Synthesis and evaluation of a novel vancomycin-infused, biomimetic bone graft using a rat model of spinal implant-associated infection

Christian J Rajkovic; Jovanna A Tracz; Trevor DeMordaunt; A Daniel Davidar; Alexander Perdomo-Pantoja; Brendan F Judy; Kevin Yang Zhang; Vaughn N Hernandez; Jessica Lin; Julianna L Lazzari; Ethan Cottrill; Timothy F Witham

doi:10.1016/j.xnsj.2024.100323

Synthesis and evaluation of a novel vancomycin-infused, biomimetic bone graft using a rat model of spinal implant-associated infection

N Am Spine Soc J. 2024 Apr 9:18:100323. doi: 10.1016/j.xnsj.2024.100323. eCollection 2024 Jun.

Affiliations

¹ Department of Neurosurgery, Johns Hopkins University School of Medicine, 1800 Orleans Street, Baltimore, MD 21287, United States.
² Department of Neurosurgery, Washington University in St. Louis School of Medicine, 660 S. Euclid Avenue Campus Box 8057, St. Louis, MO 63110, United States.
³ Department of Pathology, Johns Hopkins University School of Medicine, 1800 Orleans Street, Baltimore, MD 21287, United States.
⁴ Department of Orthopaedic Surgery, Duke University School of Medicine, DUMC Box 104002, Durham, NC 27710, United States.

Abstract

Background: Postoperative infection is a complication of spinal fusion surgery resulting in increased patient morbidity. Strategies including intraoperative application of powdered vancomycin have been proposed to reduce the incidence of infection; however, such antimicrobial effects are short-lived.

Methods: Instrumentation of the L4-L5 vertebrae was performed mimicking pedicle screw and rod fixation in 30 rats. Titanium instrumentation inoculated with either PBS or 1×10⁵ CFU bioluminescent MRSA, along with biomimetic bone grafts infused with varying concentrations of vancomycin and 125 µg of rhBMP-2 (BioMim-rhBMP-2-VCM) were implanted prior to closure. Infection was quantified during the six-week postoperative period using bioluminescent imaging. Arthrodesis was evaluated using micro-CT.

Results: Infected animals receiving a bone graft infused with low-dose (0.18 mg/g) or high-dose vancomycin (0.89 mg/g) both exhibited significantly lower bioluminescent signal over the six-week postoperative period than control animals inoculated with MRSA and implanted with bone grafts lacking vancomycin (p=.019 and p=.007, respectively). Both low and high-dose vancomycin-infused grafts also resulted in a statistically significant reduction in average bioluminescence when compared to control animals (p=.027 and p=.047, respectively), independent of time. MicroCT analysis of animals from each group revealed pseudoarthrosis only in the control group, suggesting a correlation between infection and pseudoarthrosis. MRSA-inoculated control animals also had significantly less bone volume formation on micro-CT than the PBS-inoculated control cohort (p<.001), the MRSA+low-dose vancomycin-infused bone graft cohort (p<.001), and the MRSA+high-dose vancomycin-infused bone graft cohort (p<.001).

Conclusion: BioMim-rhBMP-2-VCM presents a novel tissue engineering approach to simultaneously promoting arthrodesis and antimicrobial prophylaxis in spinal fusion. Despite mixed evidence of potential osteotoxicity of vancomycin reported in literature, BioMim-rhBMP-2-VCM preserved arthrodesis and osteogenesis with increasing vancomycin loading doses due to the graft's osteoinductive composition.

Keywords: Animal model; Antibiotic-infused graft; Bone graft; Implant-associated infection; Osteomyelitis; Spinal fusion; Spine infection.