Preclinical Evaluation of Synthetic Bone Graft Materials in an Instrumented Sheep Posterolateral Lumbar Spinal Fusion Model.

Abstract

This study conducted a multi-endpoint analysis of synthetic bone grafts used as standalone in a clinically relevant instrumented sheep PLF model. The objective was to evaluate the efficacy of commercially available synthetic bone grafts when used as standalone in a state-of-the-art instrumented sheep PLF model. The performance was measured using a comprehensive range of assessment tools. The amount of (pre)clinical data on the quality of spinal fusions using synthetic bone grafts is limited. Recently, a biphasic CaP with a needle-shaped submicron surface topography has demonstrated enhanced bone-forming ability driven by its surface structure triggering a favorable biological response from the innate immune system. Six sheep underwent instrumented PLF surgery using the following bone grafts as standalone: (1) biphasic CaP with a needle-shaped submicron surface topography embedded in a collagen matrix (BCP<µm), (2) anorganic bone mineral with a synthetic peptide sequence in a hydrogel carrier (ABM/P15), (3) silicate-substituted CaP in a hydrogel carrier (nSiCaP), and (4) 45S5 Bioglass embedded in a collagen matrix (BG). After 12 weeks, spinal fusion was determined by manual palpation, radiograph and µCT imaging, range-of-motion mechanical testing, and histologic and histomorphologic evaluation. Radiography and µCT demonstrated superior fusion rates for BCP<µm compared with all other groups. Histology revealed significant graft resorption complemented by abundant bone tissue and continuous bony bridging between TPs in 3/3 implants for BCP<µm compared with only 1/3 implants for nSiCaP and 0/3 implants for ABM/P15 and BG. Histomorphometrical analysis, showed BCP<µm having the greatest new bone formation at 53±2.2%. These results show distinct differences in the performance between commercially available bone graft substitutes, highlighting the importance of utilizing clinically relevant animal models with robust, multi-endpoint analyses to evaluate their efficacy. Specifically, BCP<µm achieved superior fusion rates compared with other synthetic bone grafts when used standalone, further demonstrating its enhanced bone-forming ability in vivo.