Karlsruhe Institute of Technology (KIT), Institute of Functional Interfaces, 76344 Eggenstein-Leopoldshafen, Germany.
Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, German Red Cross Blood Service Baden-Württemberg - Hessen, Friedrich-Ebert Str. 107, 68167 Mannheim, Germany.
Acta Biomater. 2018 Jun;73:250-262. doi: 10.1016/j.actbio.2018.04.024. Epub 2018 Apr 19.
In this work, we define the requirements for a human cell-based osteomyelitis model which overcomes the limitations of state of the art animal models. Osteomyelitis is a severe and difficult to treat infection of the bone that develops rapidly, making it difficult to study in humans. We have developed a 3D in vitro model of the bone marrow, comprising a macroporous material, human hematopoietic stem and progenitor cells (HSPCs) and mesenchymal stromal cells (MSCs). Inclusion of biofilms grown on an implant into the model system allowed us to study the effects of postoperative osteomyelitis-inducing bacteria on the bone marrow. The bacteria influenced the myeloid differentiation of HSPCs as well as MSC cytokine expression and the MSC ability to support HSPC maintenance. In conclusion, we provide a new 3D in vitro model which meets all the requirements for investigating the impact of osteomyelitis.
Implant-associated osteomyelitis is a persistent bacterial infection of the bone which occurs in many implant patients and can result in functional impairments or even entire loss of the extremity. Nevertheless, surprisingly little is known on the triangle interaction between implant material, bacterial biofilm and affected bone tissue. Closing this gap of knowledge would be crucial for the fundamental understanding of the disease and the development of novel treatment strategies. For this purpose, we developed the first biomaterial-based system that is able to mimic implant-associated osteomyelitis outside of the body, thus, opening the avenue to study this fatal disease in the laboratory.
在这项工作中，我们定义了克服现有动物模型局限性的基于人细胞的骨髓炎模型的要求。骨髓炎是一种严重且难以治疗的骨骼感染，发展迅速，因此难以在人体中进行研究。我们开发了一种包含大孔材料、人类造血干细胞和祖细胞（HSPC）以及间充质基质细胞（MSC）的骨髓 3D 体外模型。将在植入物上生长的生物膜纳入模型系统，使我们能够研究术后引起骨髓炎的细菌对骨髓的影响。这些细菌影响 HSPC 的髓样分化以及 MSC 细胞因子表达和 MSC 维持 HSPC 的能力。总之，我们提供了一种新的 3D 体外模型，满足了研究骨髓炎影响的所有要求。
植入物相关骨髓炎是一种发生在许多植入物患者中的骨骼持续细菌感染，可能导致功能障碍甚至肢体完全丧失。尽管如此，人们对植入物材料、细菌生物膜和受影响的骨组织之间的三角相互作用知之甚少。填补这一知识空白对于深入了解疾病和开发新的治疗策略至关重要。为此，我们开发了第一个能够在体外模拟植入物相关骨髓炎的基于生物材料的系统，从而为在实验室中研究这种致命疾病开辟了道路。
