Rajkovic Christian J, Tracz Jovanna A, DeMordaunt Trevor, Davidar A Daniel, Perdomo-Pantoja Alexander, Judy Brendan F, Zhang Kevin Yang, Hernandez Vaughn N, Lin Jessica, Lazzari Julianna L, Cottrill Ethan, Witham Timothy F
Department of Neurosurgery, Johns Hopkins University School of Medicine, 1800 Orleans Street, Baltimore, MD 21287, United States.
Department of Neurosurgery, Washington University in St. Louis School of Medicine, 660 S. Euclid Avenue Campus Box 8057, St. Louis, MO 63110, United States.
N Am Spine Soc J. 2024 Apr 9;18:100323. doi: 10.1016/j.xnsj.2024.100323. eCollection 2024 Jun.
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 1×10 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.
术后感染是脊柱融合手术的一种并发症，会增加患者的发病率。已提出包括术中应用万古霉素粉末在内的策略来降低感染发生率；然而，这种抗菌效果是短暂的。
在30只大鼠中模拟椎弓根螺钉和棒固定进行L4-L5椎体的器械植入。在关闭创口前植入接种了PBS或1×10 CFU生物发光耐甲氧西林金黄色葡萄球菌（MRSA）的钛制器械，以及注入不同浓度万古霉素和125μg重组人骨形态发生蛋白-2（BioMim-rhBMP-2-VCM）的仿生骨移植材料。在术后六周内使用生物发光成像对感染进行定量。使用微型计算机断层扫描（micro-CT）评估关节融合情况。
接受注入低剂量（0.18mg/g）或高剂量万古霉素（0.89mg/g）骨移植材料的感染动物在术后六周内的生物发光信号均显著低于接种MRSA并植入不含万古霉素骨移植材料的对照动物（分别为p = 0.019和p = 0.007）。与对照动物相比，低剂量和高剂量万古霉素注入的骨移植材料在平均生物发光方面也均有统计学显著降低（分别为p = 0.027和p = 0.047），且与时间无关。对每组动物的micro-CT分析显示仅在对照组出现假关节，提示感染与假关节之间存在相关性。接种MRSA的对照动物在micro-CT上的骨体积形成也显著少于接种PBS的对照队列（p < 0.001）、MRSA + 低剂量万古霉素注入骨移植材料队列（p < 0.001）以及MRSA + 高剂量万古霉素注入骨移植材料队列（p < 0.001）。
BioMim-rhBMP-2-VCM提出了一种新的组织工程方法，可在脊柱融合中同时促进关节融合和抗菌预防。尽管文献中关于万古霉素潜在骨毒性的证据不一，但由于移植材料的骨诱导成分，BioMim-rhBMP-2-VCM随着万古霉素加载剂量的增加保留了关节融合和骨生成。
