Activated Polyhydroxyalkanoate Meshes Prevent Bacterial Adhesion and Biofilm Development in Regenerative Medicine Applications

Regenerative medicine has become an extremely valuable tool offering an alternative to conventional therapies for the repair and regeneration of tissues. The re-establishment of tissue and organ functions can be carried out by tissue engineering strategies or by using medical devices such as implant...

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Main Authors: Sheila Piarali, Lennart Marlinghaus, Richard Viebahn, Helen Lewis, Maxim G. Ryadnov, Jürgen Groll, Jochen Salber, Ipsita Roy
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-05-01
Series:Frontiers in Bioengineering and Biotechnology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fbioe.2020.00442/full
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author Sheila Piarali
Sheila Piarali
Lennart Marlinghaus
Richard Viebahn
Helen Lewis
Maxim G. Ryadnov
Jürgen Groll
Jochen Salber
Ipsita Roy
author_facet Sheila Piarali
Sheila Piarali
Lennart Marlinghaus
Richard Viebahn
Helen Lewis
Maxim G. Ryadnov
Jürgen Groll
Jochen Salber
Ipsita Roy
author_sort Sheila Piarali
collection DOAJ
description Regenerative medicine has become an extremely valuable tool offering an alternative to conventional therapies for the repair and regeneration of tissues. The re-establishment of tissue and organ functions can be carried out by tissue engineering strategies or by using medical devices such as implants. However, with any material being implanted inside the human body, one of the conundrums that remains is the ease with which these materials can get contaminated by bacteria. Bacterial adhesion leads to the formation of mature, alive and complex three-dimensional biofilm structures, further infection of surrounding tissues and consequent development of complicated chronic infections. Hence, novel tissue engineering strategies delivering biofilm-targeted therapies, while at the same time allowing tissue formation are highly relevant. In this study our aim was to develop surface modified polyhydroxyalkanoate-based fiber meshes with enhanced bacterial anti-adhesive and juvenile biofilm disrupting properties for tissue regeneration purposes. Using reactive and amphiphilic star-shaped macromolecules as an additive to a polyhydroxyalkanoate spinning solution, a synthetic antimicrobial peptide, Amhelin, with strong bactericidal and anti-biofilm properties, and Dispersin B, an enzyme promoting the disruption of exopolysaccharides found in the biofilm matrix, were covalently conjugated to the fibers by addition to the solution before the spinning process. Staphylococcus epidermidis is one of the most problematic pathogens responsible for tissue-related infections. The initial antibacterial screening showed that Amhelin proved to be strongly bactericidal at 12 μg/ml and caused >50% reductions of biofilm formation at 6 μg/ml, while Dispersin B was found to disperse >70% of pre-formed biofilms at 3 μg/ml. Regarding the cytotoxicity of the agents toward L929 murine fibroblasts, a CC50 of 140 and 115 μg/ml was measured for Amhelin and Dispersin B, respectively. Optimization of the electrospinning process resulted in aligned fibers. Surface activated fibers with Amhelin and Dispersin B resulted in 83% reduction of adhered bacteria on the surface of the fibers. Additionally, the materials developed were found to be cytocompatible toward L929 murine fibroblasts. The strategy reported in this preliminary study suggests an alternative approach to prevent bacterial adhesion and, in turn biofilm formation, in materials used in regenerative medicine applications such as tissue engineering.
