Synthesis and Preclinical Evaluation of a Novel Oxy133-Infused Biomimetic Bone Graft Using a Rat Model of Posterolateral Spinal Fusion.

OBJECTIVE

To 1) create a novel tissue-engineered bone graft comprising the osteoinductive oxysterol Oxy133 and 2) compare the osteogenic capability of this novel bone graft with bone graft substitutes previously examined.

METHODS

Oxy133 was homogeneously incorporated into a biomimetic (BioMim) bone graft substitute comprising extracellular matrix and calcium phosphates. Two iterations of the graft were created: one corresponding to an implant-dose of 2.0 mg Oxy133 (BioMim-Oxy133-Lo) and the other corresponding to an implant-dose of 20 mg Oxy133 (BioMim-Oxy133-Hi). Thirty-two male Sprague-Dawley rats were allocated randomly to 4 equally sized groups: 1) BioMim-Oxy133-Lo, 2) BioMim-Oxy133-Hi, 3) absorbable collagen sponge (ACS) with topically applied Oxy133 dissolved in dimethyl sulfoxide (ACS-Oxy133; 20 mg Oxy133/graft), and 4) ACS with topically applied recombinant human bone morphogenetic protein-2 (rhBMP-2) dissolved in water (ACS-rhBMP-2; 5.0 μg rhBMP-2/graft). All animals underwent L4-L5 posterolateral spinal fusion. Spines were harvested 8 weeks postoperatively and analyzed using micro-computed tomography imaging.

RESULTS

Successful fusion was achieved in all animals. Grafts containing Oxy133 had significantly greater bone volume, percent of bone volume per tissue volume (%BV), bone surface density (BSD), and trabecular number (TbN) compared to ACS-rhBMP-2 (P < 0.01 for each). Animals treated with BioMim-Oxy133-Lo had the greatest %BV, BSD, and TbN (P < 0.001 for each), whereas animals treated with ACS-rhBMP-2 had the lowest %BV, BSD, TbN, and trabecular thickness (P < 0.001 for each).

CONCLUSIONS

BioMim-Oxy133 is a novel bone graft that led to superior bone volume and quality compared to ACS-rhBMP-2 in a clinically translatable rat model of spinal fusion. Future work is needed to further evaluate this material as a safe and efficacious bone graft substitute.