Development of an implantable three-dimensional model of a functional pathogenic multispecies biofilm to study infected wounds

Abstract Chronic wounds cannot heal due to impairment of regeneration, mainly caused by the persistent infection of multispecies biofilms. Still, the effects of biofilm wound infection and its interaction with the host are not fully described. We aimed to study functional biofilms in physiological c...

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Main Authors: Camila Cárdenas-Calderón, Valentina Veloso-Giménez, Tamara González, Aniela Wozniak, Patricia García, Sebastián San Martín, Juan F. Varas, Ivo Carrasco-Wong, Mario Vera, José Tomás Egaña
Format: Article
Language:English
Published: Nature Portfolio 2022-12-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-25569-5
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author Camila Cárdenas-Calderón
Valentina Veloso-Giménez
Tamara González
Aniela Wozniak
Patricia García
Sebastián San Martín
Juan F. Varas
Ivo Carrasco-Wong
Mario Vera
José Tomás Egaña
author_facet Camila Cárdenas-Calderón
Valentina Veloso-Giménez
Tamara González
Aniela Wozniak
Patricia García
Sebastián San Martín
Juan F. Varas
Ivo Carrasco-Wong
Mario Vera
José Tomás Egaña
author_sort Camila Cárdenas-Calderón
collection DOAJ
description Abstract Chronic wounds cannot heal due to impairment of regeneration, mainly caused by the persistent infection of multispecies biofilms. Still, the effects of biofilm wound infection and its interaction with the host are not fully described. We aimed to study functional biofilms in physiological conditions in vitro, and their potential effects in health and regeneration in vivo. Therefore, Pseudomonas aeruginosa, Staphylococcus aureus and Enterococcus faecalis were seeded in collagen-based scaffolds for dermal regeneration. After 24 h, scaffolds had bacterial loads depending on the initial inoculum, containing viable biofilms with antibiotic tolerance. Afterwards, scaffolds were implanted onto full skin wounds in mice, together with daily supervision and antibiotic treatment. Although all mice survived their health was affected, displaying fever and weight loss. After ten days, histomorphology of scaffolds showed high heterogeneity in samples and within groups. Wounds were strongly, mildly, or not infected according to colony forming units, and P. aeruginosa had higher identification frequency. Biofilm infection induced leucocyte infiltration and elevated interferon-γ and interleukin-10 in scaffolds, increase of size and weight of spleen and high systemic pro-calcitonin concentrations. This functional and implantable 3D biofilm model allows to study host response during infection, providing a useful tool for infected wounds therapy development.
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spelling doaj.art-3f95561078814c1393e594d554575ddf2022-12-22T03:53:25ZengNature PortfolioScientific Reports2045-23222022-12-0112111310.1038/s41598-022-25569-5Development of an implantable three-dimensional model of a functional pathogenic multispecies biofilm to study infected woundsCamila Cárdenas-Calderón0Valentina Veloso-Giménez1Tamara González2Aniela Wozniak3Patricia García4Sebastián San Martín5Juan F. Varas6Ivo Carrasco-Wong7Mario Vera8José Tomás Egaña9Institute for Biological and Medical Engineering, Schools of Engineering, Medicine and Biological Sciences, Pontificia Universidad Católica de ChileInstitute for Biological and Medical Engineering, Schools of Engineering, Medicine and Biological Sciences, Pontificia Universidad Católica de ChileDepartment of Clinical Laboratory, School of Medicine, Pontificia Universidad Católica de ChileDepartment of Clinical Laboratory, School of Medicine, Pontificia Universidad Católica de ChileDepartment of Clinical Laboratory, School of Medicine, Pontificia Universidad Católica de ChileBiomedical Research Center, School of Medicine, Universidad de ValparaísoBiomedical Research Center, School of Medicine, Universidad de ValparaísoCellular Signaling and Differentiation Laboratory (CSDL), School of Medical Technology, Health Sciences Faculty, Universidad San SebastianInstitute for Biological and Medical Engineering, Schools of Engineering, Medicine and Biological Sciences, Pontificia Universidad Católica de ChileInstitute for Biological and Medical Engineering, Schools of Engineering, Medicine and Biological Sciences, Pontificia Universidad Católica de ChileAbstract Chronic wounds cannot heal due to impairment of regeneration, mainly caused by the persistent infection of multispecies biofilms. Still, the effects of biofilm wound infection and its interaction with the host are not fully described. We aimed to study functional biofilms in physiological conditions in vitro, and their potential effects in health and regeneration in vivo. Therefore, Pseudomonas aeruginosa, Staphylococcus aureus and Enterococcus faecalis were seeded in collagen-based scaffolds for dermal regeneration. After 24 h, scaffolds had bacterial loads depending on the initial inoculum, containing viable biofilms with antibiotic tolerance. Afterwards, scaffolds were implanted onto full skin wounds in mice, together with daily supervision and antibiotic treatment. Although all mice survived their health was affected, displaying fever and weight loss. After ten days, histomorphology of scaffolds showed high heterogeneity in samples and within groups. Wounds were strongly, mildly, or not infected according to colony forming units, and P. aeruginosa had higher identification frequency. Biofilm infection induced leucocyte infiltration and elevated interferon-γ and interleukin-10 in scaffolds, increase of size and weight of spleen and high systemic pro-calcitonin concentrations. This functional and implantable 3D biofilm model allows to study host response during infection, providing a useful tool for infected wounds therapy development.https://doi.org/10.1038/s41598-022-25569-5
spellingShingle Camila Cárdenas-Calderón
Valentina Veloso-Giménez
Tamara González
Aniela Wozniak
Patricia García
Sebastián San Martín
Juan F. Varas
Ivo Carrasco-Wong
Mario Vera
José Tomás Egaña
Development of an implantable three-dimensional model of a functional pathogenic multispecies biofilm to study infected wounds
Scientific Reports
title Development of an implantable three-dimensional model of a functional pathogenic multispecies biofilm to study infected wounds
title_full Development of an implantable three-dimensional model of a functional pathogenic multispecies biofilm to study infected wounds
title_fullStr Development of an implantable three-dimensional model of a functional pathogenic multispecies biofilm to study infected wounds
title_full_unstemmed Development of an implantable three-dimensional model of a functional pathogenic multispecies biofilm to study infected wounds
title_short Development of an implantable three-dimensional model of a functional pathogenic multispecies biofilm to study infected wounds
title_sort development of an implantable three dimensional model of a functional pathogenic multispecies biofilm to study infected wounds
url https://doi.org/10.1038/s41598-022-25569-5
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