3D printed PLGA scaffold with nano-hydroxyapatite carrying linezolid for treatment of infected bone defects
Background: Linezolid has been reported to protect against chronic bone and joint infection. In this study, linezolid was loaded into the 3D printed poly (lactic-co-glycolic acid) (PLGA) scaffold with nano-hydroxyapatite (HA) to explore the effect of this composite scaffold on infected bone defect (...
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Elsevier
2024-03-01
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Series: | Biomedicine & Pharmacotherapy |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332224001094 |
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author | A.li mu Ke re mu Zhi lin Liang Linlin Chen Ai ke bai er Tu xun Mai mai ti ai li A bu li ke mu Yuan quan Wu |
author_facet | A.li mu Ke re mu Zhi lin Liang Linlin Chen Ai ke bai er Tu xun Mai mai ti ai li A bu li ke mu Yuan quan Wu |
author_sort | A.li mu Ke re mu |
collection | DOAJ |
description | Background: Linezolid has been reported to protect against chronic bone and joint infection. In this study, linezolid was loaded into the 3D printed poly (lactic-co-glycolic acid) (PLGA) scaffold with nano-hydroxyapatite (HA) to explore the effect of this composite scaffold on infected bone defect (IBD). Methods: PLGA scaffolds were produced using the 3D printing method. Drug release of linezolid was analyzed by elution and high-performance liquid chromatography assay. PLGA, PLGA-HA, and linezolid-loaded PLGA-HA scaffolds, were implanted into the defect site of a rabbit radius defect model. Micro-CT, H&E, and Masson staining, and immunohistochemistry were performed to analyze bone infection and bone healing. Evaluation of viable bacteria was performed. The cytocompatibility of 3D-printed composite scaffolds in vitro was detected using human bone marrow mesenchymal stem cells (BMSCs). Long-term safety of the scaffolds in rabbits was evaluated. Results: The linezolid-loaded PLGA-HA scaffolds exhibited a sustained release of linezolid and showed significant antibacterial effects. In the IBD rabbit models implanted with the scaffolds, the linezolid-loaded PLGA-HA scaffolds promoted bone healing and attenuated bone infection. The PLGA-HA scaffolds carrying linezolid upregulated the expression of osteogenic genes including collagen I, runt-related transcription factor 2, and osteocalcin. The linezolid-loaded PLGA-HA scaffolds promoted the proliferation and osteogenesis of BMSCs in vitro via the PI3K/AKT pathway. Moreover, the rabbits implanted with the linezolid-loaded scaffolds showed normal biochemical profiles and normal histology, which suggested the safety of the linezolid-loaded scaffolds. Conclusion: Overall, the linezolid-loaded PLGA-HA scaffolds fabricated by 3D printing exerts significant bone repair and anti-infection effects. |
first_indexed | 2024-03-07T19:43:53Z |
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institution | Directory Open Access Journal |
issn | 0753-3322 |
language | English |
last_indexed | 2024-03-07T19:43:53Z |
publishDate | 2024-03-01 |
publisher | Elsevier |
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series | Biomedicine & Pharmacotherapy |