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spelling doaj.art-b75b12228c6747caac9e571d993b6bae2022-12-21T22:45:47ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852020-05-01810.3389/fbioe.2020.00442539408Activated Polyhydroxyalkanoate Meshes Prevent Bacterial Adhesion and Biofilm Development in Regenerative Medicine ApplicationsSheila Piarali0Sheila Piarali1Lennart Marlinghaus2Richard Viebahn3Helen Lewis4Maxim G. Ryadnov5Jürgen Groll6Jochen Salber7Ipsita Roy8Department of Surgery, Universitätsklinikum Knappschaftskrankenhaus Bochum, Ruhr-University, Bochum, GermanyApplied Biotechnology Research Group, School of Life Sciences, College of Liberal Arts and Sciences, University of Westminster, London, United KingdomDepartment of Medical Microbiology, Ruhr-University Bochum, Bochum, GermanyDepartment of Surgery, Universitätsklinikum Knappschaftskrankenhaus Bochum, Ruhr-University, Bochum, GermanyNational Physical Laboratory, Teddington, United KingdomNational Physical Laboratory, Teddington, United KingdomDepartment for Functional Materials in Medicine and Dentistry and Bavarian Polymer Institute, University of Würzburg, Würzburg, GermanyDepartment of Surgery, Universitätsklinikum Knappschaftskrankenhaus Bochum, Ruhr-University, Bochum, GermanyDepartment of Material Science and Engineering, Faculty of Engineering, University of Sheffield, Sheffield, United KingdomRegenerative medicine has become an extremely valuable tool offering an alternative to conventional therapies for the repair and regeneration of tissues. The re-establishment of tissue and organ functions can be carried out by tissue engineering strategies or by using medical devices such as implants. However, with any material being implanted inside the human body, one of the conundrums that remains is the ease with which these materials can get contaminated by bacteria. Bacterial adhesion leads to the formation of mature, alive and complex three-dimensional biofilm structures, further infection of surrounding tissues and consequent development of complicated chronic infections. Hence, novel tissue engineering strategies delivering biofilm-targeted therapies, while at the same time allowing tissue formation are highly relevant. In this study our aim was to develop surface modified polyhydroxyalkanoate-based fiber meshes with enhanced bacterial anti-adhesive and juvenile biofilm disrupting properties for tissue regeneration purposes. Using reactive and amphiphilic star-shaped macromolecules as an additive to a polyhydroxyalkanoate spinning solution, a synthetic antimicrobial peptide, Amhelin, with strong bactericidal and anti-biofilm properties, and Dispersin B, an enzyme promoting the disruption of exopolysaccharides found in the biofilm matrix, were covalently conjugated to the fibers by addition to the solution before the spinning process. Staphylococcus epidermidis is one of the most problematic pathogens responsible for tissue-related infections. The initial antibacterial screening showed that Amhelin proved to be strongly bactericidal at 12 μg/ml and caused >50% reductions of biofilm formation at 6 μg/ml, while Dispersin B was found to disperse >70% of pre-formed biofilms at 3 μg/ml. Regarding the cytotoxicity of the agents toward L929 murine fibroblasts, a CC50 of 140 and 115 μg/ml was measured for Amhelin and Dispersin B, respectively. Optimization of the electrospinning process resulted in aligned fibers. Surface activated fibers with Amhelin and Dispersin B resulted in 83% reduction of adhered bacteria on the surface of the fibers. Additionally, the materials developed were found to be cytocompatible toward L929 murine fibroblasts. The strategy reported in this preliminary study suggests an alternative approach to prevent bacterial adhesion and, in turn biofilm formation, in materials used in regenerative medicine applications such as tissue engineering.https://www.frontiersin.org/article/10.3389/fbioe.2020.00442/fullpolyhydroxyalkanoatesAmhelinDispersin Bbiofilmelectrospinning
spellingShingle Sheila Piarali
Sheila Piarali
Lennart Marlinghaus
Richard Viebahn
Helen Lewis
Maxim G. Ryadnov
Jürgen Groll
Jochen Salber
Ipsita Roy
Activated Polyhydroxyalkanoate Meshes Prevent Bacterial Adhesion and Biofilm Development in Regenerative Medicine Applications
Frontiers in Bioengineering and Biotechnology
polyhydroxyalkanoates
Amhelin
Dispersin B
biofilm
electrospinning
title Activated Polyhydroxyalkanoate Meshes Prevent Bacterial Adhesion and Biofilm Development in Regenerative Medicine Applications
title_full Activated Polyhydroxyalkanoate Meshes Prevent Bacterial Adhesion and Biofilm Development in Regenerative Medicine Applications
title_fullStr Activated Polyhydroxyalkanoate Meshes Prevent Bacterial Adhesion and Biofilm Development in Regenerative Medicine Applications
title_full_unstemmed Activated Polyhydroxyalkanoate Meshes Prevent Bacterial Adhesion and Biofilm Development in Regenerative Medicine Applications
title_short Activated Polyhydroxyalkanoate Meshes Prevent Bacterial Adhesion and Biofilm Development in Regenerative Medicine Applications
title_sort activated polyhydroxyalkanoate meshes prevent bacterial adhesion and biofilm development in regenerative medicine applications
topic polyhydroxyalkanoates
Amhelin
Dispersin B
biofilm
electrospinning
url https://www.frontiersin.org/article/10.3389/fbioe.2020.00442/full
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