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 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.

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Metadaten
Author:Jana WächterORCiD, Pia K. VestweberORCiD, Viktoria Luise PlanzORCiDGND, Maike WindbergsORCiD
URN:urn:nbn:de:hebis:30:3-794823
DOI:https://doi.org/10.1016/j.bioflm.2023.100164
ISSN:2590-2075
Parent Title (English):Biofilm
Publisher:Elsevier
Place of publication:Amsterdam
Document Type:Article
Language:English
Date of Publication (online):2023/11/02
Date of first Publication:2023/11/02
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2024/01/04
Tag:Bacterial biofilms; Host-biofilm interactions; Innate immune response; Persistent wound infections; skin infection model
Volume:2023
Issue:In Press, Journal Pre-proof, 100164
Article Number:100164
Page Number:29
HeBIS-PPN:516370405
Institutes:Biochemie, Chemie und Pharmazie
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - CC BY-NC-ND - Namensnennung - Nicht kommerziell - Keine Bearbeitungen 4.0 International