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 (...

Full description

Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2024-03-01
Series:Biomedicine & Pharmacotherapy
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0753332224001094
_version_ 1797291863210721280
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
format Article
id doaj.art-d9a8ffab328e4211947080f810e6f352
institution Directory Open Access Journal
issn 0753-3322
language English
last_indexed 2024-03-07T19:43:53Z
publishDate 2024-03-01
publisher Elsevier
record_format Article
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
work_keys_str_mv AT alimukeremu 3dprintedplgascaffoldwithnanohydroxyapatitecarryinglinezolidfortreatmentofinfectedbonedefects
AT zhilinliang 3dprintedplgascaffoldwithnanohydroxyapatitecarryinglinezolidfortreatmentofinfectedbonedefects
AT linlinchen 3dprintedplgascaffoldwithnanohydroxyapatitecarryinglinezolidfortreatmentofinfectedbonedefects
AT aikebaiertuxun 3dprintedplgascaffoldwithnanohydroxyapatitecarryinglinezolidfortreatmentofinfectedbonedefects
AT maimaitiailiabulikemu 3dprintedplgascaffoldwithnanohydroxyapatitecarryinglinezolidfortreatmentofinfectedbonedefects
AT yuanquanwu 3dprintedplgascaffoldwithnanohydroxyapatitecarryinglinezolidfortreatmentofinfectedbonedefects