and surgical control (autograft) groups at each timepoint (p<0.05). Histologically, for both Group 1 and Group 2, bone in the surgical control (autograft) group was less trabecular and contained fewer cells compared to bone formed in the experimental treatment group (rhBMP-2/ACS).
CONCLUSION: Compared to controls, rhBMP-2/ACS therapy was as effective in reconstructing calvarial defects in unfavorable calvarial defects complicated by radiation and scarring. Compared to historical controls, bony regeneration with rhBMP-2 in complicated defects was as effective as in the acute, favorable calvarial wound. When compared to cryopreserved autograft, rhBMP-2-regenerated bone showed equal defect coverage and similar thickness with varying bony architecture. Further investigations are necessary to evaluate the long-term remodeling and to determine the biomechanical properties of bone generated as a result of rhBMP-2 treatment of complicated calvarial defects.
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