Peptide Enhanced Bone Graft Substitute Presents Improved Short-Term Increase in Bone Volume and Construct Stiffness Compared to Iliac Crest Autologous Bone in an Ovine Lumbar Interbody Fusion Model

Arjan C Y Loenen, Jerome Connor, Scott Johnson, Katherine Davis, Nolan Hannigan, Tristan Barnes, Jacobus J Arts, Bert van Rietbergen, Arjan C Y Loenen, Jerome Connor, Scott Johnson, Katherine Davis, Nolan Hannigan, Tristan Barnes, Jacobus J Arts, Bert van Rietbergen

Abstract

Study design: Preclinical ovine model.

Objective: To assess the in vivo efficacy and safety of the P-15 L bone graft substitute and compare its performance to autologous iliac crest bone graft (ICBG) for lumbar interbody fusion indications.

Methods: Thirty skeletally mature sheep underwent lumbar interbody fusion surgery. Half of the sheep received autologous ICBG and the other half the peptide enhanced bone graft substitute (P-15 L). Following termination at 1, 3, and 6 months after surgery, the operated segments were analyzed using micro computed tomography (µCT), histology, and destructive mechanical testing. Additional systemic health monitoring was performed for the P-15 L group.

Results: One month after surgery, there was only minor evidence of bone remodeling and residual graft material could be clearly observed within the cage. There was active bone remodeling between 1 and 3 months after surgery. At 3 months after surgery significantly denser and stiffer bone was found in the P-15 L group, whereas at 6 months, P-15 L and ICBG gave similar fusion results. The P-15 L bone graft substitute did not have any adverse effects on systemic health.

Conclusions: The drug device combination P-15 L was demonstrated to be effective and save for lumbar interbody fusion as evidenced by this ovine model. Compared to autologous ICBG, P-15 L seems to expedite bone formation and remodeling but in the longer-term fusion results were similar.

Keywords: bone graft substitute; lumbar interbody fusion; morphological analysis; ovine; p-15 peptide.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Sagittal cut of the 3D rendered segmentation of a representative sample of the 1 month cohort. The regions excluded due to metal artifacts are greyed out. (a) The artifact-free region of the graft window in green and the unaffected cancellous bone reference regions in cyan. (b) Both regions of the graft window were exteriorly propagated to ensure a uniform height of 4 millimeters for the μFE analysis.
Figure 2.
Figure 2.
Sagittal μCT and histology cuts of both groups 1, 3, and 6 months after surgery. Residual P-15L graft can be recognized as hyper-opaque particles in μCT scans. For both groups, marker artifacts obscure the central region of the cage in the scans. Corresponding histological sections reveal there are no unexpected deviations in these artifact regions.
Figure 3.
Figure 3.
Changes over time in morphological parameters of the bone within the graft window and associated stiffness as determined by μFE. Time points marked with a star (*) indicate a significant difference between the P-15L and ICBG group. Morphological parameters of unaffected cancellous bone are shown as reference (REF). Abbreviations: BV/TV, bone volume over total volume; Tb.N, trabecular number; Tb.Th, trabecular thickness; Tb.Sp, trabecular separation; Conn.D, connectivity density.

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