spelling | doaj.art-d9a8ffab328e4211947080f810e6f3522024-02-29T05:17:48ZengElsevierBiomedicine & Pharmacotherapy0753-33222024-03-011721162283D printed PLGA scaffold with nano-hydroxyapatite carrying linezolid for treatment of infected bone defectsA.li mu Ke re mu0Zhi lin Liang1Linlin Chen2Ai ke bai er Tu xun3Mai mai ti ai li A bu li ke mu4Yuan quan Wu5Orthopedics Center, First People's Hospital of Kashgar, Kashgar 844000, Xinjiang, ChinaOrthopedics Center, First People's Hospital of Kashgar, Kashgar 844000, Xinjiang, ChinaNanjing Genebios Biotechnology Co., Ltd., Nanjing 21100, ChinaOrthopedics Center, First People's Hospital of Kashgar, Kashgar 844000, Xinjiang, ChinaOrthopedics Center, First People's Hospital of Kashgar, Kashgar 844000, Xinjiang, China; Correspondence to: First People's Hospital of Kashgar, 120 Yingbin Road, Kashgar 844000, Xinjiang, PR ChinaOrthopedics Center, First People's Hospital of Kashgar, Kashgar 844000, Xinjiang, China; Correspondence to: First People's Hospital of Kashgar, 120 Yingbin Road, Kashgar 844000, Xinjiang, PR ChinaBackground: Linezolid has been reported to protect against chronic bone and joint infection. In this study, linezolid was loaded into the 3D printed poly (lactic-co-glycolic acid) (PLGA) scaffold with nano-hydroxyapatite (HA) to explore the effect of this composite scaffold on infected bone defect (IBD). Methods: PLGA scaffolds were produced using the 3D printing method. Drug release of linezolid was analyzed by elution and high-performance liquid chromatography assay. PLGA, PLGA-HA, and linezolid-loaded PLGA-HA scaffolds, were implanted into the defect site of a rabbit radius defect model. Micro-CT, H&E, and Masson staining, and immunohistochemistry were performed to analyze bone infection and bone healing. Evaluation of viable bacteria was performed. The cytocompatibility of 3D-printed composite scaffolds in vitro was detected using human bone marrow mesenchymal stem cells (BMSCs). Long-term safety of the scaffolds in rabbits was evaluated. Results: The linezolid-loaded PLGA-HA scaffolds exhibited a sustained release of linezolid and showed significant antibacterial effects. In the IBD rabbit models implanted with the scaffolds, the linezolid-loaded PLGA-HA scaffolds promoted bone healing and attenuated bone infection. The PLGA-HA scaffolds carrying linezolid upregulated the expression of osteogenic genes including collagen I, runt-related transcription factor 2, and osteocalcin. The linezolid-loaded PLGA-HA scaffolds promoted the proliferation and osteogenesis of BMSCs in vitro via the PI3K/AKT pathway. Moreover, the rabbits implanted with the linezolid-loaded scaffolds showed normal biochemical profiles and normal histology, which suggested the safety of the linezolid-loaded scaffolds. Conclusion: Overall, the linezolid-loaded PLGA-HA scaffolds fabricated by 3D printing exerts significant bone repair and anti-infection effects.http://www.sciencedirect.com/science/article/pii/S0753332224001094LinezolidPLGA-HAScaffoldsBone defectsBone regenerationInfection |
spellingShingle | A.li mu Ke re mu Zhi lin Liang Linlin Chen Ai ke bai er Tu xun Mai mai ti ai li A bu li ke mu Yuan quan Wu 3D printed PLGA scaffold with nano-hydroxyapatite carrying linezolid for treatment of infected bone defects Biomedicine & Pharmacotherapy Linezolid PLGA-HA Scaffolds Bone defects Bone regeneration Infection |
title | 3D printed PLGA scaffold with nano-hydroxyapatite carrying linezolid for treatment of infected bone defects |
title_full | 3D printed PLGA scaffold with nano-hydroxyapatite carrying linezolid for treatment of infected bone defects |
title_fullStr | 3D printed PLGA scaffold with nano-hydroxyapatite carrying linezolid for treatment of infected bone defects |
title_full_unstemmed | 3D printed PLGA scaffold with nano-hydroxyapatite carrying linezolid for treatment of infected bone defects |
title_short | 3D printed PLGA scaffold with nano-hydroxyapatite carrying linezolid for treatment of infected bone defects |
title_sort | 3d printed plga scaffold with nano hydroxyapatite carrying linezolid for treatment of infected bone defects |
topic | Linezolid PLGA-HA Scaffolds Bone defects Bone regeneration Infection |
url | http://www.sciencedirect.com/science/article/pii/S0753332224001094 |
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