Acceleration of spinal fusion using COMP-angiopoietin 1 with allografting in a rat model

Abstract

Introduction: Allografting has become widely available for the elimination of morbidity due to autogenous bone grafting procedures for spinal fusion. Enhancement of stable bone formation could facilitate this procedure. COMP-Ang1 is a recombinant chimeric protein of angiopoietin-1 that induces angiogenesis and vascular enlargement. We investigated the osteogenic potential of COMP-Ang1 for spinal fusion with allograft based on the enhancement of angiogenesis. Methods: Sixty Sprague-Dawley rats underwent bilateral posterior and posterolateral arthrodesis with allograft at L3-4 and L4-5. The animals were divided into three groups (n = 20 each): 1) no treatment (sham group); 2) the bovine serum albumin-impregnated collagen sponge group (BSA group); 3) the COMP-Ang1-impregnated collagen sponge group (COMP-Ang1 group). Animals were sacrificed at six weeks for evaluation of spinal fusion using manual palpation, radiographs, and biomechanical and histomorphometric assessments. Total RNA was prepared from the fusion site and analyzed for osteogenic marker protein expression using RT-PCR analysis. Results: The fusion rates determined by manual palpation were 38.9% in the sham group, 42.1% in the BSA group, and 89.5% in the COMP-Ang1 group. Optical density of fusion masses in the COMP-Ang1 group was significantly higher than those in the sham and BSA groups (p<0.001). Total bone volume was significantly higher in the COMP-Ang1 group than in the sham and BSA groups (p<0.001). The mechanical strength was significantly greater in the COMP-Ang1 group than in the sham and BSA groups (p<0.01). Histologically, the fusion site of the COMP-Ang1 group showed a larger number of reactive bones compared with those in the BSA and sham groups. Immunostaining of endothelial cells for factor VIII revealed that COMP-Ang1 group showed higher levels of vascularity in the fusion site. Runt-related transcription factor 2 and its target genes were significantly up-regulated in the COMP-Ang1 group. Conclusions: COMP-Ang1 induced radiologically and histologically demonstrable active osteogenesis by promoting angiogenesis in spinal fusions. It was concluded that COMP-Ang1 enhances spinal fusion and hence the strength of the fusion. (C) 2011 Elsevier Inc. All rights reserved.