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Animal models of chronic wound care: the application of biofilms in clinical research

Authors Trøstrup H, Thomsen K, Calum H, Høiby N, Moser C

Received 31 March 2016

Accepted for publication 15 June 2016

Published 1 November 2016 Volume 2016:3 Pages 123—132

DOI https://doi.org/10.2147/CWCMR.S84361

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 4

Editor who approved publication: Professor Marco Romanelli


Hannah Trøstrup,1 Kim Thomsen,1 Henrik Calum,2 Niels Høiby,1,3 Claus Moser1

1Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, 2Department of Clinical Microbiology, Copenhagen University Hospital, Hvidovre, 3Institute for Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark

Abstract: Chronic wounds are a substantial clinical problem affecting millions of people worldwide. Pathophysiologically, chronic wounds are stuck in the inflammatory state of healing. The role of bacterial biofilms in suppression and perturbation of host response could be an explanation for this observation. An inhibiting effect of bacterial biofilms on wound healing is gaining significant clinical attention over the last few years. There is still a paucity of suitable animal models to recapitulate human chronic wounds. The etiology of the wound (venous insufficiency, ischemia, diabetes, pressure) has to be taken into consideration as underlying pathophysiological mechanisms and comorbidities display tremendous variation in humans. Confounders such as infection, smoking, chronological age, sex, medication, metabolic disturbances, and renal impairment add to the difficulty in gaining systematic and comparable studies on nonhealing wounds. Relevant hypotheses based on clinical or in vitro observations can be tested in representative animal models, which provide crucial tools to uncover the pathophysiology of cutaneous skin repair in infectious environments. Disposing factors, species of the infectious agent(s), and time of establishment of the infection are well defined in suitable animal models. In addition, several endpoints can be involved for evaluation. Animals do not display chronic wounds in the way that humans do. However, in many cases, animal models can mirror the pathological conditions observed in humans, although discrepancies between human and animal wound repair are obvious. The use of animal models should be refined and replaced whenever possible, and reproducibility and clinical relevance should be strived. This review aimed at giving an overview of the model systems and major findings for inspiration for clinicians and researchers involved in handling chronic nonhealing wounds. Relevant animal models on wound repair are discussed, and our novel wound model on the host/pathogen interplay is presented. In this model, murine wounds are stuck in a polymorphonuclear neutrophil granulocyte-dominated inflammation due to the presence of visually confirmed Pseudomonas aeruginosa biofilm located in the dermis and subcutaneous fatty tissue.

Keywords: pathogen interplay, chronic wound science, Pseudomonas aeruginosa biofilm

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