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

Abstract

BackgroundPostoperative 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. MethodsInstrumentation 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. ResultsInfected 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 = 0.019 and p = 0.007, 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 = 0.027 and p = 0.047 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 < 0.001), the MRSA + low-dose vancomycin-infused bone graft cohort (p < 0.001), and the MRSA + high-dose vancomycin-infused bone graft cohort (p < 0.001). ConclusionBioMim-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.