Abstract：
Osteomyelitis is a pathological condition of the bone, frequently associated with the presence of infectious agents - namely Staphylococcus aureus - that induce inflammation and tissue destruction. Recent advances in the understanding of its pathophysiology and the identification of innovative therapeutic approaches were gathered from experimental in vitro and in vivo systems. However, cell culture models offer limited representativeness of the cellular functionality and the cell-cell and cell-matrix interactions, further failing to mimic the three-dimensional tissue organization; and animal models allow for limited mechanistic assessment given the complex nature of systemic and paracrine regulatory systems and are endorsed with ethical constraints. Accordingly, this study aims at the establishment and assessment of a new ex vivo bone infection model, upon the organotypic culture of embryonic chicken femurs colonized with S. aureus, highlighting the model responsiveness at the molecular, cellular, and tissue levels. Upon infection with distinct bacterial inoculums, data reported an initial exponential bacterial growth, followed by diminished metabolic activity. At the tissue level, evidence of S. aureus-mediated tissue destruction was attained and demonstrated through distinct methodologies, conjoined with decreased osteoblastic/osteogenic and increased osteoclastic/osteoclastogenic functionalities-representative of the osteomyelitis clinical course. Overall, the establishment and characterization of an innovative bone tissue infection model that is simple, reproducible, easily manipulated, cost-effective, and simulates many features of human osteomyelitis, further allowing the maintenance of the bone tissue\'s three-dimensional morphology and cellular arrangement, was achieved. Model responsiveness was further demonstrated, showcasing the capability to improve the research pipeline in bone tissue infection-related research.
摘要：
骨髓炎是骨骼的病理状况，经常与感染因子的存在有关-即金黄色葡萄球菌-诱导炎症和组织破坏。从体外和体内实验系统中收集了对其病理生理学的理解和创新治疗方法的鉴定的最新进展。然而,细胞培养模型对细胞功能以及细胞-细胞和细胞-基质相互作用的代表性有限，进一步未能模拟三维组织组织;考虑到系统和旁分泌调节系统的复杂性质，动物模型允许有限的机制评估，并得到伦理约束的认可。因此，本研究旨在建立和评估一种新的离体骨感染模型，在金黄色葡萄球菌定植的胚胎鸡股骨的器官型培养后，突出分子的模型响应性，细胞，和组织水平。感染不同的细菌接种物后，数据报告了最初的细菌指数生长，其次是代谢活动减少。在组织层面,通过不同的方法获得并证明了金黄色葡萄球菌介导的组织破坏的证据，伴随着成骨细胞/成骨功能降低和破骨细胞/破骨细胞功能增加-代表骨髓炎临床病程。总的来说,简单的创新骨组织感染模型的建立和表征，可重复,容易被操纵,成本效益高,模拟人类骨髓炎的许多特征，进一步允许维持骨组织的三维形态和细胞排列，已实现。进一步证明了模型响应性，展示改善骨组织感染相关研究的研究管道的能力。
