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用于治疗创伤性骨髓炎的双抗生素聚乳酸-羟基乙酸共聚物微球

Dual antibiotic PLGA microspheres for the treatment of traumatic osteomyelitis.

作者信息

Si Liangguo, Zhang Wenping, Jiang Haifeng, Ma Haiqiang, Ma Xu, Zhao Peijie, Sun Huanhuan, Yang Zhipeng, Qiao Zewen

机构信息

School of Clinical Medicine, Ningxia Medical University , 750004, Yinchuan, China.

General Hospital of Ningxia Medical University, 750004, Yinchuan, China.

出版信息

Sci Rep. 2025 Aug 21;15(1):30694. doi: 10.1038/s41598-025-14824-0.

DOI:10.1038/s41598-025-14824-0
PMID:40841735
Abstract

Traumatic osteomyelitis (TO) treatment remains challenging due to biofilm formation and poor antibiotic penetration. We developed poly(lactic-co-glycolic acid) (PLGA) microspheres co-loaded with moxifloxacin/rifampicin (M/R-P) to address these limitations. Key findings: In vitro: The microspheres showed (1) no cytotoxicity (CCK-8 assay; live/dead staining; cytoskeletal staining; SEM visualization), and (2) no inhibition of osteogenic potential (ALP activity).In vivo: M/R-P microspheres significantly reduced MRSA burden ( 8 ± 3 × 10³ CFU/g) compared to debridement-only controls (3143 ± 727 × 10³ CFU/g; p < 0.0001), and near-complete infection resolution (histopathology). Conclusion: These results demonstrate that the M/R-P microspheres possess excellent safety profiles, favorable cytocompatibility, and remarkable antibacterial efficacy. The findings confirm the feasibility of our innovative approach using PLGA as a drug delivery carrier for localized antibiotic therapy in chronic osteomyelitis treatment, achieved through technological optimization for combined antibiotic administration. This provides a novel strategic direction for ultimately overcoming the clinical challenge of traumatic osteomyelitis.

摘要

由于生物膜形成和抗生素渗透性差,创伤性骨髓炎(TO)的治疗仍然具有挑战性。我们开发了载有莫西沙星/利福平(M/R-P)的聚乳酸-羟基乙酸共聚物(PLGA)微球来解决这些局限性。主要发现:体外:微球显示(1)无细胞毒性(CCK-8 检测;活/死染色;细胞骨架染色;扫描电子显微镜观察),以及(2)无抑制成骨潜能(碱性磷酸酶活性)。体内:与仅清创对照组(3143±727×10³CFU/g;p<0.0001)相比,M/R-P 微球显著降低了耐甲氧西林金黄色葡萄球菌负担(8±3×10³CFU/g),且感染几乎完全消退(组织病理学)。结论:这些结果表明,M/R-P 微球具有优异的安全性、良好的细胞相容性和显著的抗菌疗效。这些发现证实了我们创新方法的可行性,即通过技术优化联合使用抗生素,将 PLGA 作为慢性骨髓炎局部抗生素治疗的药物递送载体。这为最终克服创伤性骨髓炎的临床挑战提供了一个新的战略方向。

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本文引用的文献

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Efficacy and Safety of 4-Month Rifapentine-Based Tuberculosis Treatments in Persons with Diabetes.基于利福喷汀的4个月结核病治疗方案在糖尿病患者中的疗效与安全性
Emerg Infect Dis. 2025 Mar;31(3):467-476. doi: 10.3201/eid3103.241634.
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Osteomyelitis-relevant antibiotics at clinical concentrations show limited effectivity against acute and chronic intracellular infections in osteocytes.在临床浓度下,与骨髓炎相关的抗生素对破骨细胞内的急性和慢性感染的疗效有限。
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Investigation of the effect of rifampicin resistance and risk factors on recovery rates after DAIR procedure in patients with prosthetic joint infection.
研究利福平耐药性和危险因素对人工关节感染患者 DAIR 术后恢复率的影响。
J Orthop Surg Res. 2023 Aug 21;18(1):611. doi: 10.1186/s13018-023-04091-y.
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A simple method to improve the antibiotic elution profiles from polymethylmethacrylate bone cement spacers by using rapid absorbable sutures.一种通过使用可快速吸收缝线来改善聚甲基丙烯酸甲酯骨水泥间隔物中抗生素洗脱曲线的简单方法。
BMC Musculoskelet Disord. 2022 Oct 14;23(1):916. doi: 10.1186/s12891-022-05870-0.
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A potent antibiotic-loaded bone-cement implant against staphylococcal bone infections.一种强效抗生素载骨水泥植入物,用于治疗葡萄球菌性骨感染。
Nat Biomed Eng. 2022 Oct;6(10):1180-1195. doi: 10.1038/s41551-022-00950-x. Epub 2022 Oct 13.
6
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Bone Res. 2022 Aug 12;10(1):53. doi: 10.1038/s41413-022-00227-8.
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Arch Bone Jt Surg. 2022 Feb;10(2):135-140. doi: 10.22038/abjs.2021.53590.2665.
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