139 Development and Preclinical Evaluation of a Novel Oxy133-Infused Biomimetic Bone Graft using a Rat Model of Posterolateral Spinal Fusion

INTRODUCTION: Osteoinductive oxysterols present a promising small-molecule alternative to rhBMP-2 to promote bone formation. However, few reports have investigated the use of oxysterols when administered as an adjuvant in tissue-engineered bone grafts for spinal fusion. METHODS: Oxy133 was incorporated into a biomimetic bone graft substitute (BioMim) comprising extracellular matrix (ECM) and calcium phosphate; low-dose (2 mg Oxy133/graft, BioMim-Oxy133-Lo) and high-dose (20 mg Oxy133/graft, BioMim-Oxy133-Hi) formulations were produced. The grafts were evaluated using a rat model of L4-L5 posterolateral spinal fusion. ACS grafts with topically applied Oxy133 (20 mg/graft, ACS-Oxy133) or rhBMP-2 (5.0 µg/graft, ACS-rhBMP-2) were used as controls. Each experimental group consisted of eight animals (n=32) based on a priori power analysis. Spines were harvested eight weeks postoperatively and analyzed using microCT imaging, assessing the amount of formed bone volume (BV), percent of bone volume per tissue volume (%BV), bone surface area (BSA), bone surface density (BSD), trabecular size (TS), and trabecular number (TN). Successful spinal fusion was defined as continuous bridging bone across L4-L5 bilaterally. RESULTS: Successful spinal fusion was achieved in all animals. One-way ANOVA revealed a significant difference among the four groups for all quantitative outcomes (p<0.01 for each outcome). BioMim-Oxy133-Lo, ACS-Oxy133, and BioMim-Oxy133-Hi had significantly greater BV, %BV, BSD, and TN compared to ACS-rhBMP-2 (p<0.01 for each comparison). Animals treated with BioMim-Oxy133-Lo were found to have the greatest %BV, BSD, and TN (p<0.001 for each comparison). CONCLUSIONS: The Oxy133-infused biomimetic bone graft (BioMim-Oxy133) is a novel and promising bone graft substitute material.