G.E.R.N. Research Center for Tissue Replacement, Regeneration and Neogenesis, Department of Orthopedics and Trauma Surgery, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Medical Center-Albert-Ludwigs-University of Freiburg, Engesserstr. 4, Freiburg im Breisgau 79108, Germany.
G.E.R.N. Research Center for Tissue Replacement, Regeneration and Neogenesis, Department of Orthopedics and Trauma Surgery, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Medical Center-Albert-Ludwigs-University of Freiburg, Engesserstr. 4, Freiburg im Breisgau 79108, Germany.
Acta Biomater. 2022 May;144:230-241. doi: 10.1016/j.actbio.2022.03.020. Epub 2022 Mar 15.
The aim of this work was to establish an organ model for staphylococcal infection of human bone samples and to investigate the influence and efficacy of a microporous β-tricalcium phosphate ceramic (β-TCP, RMS Foundation) loaded with hydrogels (alginate, alginate-di-aldehyde (ADA)-gelatin) and clindamycin on infected human bone tissue over a period of 28 days. For this purpose, human tibia plateaus, collected during total knee replacement surgery, were used as a source of bone material. Samples were infected with S. aureus ATCC29213 and treated with differently loaded β-TCP composites (alginate +/- clindamycin, ADA-gelatin +/- clindamycin, unloaded). The loading of the composites was carried out by means of a flow chamber. The infection was observed for 28 days, quantifying bacteria in the medium and the osseus material on day 1, 7, 14, 21 and 28. All samples were histologically processed for bone vitality evaluation. Bone infection could be consistently performed within the organ model. In addition, a strong reduction in bacterial counts was recorded in the groups treated with ADA-gelatin + clindamycin and alginate + clindamycin, while the bacterial count in the control groups remained constant. No significant differences between groups could be observed in the number of lacunae filled with osteocytes suggesting no differences in bone vitality among groups. In an ex-vivo human bone infection model, over a period of 28 days bacterial growth could be reduced by treatment with ADA-Gel + CLI and ALG + CLI -releasing β-TCP composites. This could be relevant for its clinical use. Further work will be necessary to improve the loading of β-TCP and the bone infection organ model itself. STATEMENT OF SIGNIFICANCE: The common treatment of bone infections is debridement and systemic administration of antibiotics. In some cases, antibiotic-containing carriers are already used, but these must be removed again. Our work is intended to show another treatment option. The scaffold we have developed, made of a calcium phosphate ceramic and a hydrogel as the active substance carrier, can, in addition to releasing the active substance, also assume a load-bearing function of the bone and is biodegradable. In addition, the model we developed can also be used for the analysis and treatment of bone infections other than those of the musculoskeletal system. More importantly, it can also serve as a substitute for previously used animal experiments.
本工作旨在建立一种用于研究金黄色葡萄球菌感染人骨样本的器官模型,并探讨载有透明质酸凝胶(alginate)、透明质酸-乙二醛(ADA)-明胶(gelatin)和克林霉素的微孔 β-磷酸三钙陶瓷(β-TCP,RMS Foundation)对感染人骨组织的影响和疗效,为期 28 天。为此,我们使用在全膝关节置换术中收集的人胫骨平台作为骨材料的来源。样本被金黄色葡萄球菌 ATCC29213 感染,并分别用不同负载β-TCP 复合材料(alginate +/- 克林霉素、ADA-明胶 +/- 克林霉素、未负载)进行处理。复合材料的负载是通过流室进行的。在第 1、7、14、21 和 28 天观察感染情况,定量分析培养基和骨质材料中的细菌。所有样本均进行组织学处理,以评估骨活力。在器官模型中可以持续进行骨感染。此外,在用 ADA-明胶+克林霉素和透明质酸+克林霉素处理的组中,细菌计数明显减少,而对照组中的细菌计数保持不变。各组间成骨细胞填充的腔隙数量无显著差异,提示各组间骨活力无差异。在为期 28 天的体外人骨感染模型中,用 ADA-Gel+CLI 和 ALG+CLI 释放的β-TCP 复合材料处理可减少细菌生长。这对于其临床应用可能具有重要意义。需要进一步的工作来改进β-TCP 的负载和骨感染器官模型本身。 意义声明:骨感染的常见治疗方法是清创和全身应用抗生素。在某些情况下,已经使用了载有抗生素的载体,但这些载体必须再次取出。我们的工作旨在展示另一种治疗选择。我们开发的支架由磷酸钙陶瓷和水凝胶作为活性物质载体组成,除了释放活性物质外,还可以承担骨骼的承重功能,并且可生物降解。此外,我们开发的模型还可用于分析和治疗除肌肉骨骼系统以外的骨感染。更重要的是,它还可以替代以前使用的动物实验。
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