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Updated: Jun 5, 2025
Use of Human Perivascular Stem Cells for Bone Regeneration
Published on: May 25, 2012
Synthesis and Preclinical Evaluation of a Novel Oxy133-Infused Biomimetic Bone Graft Using a Rat Model of
Ethan Cottrill1, Christian J Rajkovic2, Jessica Lin2
1The Spinal Fusion Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Department of Orthopedic Surgery, Duke University School of Medicine, Durham, North Carolina, USA.
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.
