Synthesis and preclinical evaluation of a novel Oxy133-infused biomimetic bone graft using a rat model of posterolateral spinal fusion

Ethan Cottrill; Christian J Rajkovic; Jessica Lin; Mahnoor Shafi; Jovanna A Tracz; Vaughn Hernandez; Farhad Parhami; Timothy F Witham

doi:10.1016/j.wneu.2024.12.010

Synthesis and preclinical evaluation of a novel Oxy133-infused biomimetic bone graft using a rat model of posterolateral spinal fusion

World Neurosurg. 2024 Dec 7:S1878-8750(24)02001-1. doi: 10.1016/j.wneu.2024.12.010. Online ahead of print.

Authors

Ethan Cottrill¹, Christian J Rajkovic², Jessica Lin², Mahnoor Shafi², Jovanna A Tracz², Vaughn Hernandez², Farhad Parhami³, Timothy F Witham²

Affiliations

¹ The 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. Electronic address: ethan.cottrill@duke.edu.
² The Spinal Fusion Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
³ MAX BioPharma, Inc., Santa Monica, California, USA.

PMID: 39653079
DOI: 10.1016/j.wneu.2024.12.010

Abstract

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 bone graft substitute (BioMim) comprising extracellular matrix and calcium phosphates. Two iterations of the graft were created: one corresponding to an implant-dose of 2.0mg Oxy133 (BioMim-Oxy133-Lo) and the other corresponding to an implant-dose of 20mg Oxy133 (BioMim-Oxy133-Hi). Thirty-two male Sprague Dawley rats were allocated randomly to four 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; 20mg Oxy133/graft), and 4) ACS with topically applied rhBMP-2 dissolved in water (ACS-rhBMP-2; 5.0μg rhBMP-2/graft). All animals underwent L4-L5 posterolateral spinal fusion. Spines were harvested 8 weeks postoperatively and analyzed using micro-CT imaging.

Results: Successful fusion was achieved in all animals. Grafts containing Oxy133 had significantly greater bone volume, percentage bone 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.

Keywords: animal models; biomaterials; bone grafts; bone tissue engineering; oxysterol; spinal fusion.