在骨科植入物相关感染的兔模型中进行体内生物发光成像，以监测释放抗生素涂层的疗效。
In Vivo Bioluminescence Imaging in a Rabbit Model of Orthopaedic Implant-Associated Infection to Monitor Efficacy of an Antibiotic-Releasing Coating.
机构信息
Departments of Dermatology (R.J.M., M.C.M., N.K.A., B.L.P., R.V.O., I.D.B., Y.W., and L.S.M.) and Orthopaedic Surgery (J.M.T., R.S.S., and L.S.M.) and Division of Infectious Diseases, Department of Medicine (L.S.M.), Johns Hopkins University School of Medicine, Baltimore, Maryland.
Departments of Biomedical Engineering (J.Z.) and Materials Science and Engineering (X.J., R.A.M., H.-Q.M., and L.S.M.), Translational Tissue Engineering Center (X.J., R.A.M., H.-Q.M., and L.S.M.), Institute for NanoBioTechnology (X.J., R.A.M., and H.-Q.M.), and Whitaker Biomedical Engineering Institute (H.-Q.M.), Johns Hopkins University, Baltimore, Maryland.
出版信息
J Bone Joint Surg Am. 2019 Feb 20;101(4):e12. doi: 10.2106/JBJS.18.00425.
BACKGROUND
In vivo bioluminescence imaging (BLI) provides noninvasive monitoring of bacterial burden in animal models of orthopaedic implant-associated infection (OIAI). However, technical limitations have limited its use to mouse and rat models of OIAI. The goal of this study was to develop a larger, rabbit model of OIAI using in vivo BLI to evaluate the efficacy of an antibiotic-releasing implant coating.
METHODS
A nanofiber coating loaded with or without linezolid-rifampin was electrospun onto a surgical-grade locking peg. To model OIAI in rabbits, a medial parapatellar arthrotomy was performed to ream the femoral canal, and a bright bioluminescent methicillin-resistant Staphylococcus aureus (MRSA) strain was inoculated into the canal, followed by retrograde insertion of the coated implant flush with the articular surface. In vivo BLI signals were confirmed by ex vivo colony-forming units (CFUs) from tissue, bone, and implant specimens.
RESULTS
In this rabbit model of OIAI (n = 6 rabbits per group), implants coated without antibiotics were associated with significantly increased knee width and in vivo BLI signals compared with implants coated with linezolid-rifampin (p < 0.001 and p < 0.05, respectively). On day 7, the implants without antibiotics were associated with significantly increased CFUs from tissue (mean [and standard error of the mean], 1.4 × 10 ± 2.1 × 10 CFUs; p < 0.001), bone (6.9 × 10 ± 3.1 × 10 CFUs; p < 0.05), and implant (5.1 × 10 ± 2.2 × 10 CFUs; p < 0.05) specimens compared with implants with linezolid-rifampin, which demonstrated no detectable CFUs from any source.
CONCLUSIONS
By combining a bright bioluminescent MRSA strain with modified techniques, in vivo BLI in a rabbit model of OIAI demonstrated the efficacy of an antibiotic-releasing coating.
CLINICAL RELEVANCE
The new capability of in vivo BLI for noninvasive monitoring of bacterial burden in larger-animal models of OIAI may have important preclinical relevance.
背景
活体生物发光成像（BLI）可在骨科植入物相关感染（OIAI）的动物模型中进行非侵入性细菌载量监测。然而，技术限制使其仅能应用于 OIAI 的小鼠和大鼠模型。本研究的目的是通过活体 BLI 开发一种更大的兔 OIAI 模型，以评估抗生素释放植入物涂层的疗效。
方法
将载有或不载利奈唑胺-利福平的纳米纤维涂层电纺到外科级锁定钉上。为了在兔中建立 OIAI 模型，通过内侧髌旁关节切开术扩髓股骨管，并将发光的耐甲氧西林金黄色葡萄球菌（MRSA）菌株逆行插入管腔，然后将涂层植入物平齐关节表面逆行插入。通过组织、骨骼和植入物标本的体外集落形成单位（CFU）确认活体 BLI 信号。
结果
在本兔 OIAI 模型中（每组 6 只兔），与载有利奈唑胺-利福平的植入物相比，未涂抗生素的植入物与膝关节宽度增加和活体 BLI 信号显著相关（分别为 p < 0.001 和 p < 0.05）。在第 7 天，未涂抗生素的植入物与组织（平均[和均方误差]，1.4×10±2.1×10 CFU；p < 0.001）、骨骼（6.9×10±3.1×10 CFU；p < 0.05）和植入物（5.1×10±2.2×10 CFU；p < 0.05）标本中的 CFU 显著增加，而载有利奈唑胺-利福平的植入物在任何来源中均未检测到 CFU。
结论
通过将发光的耐甲氧西林金黄色葡萄球菌菌株与改良技术相结合，在兔 OIAI 模型中进行活体 BLI 可证明抗生素释放涂层的疗效。
临床相关性
在 OIAI 的大动物模型中，活体 BLI 进行非侵入性细菌载量监测的新能力可能具有重要的临床前相关性。
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