Unravelling host-pathogen interactions by biofilm infected human wound models
Approximately 80 % of persistent wound infections are affected by the presence of bacterial biofilms, resulting in a severe clinical challenge associated with prolonged healing periods, increased morbidity, and high healthcare costs. Unfortunately, in vitro models for wound infection research almost...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Biofilm |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590207523000618 |
| _version_ | 1797385081915965440 |
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| author | Jana Wächter Pia K. Vestweber Viktoria Planz Maike Windbergs |
| author_facet | Jana Wächter Pia K. Vestweber Viktoria Planz Maike Windbergs |
| author_sort | Jana Wächter |
| collection | DOAJ |
| description | Approximately 80 % of persistent wound infections are affected by the presence of bacterial biofilms, resulting in a severe clinical challenge associated with prolonged healing periods, increased morbidity, and high healthcare costs. Unfortunately, in vitro models for wound infection research almost exclusively focus on early infection stages with planktonic bacteria. In this study, we present a new approach to emulate biofilm-infected human wounds by three-dimensional human in vitro systems. For this purpose, a matured biofilm consisting of the clinical key wound pathogen Pseudomonas aeruginosa was pre-cultivated on electrospun scaffolds allowing for non-destructive transfer of the matured biofilm to human in vitro wound models. We infected tissue-engineered human in vitro skin models as well as ex vivo human skin explants with the biofilm and analyzed structural tissue characteristics, biofilm growth behavior, and biofilm-tissue interactions. The structural development of biofilms in close proximity to the tissue, resulting in high bacterial burden and in vivo-like morphology, confirmed a manifest wound infection on all tested wound models, validating their applicability for general investigations of biofilm growth and structure. The extent of bacterial colonization of the wound bed, as well as the subsequent changes in molecular composition of skin tissue, were inherently linked to the characteristics of the underlying wound models including their viability and origin. Notably, the immune response observed in viable ex vivo and in vitro models was consistent with previous in vivo reports. While ex vivo models offered greater complexity and closer similarity to the in vivo conditions, in vitro models consistently demonstrated higher reproducibility. As a consequence, when focusing on direct biofilm-skin interactions, the viability of the wound models as well as their advantages and limitations should be aligned to the particular research question of future studies. Altogether, the novel model allows for a systematic investigation of host-pathogen interactions of bacterial biofilms and human wound tissue, also paving the way for development and predictive testing of novel therapeutics to combat biofilm-infected wounds. |
| first_indexed | 2024-03-08T21:49:01Z |
| format | Article |
| id | doaj.art-4e6b6a0f34034006a9e2a4535d942296 |
| institution | Directory Open Access Journal |
| issn | 2590-2075 |
| language | English |
| last_indexed | 2024-03-08T21:49:01Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biofilm |
| spelling | doaj.art-4e6b6a0f34034006a9e2a4535d9422962023-12-20T07:36:47ZengElsevierBiofilm2590-20752023-12-016100164Unravelling host-pathogen interactions by biofilm infected human wound modelsJana Wächter0Pia K. Vestweber1Viktoria Planz2Maike Windbergs3Institute of Pharmaceutical Technology, Goethe University Frankfurt, Frankfurt am Main, GermanyInstitute of Pharmaceutical Technology, Goethe University Frankfurt, Frankfurt am Main, GermanyInstitute of Pharmaceutical Technology, Goethe University Frankfurt, Frankfurt am Main, GermanyCorresponding author. Institute of Pharmaceutical Technology, Goethe University Frankfurt, Max-von-Laue-Str. 9, 60438, Frankfurt am Main, Germany.; Institute of Pharmaceutical Technology, Goethe University Frankfurt, Frankfurt am Main, GermanyApproximately 80 % of persistent wound infections are affected by the presence of bacterial biofilms, resulting in a severe clinical challenge associated with prolonged healing periods, increased morbidity, and high healthcare costs. Unfortunately, in vitro models for wound infection research almost exclusively focus on early infection stages with planktonic bacteria. In this study, we present a new approach to emulate biofilm-infected human wounds by three-dimensional human in vitro systems. For this purpose, a matured biofilm consisting of the clinical key wound pathogen Pseudomonas aeruginosa was pre-cultivated on electrospun scaffolds allowing for non-destructive transfer of the matured biofilm to human in vitro wound models. We infected tissue-engineered human in vitro skin models as well as ex vivo human skin explants with the biofilm and analyzed structural tissue characteristics, biofilm growth behavior, and biofilm-tissue interactions. The structural development of biofilms in close proximity to the tissue, resulting in high bacterial burden and in vivo-like morphology, confirmed a manifest wound infection on all tested wound models, validating their applicability for general investigations of biofilm growth and structure. The extent of bacterial colonization of the wound bed, as well as the subsequent changes in molecular composition of skin tissue, were inherently linked to the characteristics of the underlying wound models including their viability and origin. Notably, the immune response observed in viable ex vivo and in vitro models was consistent with previous in vivo reports. While ex vivo models offered greater complexity and closer similarity to the in vivo conditions, in vitro models consistently demonstrated higher reproducibility. As a consequence, when focusing on direct biofilm-skin interactions, the viability of the wound models as well as their advantages and limitations should be aligned to the particular research question of future studies. Altogether, the novel model allows for a systematic investigation of host-pathogen interactions of bacterial biofilms and human wound tissue, also paving the way for development and predictive testing of novel therapeutics to combat biofilm-infected wounds.http://www.sciencedirect.com/science/article/pii/S2590207523000618Bacterial biofilmsIn vitro skin infection modelHost-biofilm interactionsPersistent wound infectionsInnate immune response |
| spellingShingle | Jana Wächter Pia K. Vestweber Viktoria Planz Maike Windbergs Unravelling host-pathogen interactions by biofilm infected human wound models Biofilm Bacterial biofilms In vitro skin infection model Host-biofilm interactions Persistent wound infections Innate immune response |
| title | Unravelling host-pathogen interactions by biofilm infected human wound models |
| title_full | Unravelling host-pathogen interactions by biofilm infected human wound models |
| title_fullStr | Unravelling host-pathogen interactions by biofilm infected human wound models |
| title_full_unstemmed | Unravelling host-pathogen interactions by biofilm infected human wound models |
| title_short | Unravelling host-pathogen interactions by biofilm infected human wound models |
| title_sort | unravelling host pathogen interactions by biofilm infected human wound models |
| topic | Bacterial biofilms In vitro skin infection model Host-biofilm interactions Persistent wound infections Innate immune response |
| url | http://www.sciencedirect.com/science/article/pii/S2590207523000618 |
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