Cyclic-RGD Is as Effective as rhBMP-2 in Anterior Interbody Fusion of the Sheep Cervical Spine

Abstract

Radiological and histological assessment of fusion status after anterior cervical discectomy and fusion (ACDF) procedure in a sheep spinal fusion model. To evaluate the efficacy of cyclic arginine-glycine-aspartic (cRGD) in comparison with recombinant human bone morphogenetic protein-2 (rhBMP-2) on a mineralized collagen matrix (MCM). A previous evaluation of MCM alone in comparison with autologous bone graft alone was not able to show an advantage on spinal fusion. The cRGD peptide sequence plays a major role in mediating cell adhesion. Studies have demonstrated enhances osteoblasts adhesion resulting in increased periimplant bone formation after implantcoating with cRGD. rhBMP-2 has already proven its ability to enhance spinal fusion. To date, no comparative in vivo evaluation of cRGD and rhBMP-2 in combination with a MCM for spinal fusion has been performed. Twenty-four sheep (N = 8/group) underwent C3-C4 fusion. Implants: group 1: titanium cage with MCM and rhBMP-2; group 2: titanium cage with MCM and cRGD; control group: titanium cage with MCM alone. After 12 weeks fusion sites were evaluated by computed tomography to assess fusion status, bone mineral density as well as bony callus volume. Furthermore, histomorphological and histomorphometrical analysis of the fusion sites were performed. In comparison with the control group, cRGD, and rhBMP-2 groups showed a higher fusion rate in radiographical findings and a higher degree of interbody fusion in histomorphometrical analysis (P < 0.05). There was no significant difference in radiographical and histological parameters between the rhBMP-2 and the cRGD group. Although rhBMP-2 demonstrated ectopic prevertebral bone formations, this effect was less prominent in the cRGD group. In this animal model the combination of cRGD and a mineralized collagen matrix showed superior fusion results in comparison with the mineralized collagen alone. Further, cRGD was comparably effective to rhBMP-2 in promoting interbody fusion by demonstrating less ectopic bone formations.