Comparison of synthetic bone graft ABM/P-15 and allograft on uninstrumented posterior lumbar spine fusion in sheep

Abstract

Background: Spinal fusion is a commonly used procedure in spinal surgery. To ensure stable fusion, bone graft materials are used. ABM/P-15 (commercial name i-Factor™ Flex) is an available synthetic bone graft material that has CE approval in Europe. This peptide has been shown to improve bone formation when used in devices with fixation or on bone defects. However, the lack of external stability and large graft size make posterolateral lumbar fusion (PLF) a most challenging grafting procedure. This prospective randomized study was designed to evaluate early spinal fusion rates using an anorganic bovine-derived hydroxyapatite matrix (ABM) combined with a synthetic 15 amino acid sequence (P-15)-ABM/P-15 bone graft, and compared with allograft in an uninstrumented PLF model in sheep. The objective of this study was to assess fusion rates when using ABM/P-15 in uninstrumented posterolateral fusion in sheep.

Methods: Twelve Texas/Gotland mixed breed sheep underwent open PLF at 2 levels L2/L3 and L4/L5 without fixation instruments. The levels were randomized so that sheep received an ABM graft either with or without P15 coating. Sheep were euthanized after 4.5 months and levels were harvested and evaluated with a micro-CT scanner and qualitative histology. Fusion rates were assessed by 2D sections and 3D reconstruction images and fusion was defined as intertransverse bridging.

Results: There was 68% fusion rate in the allograft group and an extensive migration of graft material was noticed with a fusion rate of just 37% in the ABM/P-15 group. Qualitative histology showed positive osteointegration of the material and good correlation to scanning results.

Conclusions: In this PLF fusion model, ABM/P15 demonstrated the ability to migrate when lacking external stability. Due to this migration, reported fusion rates were significantly lower than in the allograft group. The use of ABM/P15 as i-Factor™ Flex may be limited to devices with fixation and bone defects.

Keywords: ABM/P-15; Histology; Micro-CT; Posterolateral spinal fusion; Sheep.

Conflict of interest statement

Ethics approval and consent to participate

The Danish Animal Experiments and Inspectorates approved this study (2011/561–195) and all experimental procedures were performed in accordance with ARRIVE guidelines and the Danish Animal Research guidelines.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1

Micro-CT images showed different bone formation patterns: allograft had nice bone formation with a combination of woven and lamellar bones. ABM/P-15 also displayed nice bone formation with clearly visible unresolved residue of hydroxyapatite. Upper left: 2D section of allograft (circle), and upper right: 3D reconstruction of allograft fusion mass. Lower left: 2D section of ABM/P-15 (circle). Upper right: 3D reconstruction of ABM/P-15 fusion mass

Fig. 2

A photo of a migration of ABM/P-15 (blue circle): In this case, migration was ventrally and caudally situated on frontal side of the transverse processes

Fig. 3

Qualitative histology of fusion section with Toluidine blue 0.1% staining illustrated transition two zones. a Proximal transition zone from transverse process (lower-right part) to graft material (upper-left part) is illustrated: cortical bone has typical laminar structure and Haversian canals (H), and ABM granule (G) is surrounded by woven bone. b Distal transition zone from graft material (lower-right part) to fibrous tissue (lower-left) in non-fused mass with a clear gap in between. c Good osteointegration. Hydroxyapatite granule surrounded by woven bone. No foreign body giant cells