Extremity Trauma and Regenerative Medicine Task Area, United States Army Institute of Surgical Research, 3698 Chambers Pass, JBSA Fort Sam Houston, TX 78234, USA.
Arteriocyte Medical Systems, Inc., 45 South St, Hopkinton, MA 01748, USA.
Spine J. 2017 Dec;17(12):1917-1925. doi: 10.1016/j.spinee.2017.06.039. Epub 2017 Jul 3.
Infections remain a leading complication associated with spinal arthrodesis, regardless of the use of prophylactic antibiotics and improved surgical techniques, with incidence of infection as high as 8.2%. Infection prolongs antibiotic usage, increases hospital time, and inevitably inflates overall treatment costs. Local antibiotics, such as vancomycin, have been used in combination with fusion materials over the past decade to decrease infection risk. An ideal graft material would serve a dual role: encouraging vertebral fusion while reducing the incidence of infection.
The objective of this study was to thoroughly evaluate the use of a vancomycin-loaded demineralized bone matrix (vDBM) for fusion capability while reducing the incidence of surgical site infection.
Antimicrobial efficacy and spinal fusion were evaluated using a preclinical rabbit model of posterolateral fusion.
Vancomycin-loaded demineralized bone matrix was prepared and evaluated for in vitro release kinetics and bacterial inhibition. In vivo antibacterial efficacy and fusion capability were performed using a model of posterolateral fusion in a rabbit. First, 10 New Zealand white rabbits underwent a bilateral posterolateral fusion procedure, were inoculated with Staphylococcus aureus, and were treated with either demineralized bone matrix (DBM) or vDBM. Fourteen days after the procedure, the animals were anesthetized and euthanized, and the transverse process was harvested and enumerated for bacterial quantification. Concurrently, 21 New Zealand white rabbits underwent the same procedure and were euthanized 8 weeks after surgery and were evaluated for fusion by manual palpation and radiographic scoring. In addition, two groups of six animals received the DBM or vDBM material as described, but the graft was combined with equal volumes of milled harvest iliac crest bone graft (ICBG). Eight weeks after surgery, these animals were euthanized and also evaluated for fusion by manual palpation and radiographic scoring.
Vancomycin continued to be released from the vDBM over the course of 6 days while maintaining sufficient eluate concentrations to maintain a zone of inhibition similar or larger than a vancomycin control. In vivo, vDBM significantly reduced the amount of bacteria within the fusion site compared with DBM, with a 4-log decrease in bacterial bioburden. The use of vDBM, however,showed a decrease in the fusion rate compared with DBM when used in a sterile wound. In a S. aureus-contaminated wound, both the DBM and the vDBM showed decreased fusion rates.Considering DBM materials were most commonly used as autograft extenders, additional animals received either DBM plus ICBG in a sterile wound or vDBM plus ICBG in a contaminated wound. Both groups had similar fusion rates and similar fusion volumes after 8 weeks in vivo.
Whereas vDBM reduced the overall bioburden within a contaminated surgical site of posterolateral fusion, the addition of the vancomycin to the DBM reduced the fusion capability of the DBM graft. The addition of ICBG to vDBM restored the fusion capability of the graft while reducing the overall infection.
无论是否使用预防性抗生素和改进的手术技术，感染仍然是与脊柱融合术相关的主要并发症，感染发生率高达 8.2%。感染会延长抗生素的使用时间，增加住院时间，并不可避免地增加整体治疗费用。局部抗生素，如万古霉素，在过去十年中已与融合材料联合使用，以降低感染风险。理想的移植物材料将起到双重作用：既能促进椎体融合，又能降低感染的发生率。
本研究旨在全面评估万古霉素负载脱钙骨基质（vDBM）在促进融合能力的同时降低手术部位感染发生率的应用。
使用兔后路融合的临床前模型评估抗生素的疗效和脊柱融合。
制备并评估万古霉素负载脱钙骨基质的体外释放动力学和抑菌效果。通过兔后路融合模型评估体内抗菌效果和融合能力。首先，10 只新西兰白兔进行双侧后路融合术，接种金黄色葡萄球菌，分别用脱钙骨基质（DBM）或 vDBM 治疗。术后 14 天，动物麻醉并安乐死，采集横突并进行细菌定量。同时，21 只新西兰白兔进行相同的手术，术后 8 周安乐死，通过手动触诊和放射学评分评估融合情况。此外，两组 6 只动物接受了上述 DBM 或 vDBM 材料，但移植物与等量磨碎的髂嵴骨移植物（ICBG）结合。术后 8 周，这些动物安乐死，并通过手动触诊和放射学评分评估融合情况。
万古霉素从 vDBM 中持续释放 6 天，同时保持足够的洗脱浓度，维持与万古霉素对照相似或更大的抑菌区。在体内，与 DBM 相比，vDBM 显著减少了融合部位的细菌数量，细菌生物负荷降低了 4 个对数级。然而，当在无菌伤口中使用时，vDBM 与 DBM 相比，融合率降低。在金黄色葡萄球菌污染的伤口中，DBM 和 vDBM 的融合率均降低。考虑到 DBM 材料最常用于自体移植物的扩展，另外一些动物在无菌伤口中接受 DBM 加 ICBG，或在污染伤口中接受 vDBM 加 ICBG。两组在体内 8 周后均具有相似的融合率和相似的融合体积。
虽然 vDBM 降低了后路融合术污染手术部位的总体生物负荷，但万古霉素的加入降低了 DBM 移植物的融合能力。将 ICBG 添加到 vDBM 中恢复了移植物的融合能力，同时降低了整体感染率。
