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一种用于治疗骨髓炎的热不稳定抗生素洗脱 3D 打印支架的研制。

Development of a heat labile antibiotic eluting 3D printed scaffold for the treatment of osteomyelitis.

机构信息

Department of Molecular Medicine, College of Medicine, Gachon University, Incheon, Republic of Korea.

Department of Orthopedic Surgery, Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of Korea.

出版信息

Sci Rep. 2020 May 5;10(1):7554. doi: 10.1038/s41598-020-64573-5.

Abstract

In general, osteomyelitis is treated with antibiotics, and in severe cases, the inflammatory bone tissue is removed and substituted with poly (methyl methacrylate) (PMMA) beads containing antibiotics. However, this treatment necessitates re-surgery to remove the inserted PMMA beads. Moreover, rifampicin, a primary heat-sensitive antibiotic used for osteomyelitis, is deemed unsuitable in this strategy. Three-dimensional (3D) printing technology has gained popularity, as it facilitates the production of a patient-customized implantable structure using various biodegradable biomaterials as well as controlling printing temperature. Therefore, in this study, we developed a rifampicin-loaded 3D scaffold for the treatment of osteomyelitis using 3D printing and polycaprolactone (PCL), a biodegradable polymer that can be printed at low temperatures. We successfully fabricated rifampicin-loaded PCL 3D scaffolds connected with all pores using computer-aided design and manufacturing (CAD/CAM) and printed them at a temperature of 60 °C to prevent the loss of the antibacterial activity of rifampicin. The growth inhibitory activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), the representative causative organisms of osteomyelitis, was confirmed. In addition, we optimized the rifampicin-loading capacity that causes no damage to the normal bone tissues in 3D scaffold with toxicity evaluation using human osteoblasts. The rifampicin-releasing 3D scaffold developed herein opens new possibilities of the patient-customized treatment of osteomyelitis.

摘要

一般来说,骨髓炎采用抗生素治疗,在严重的情况下,去除炎症性骨组织并用含有抗生素的聚甲基丙烯酸甲酯 (PMMA) 珠粒替代。然而,这种治疗需要再次手术取出插入的 PMMA 珠粒。此外,利福平是一种主要的热敏抗生素,用于治疗骨髓炎,但在这种策略中并不适用。三维(3D)打印技术越来越受欢迎,因为它可以使用各种可生物降解的生物材料生产定制的植入式结构,并控制打印温度。因此,在这项研究中,我们使用 3D 打印和聚己内酯(PCL)开发了一种载利福平的 3D 支架,用于治疗骨髓炎,PCL 是一种可低温打印的可生物降解聚合物。我们成功地使用计算机辅助设计和制造(CAD/CAM)制造了连接所有孔的载利福平的 PCL 3D 支架,并将其在 60°C 的温度下打印,以防止利福平的抗菌活性丧失。证实了对大肠杆菌(E. coli)和金黄色葡萄球菌(S. aureus)的生长抑制活性,这两种细菌是骨髓炎的代表性致病生物。此外,我们使用人成骨细胞进行毒性评估,优化了不会对 3D 支架中的正常骨组织造成损害的载利福平容量。本文开发的载利福平 3D 支架为骨髓炎的个体化治疗开辟了新的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c723/7200676/2d9379ef0ad7/41598_2020_64573_Fig1_HTML.jpg

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