Novel Animal Model of Calvarial Defect

Abstract

Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been shown to be an effective therapy in the acute calvarial defect wound and in calvarial defects complicated by chronic scar and radiation. The authors assessed the effectiveness of rhBMP-2-mediated bone regeneration in calvarial defects complicated by durectomy. Sixteen adult New Zealand White rabbits underwent subtotal calvariectomy and dural removal, followed by dural repair and reconstruction in one of four groups: empty (n = 3), vehicle (buffer solution on an absorbable collagen sponge, n = 2), autologous graft (n = 3), or rhBMP-2 repair (rhBMP-2/absorbable collagen sponge, n = 8). Animals underwent computed tomographic imaging at 0, 2, 4, and 6 weeks postoperatively, followed by euthanasia and histologic analysis. Percent healing was determined by three-dimensional analysis. A 4 × 3 mixed model analysis of variance was performed on healing versus treatment group/postoperative time. The rhBMP-2/absorbable collagen sponge and autograft repair groups had 51.4 and 37.3 percent healing, respectively, at 6 weeks; empty and vehicle control groups had 7.8 and 17.9 percent healing, respectively, at 6 weeks. Compared with immediate favorable reconstruction (96.8 percent healing), rhBMP-2 in this setting was significantly less effective (p = 0.001). Bone in the rhBMP-2/absorbable collagen sponge group was compact and cellular but appeared only over the intact sagittal sinus and irregularly within the absorbable collagen sponge. Although promising in the acute calvarial wound and other complex defects, rhBMP-2 therapy is less effective in reconstruction following dural compromise. Future studies using additional growth factors and cell therapy may improve results in this especially difficult scenario.