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

• DOI: 10.1016/j.xnsj.2024.100323
• Publication Date: 2024-04-09T15:49:51Z
• Authors: Christian J. Rajk...; Jovanna A. Tracz; Trevor DeMordaunt; A. Daniel Davidar; Alexander Perdomo...; Brendan F. Judy; Kevin Yang Zhang; Vaughn N. Hernandez; Jessica Lin; Julianna L. Lazzari; Ethan Cottrill; Timothy F. Witham
• Keywords: Orthopedic surgery; Implant-associated infection; Osteomyelitis; Antibiotic-infused graft; 03 medical and health sciences; 0302 clinical medicine; Basic Science; Bone graft; Animal model; Spinal fusion; Neurology. Diseases of the nervous system; RC346-429; RD701-811

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.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.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).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.