Systemic and Local Administration of Antimicrobial and Cell Therapies to Prevent Methicillin-Resistant Staphylococcus epidermidis-Induced Femoral Nonunions in a Rat Model

S. epidermidis is responsible for biofilm-related nonunions. This study compares the response to S. epidermidis-infected fractures in rats systemically or locally injected with vancomycin or bone marrow mesenchymal stem cells (BMSCs) in preventing the nonunion establishment. The 50% of rats receivin...

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Main Authors: Arianna B. Lovati, Lorenzo Drago, Marta Bottagisio, Matilde Bongio, Marzia Ferrario, Silvia Perego, Veronica Sansoni, Elena De Vecchi, Carlo L. Romanò
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2016/9595706
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author Arianna B. Lovati
Lorenzo Drago
Marta Bottagisio
Matilde Bongio
Marzia Ferrario
Silvia Perego
Veronica Sansoni
Elena De Vecchi
Carlo L. Romanò
author_facet Arianna B. Lovati
Lorenzo Drago
Marta Bottagisio
Matilde Bongio
Marzia Ferrario
Silvia Perego
Veronica Sansoni
Elena De Vecchi
Carlo L. Romanò
author_sort Arianna B. Lovati
collection DOAJ
description S. epidermidis is responsible for biofilm-related nonunions. This study compares the response to S. epidermidis-infected fractures in rats systemically or locally injected with vancomycin or bone marrow mesenchymal stem cells (BMSCs) in preventing the nonunion establishment. The 50% of rats receiving BMSCs intravenously (s-rBMSCs) died after treatment. A higher cytokine trend was measured in BMSCs locally injected rats (l-rBMSCs) at day 3 and in vancomycin systemically injected rats (l-VANC) at day 7 compared to the other groups. At day 14, the highest cytokine values were measured in l-VANC and in l-rBMSCs for IL-10. µCT showed a good bony bridging in s-VANC and excellent both in l-VANC and in l-rBMSCs. The bacterial growth was lower in s-VANC and l-VANC than in l-rBMSCs. Histology demonstrated the presence of new woven bone in s-VANC and a more mature bony bridging was found in l-VANC. The l-rBMSCs showed a poor bony bridging of fibrovascular tissue. Our results could suggest the synergic use of systemic and local injection of vancomycin as an effective treatment to prevent septic nonunions. This study cannot sustain the systemic injection of BMSCs due to high risks, while a deeper insight into local BMSCs immunomodulatory effects is mandatory before developing cell therapies in clinics.
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spelling doaj-art-3e944ccb1eed422a8b76300d6c02a6e12025-02-03T01:10:46ZengWileyMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/95957069595706Systemic and Local Administration of Antimicrobial and Cell Therapies to Prevent Methicillin-Resistant Staphylococcus epidermidis-Induced Femoral Nonunions in a Rat ModelArianna B. Lovati0Lorenzo Drago1Marta Bottagisio2Matilde Bongio3Marzia Ferrario4Silvia Perego5Veronica Sansoni6Elena De Vecchi7Carlo L. Romanò8Cell and Tissue Engineering Laboratory, IRCCS Galeazzi Orthopaedic Institute, 20161 Milan, ItalyLaboratory of Clinical Chemistry and Microbiology, IRCCS Galeazzi Orthopaedic Institute, 20161 Milan, ItalyCell and Tissue Engineering Laboratory, IRCCS Galeazzi Orthopaedic Institute, 20161 Milan, ItalyCell and Tissue Engineering Laboratory, IRCCS Galeazzi Orthopaedic Institute, 20161 Milan, ItalyMAP Laboratory, Fondazione Filarete, 20139 Milan, ItalyLaboratory of Experimental Biochemistry & Molecular Biology, IRCCS Galeazzi Orthopaedic Institute, 20161 Milan, ItalyLaboratory of Experimental Biochemistry & Molecular Biology, IRCCS Galeazzi Orthopaedic Institute, 20161 Milan, ItalyLaboratory of Clinical Chemistry and Microbiology, IRCCS Galeazzi Orthopaedic Institute, 20161 Milan, ItalyDepartment of Reconstructive Surgery of Osteoarticular Infections, CRIO Unit, IRCCS Galeazzi Orthopaedic Institute, 20161 Milan, ItalyS. epidermidis is responsible for biofilm-related nonunions. This study compares the response to S. epidermidis-infected fractures in rats systemically or locally injected with vancomycin or bone marrow mesenchymal stem cells (BMSCs) in preventing the nonunion establishment. The 50% of rats receiving BMSCs intravenously (s-rBMSCs) died after treatment. A higher cytokine trend was measured in BMSCs locally injected rats (l-rBMSCs) at day 3 and in vancomycin systemically injected rats (l-VANC) at day 7 compared to the other groups. At day 14, the highest cytokine values were measured in l-VANC and in l-rBMSCs for IL-10. µCT showed a good bony bridging in s-VANC and excellent both in l-VANC and in l-rBMSCs. The bacterial growth was lower in s-VANC and l-VANC than in l-rBMSCs. Histology demonstrated the presence of new woven bone in s-VANC and a more mature bony bridging was found in l-VANC. The l-rBMSCs showed a poor bony bridging of fibrovascular tissue. Our results could suggest the synergic use of systemic and local injection of vancomycin as an effective treatment to prevent septic nonunions. This study cannot sustain the systemic injection of BMSCs due to high risks, while a deeper insight into local BMSCs immunomodulatory effects is mandatory before developing cell therapies in clinics.http://dx.doi.org/10.1155/2016/9595706
spellingShingle Arianna B. Lovati
Lorenzo Drago
Marta Bottagisio
Matilde Bongio
Marzia Ferrario
Silvia Perego
Veronica Sansoni
Elena De Vecchi
Carlo L. Romanò
Systemic and Local Administration of Antimicrobial and Cell Therapies to Prevent Methicillin-Resistant Staphylococcus epidermidis-Induced Femoral Nonunions in a Rat Model
Mediators of Inflammation
title Systemic and Local Administration of Antimicrobial and Cell Therapies to Prevent Methicillin-Resistant Staphylococcus epidermidis-Induced Femoral Nonunions in a Rat Model
title_full Systemic and Local Administration of Antimicrobial and Cell Therapies to Prevent Methicillin-Resistant Staphylococcus epidermidis-Induced Femoral Nonunions in a Rat Model
title_fullStr Systemic and Local Administration of Antimicrobial and Cell Therapies to Prevent Methicillin-Resistant Staphylococcus epidermidis-Induced Femoral Nonunions in a Rat Model
title_full_unstemmed Systemic and Local Administration of Antimicrobial and Cell Therapies to Prevent Methicillin-Resistant Staphylococcus epidermidis-Induced Femoral Nonunions in a Rat Model
title_short Systemic and Local Administration of Antimicrobial and Cell Therapies to Prevent Methicillin-Resistant Staphylococcus epidermidis-Induced Femoral Nonunions in a Rat Model
title_sort systemic and local administration of antimicrobial and cell therapies to prevent methicillin resistant staphylococcus epidermidis induced femoral nonunions in a rat model
url http://dx.doi.org/10.1155/2016/9595706
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