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延迟性细菌中性粒细胞募集与细菌在骨内扩散:人工关节周围感染发展中新发现的因素。来自成年小型猪模型的见解。

Delayed Bacterial Neutrophil Recruitment and Bacterial Bone Dispersion: New Identified Factors in Peri-Prosthetic Joint Infection Development. Insights From an Adult Minipig Model.

作者信息

Hartmann Katrine Top, Peterlin Anton Alexander Nolte, Hansen Marie Høy, Birch Julie Knippel Melsted, Odgaard Anders, Aalbæk Bent, Christensen Mads Holm, Thaarup Ida, Bjarnsholt Thomas, de Mesy Bentley Karen L, Petersen Andreas, Jensen Henrik Elvang, Jensen Louise Kruse

机构信息

Department of Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg C, Denmark.

Department of Orthopedics, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark.

出版信息

APMIS. 2025 Jun;133(6):e70031. doi: 10.1111/apm.70031.

Abstract

Clinically relevant animal models of peri-prosthetic joint infection (PJI) are essential for studying infection initiation and progression. This study developed a PJI model in adult Göttingen minipigs, explicitly focusing on the early stages of infection to gain new perceptions of PJI initiation. The model was established by drilling a hole into the femoral head, followed by inoculation with either Staphylococcus aureus (n = 6) or saline (n = 4) and inserting a stainless-steel screw. The animals were euthanized within 2 or 3 days post-inoculation. Comprehensive bone and joint pathology analyses were performed. All S. aureus inoculated animals had bacteria reisolated from bone, screw, synovial fluid, and synovial membrane. Histology revealed numerous bacterial colonies in the peri-implant bone tissue, many of which were unaccompanied by neutrophils, indicating delayed neutrophil recruitment to bacteria. In contrast, all synovial membrane-located bacteria were recognized by the immune system. Digital pathology measures showed deep bacterial dispersion within the bone, at a far distance from the point of inoculation. This study presents a new PJI model, which facilitates the investigation of infection initiation and supports studies aimed at preventing PJI. The study uncovered two previously unknown insights into the development of PJI: delayed bacterial neutrophil recruitment and widespread osseous bacterial dissemination within 48 h.

摘要

临床相关的人工关节周围感染(PJI)动物模型对于研究感染的起始和进展至关重要。本研究在成年哥廷根小型猪中建立了一种PJI模型,特别关注感染的早期阶段,以获得对PJI起始的新认识。该模型通过在股骨头钻孔,然后接种金黄色葡萄球菌(n = 6)或生理盐水(n = 4)并插入不锈钢螺钉来建立。在接种后2或3天内对动物实施安乐死。进行了全面的骨和关节病理学分析。所有接种金黄色葡萄球菌的动物的骨、螺钉、滑液和滑膜中均重新分离出细菌。组织学显示植入物周围骨组织中有大量细菌菌落,其中许多周围没有中性粒细胞,表明中性粒细胞向细菌的募集延迟。相比之下,所有位于滑膜的细菌都被免疫系统识别。数字病理学测量显示细菌在骨内深度扩散,距离接种点很远。本研究提出了一种新的PJI模型,该模型有助于研究感染的起始,并支持旨在预防PJI的研究。该研究揭示了关于PJI发展的两个先前未知的见解:细菌中性粒细胞募集延迟和48小时内骨内细菌广泛播散。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2075/12138841/cdf42fd8d29a/APM-133-0-g003.jpg

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